Deep vein thrombosis medical therapy: Difference between revisions

Jump to navigation Jump to search
No edit summary
 
(130 intermediate revisions by 10 users not shown)
Line 1: Line 1:
__NOTOC__
__NOTOC__
'''Editor(s)-In-Chief:''' {{ATI}}, [[C. Michael Gibson, M.S., M.D.]] [mailto:mgibson@perfuse.org]; '''Associate Editor(s)-In-Chief:''' {{CZ}} ; [[User:Kashish Goel|Kashish Goel, M.D.]]; '''Assistant Editor(s)-In-Chief:''' [[User:Justine Cadet|Justine Cadet]]


'''To go back to the wikidoc page on [[VTE]], [[Venous thromboembolism|click here]]'''
{| class="infobox" style="float:right;"
|-
| [[File:Siren.gif|30px|link=Deep vein thrombosis resident survival guide]]|| <br> || <br>
| [[Deep vein thrombosis resident survival guide|'''Resident'''<br>'''Survival'''<br>'''Guide''']]
|}
'''Editor(s)-In-Chief:''' {{ATI}}, [[C. Michael Gibson, M.S., M.D.]] [mailto:charlesmichaelgibson@gmail.com]; '''Associate Editor(s)-In-Chief:''' {{CZ}} ; [[User:Kashish Goel|Kashish Goel, M.D.]]; {{Rim}}; {{HK}} '''Assistant Editor(s)-In-Chief:''' [[User:Justine Cadet|Justine Cadet]]
{{Deep vein thrombosis}}
{{Deep vein thrombosis}}
'''For the algorithms about the treatment choices, click [[Deep vein thrombosis treatment approach|here]].'''


==Overview==
==Overview==
An approach to the treatment of [[DVT]] has been described '''[[Deep vein thrombosis treatment algorithm|here]]'''. The primary purpose of treatment is to prevent the following:
[[Clinical practice guideline]]s by the [[American College of Chest Physicians]] guide management.<ref name="pmid26867832">{{cite journal| author=Kearon C, Akl EA, Ornelas J, Blaivas A, Jimenez D, Bounameaux H et al.| title=Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. | journal=Chest | year= 2016 | volume= 149 | issue= 2 | pages= 315-52 | pmid=26867832 | doi=10.1016/j.chest.2015.11.026 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26867832  }} </ref>
* Further clot extension,
 
* Acute Pulmonary embolism,
Anticoagulation therapy is the mainstay of the treatment of deep vein thrombosis (DVT). The medical treatment of DVT consists of an initial parenteral anticoagulation therapy and a long term [[anticoagulation therapy]]. The primary purpose of treatment is to prevent further clot extension, acute [[pulmonary embolism]], recurrence of [[thrombosis]], and late complications such as [[post-thrombotic syndrome]] and chronic thromboembolic [[pulmonary hypertension]].  The treatment of DVT with parental anticoagulation should be initiated in case of intermediate or high suspicion of suspected DVT even before the diagnostic confirmatory tests are complete.  The choice of parental anticoagulation include: low molecular weight heparin (LMWH), fondaparinux, IV unfractionated heparin (UFH) and SC-UFH; however, the administration of LMWH (once daily rather than twice daily) and fondaparinux is recommended over IV-UFH and SCUFH.  Parental anticoagulation therapy should be administered for at least 5 days and until the INR is equal or more than 2 for more than 24 hours.  Patients who receive long term therapy with [[anticoagulation]] should be assessed regularly for the risks vs benefits of [[anticoagulation therapy]].<ref name="pmid22315268">{{cite journal| author=Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ et al.| title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. | journal=Chest | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e419S-94S | pmid=22315268 | doi=10.1378/chest.11-2301 | pmc=PMC3278049 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315268  }} </ref>  An abnormal [[D-dimer]] level at the end of treatment may signal the need for continued treatment in patients with their first unprovoked proximal DVT.<ref name="pmid17065639">{{cite journal| author=Palareti G, Cosmi B, Legnani C, Tosetto A, Brusi C, Iorio A et al.| title=D-dimer testing to determine the duration of anticoagulation therapy. | journal=N Engl J Med | year= 2006 | volume= 355 | issue= 17 | pages= 1780-9 | pmid=17065639 |doi=10.1056/NEJMoa054444 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17065639  }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17400637 Review in: Evid Based Med. 2007 Apr;12(2):45] [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17335152 Review in: ACP J Club. 2007 Mar-Apr;146(2):29] </ref>
* Recurrence of thrombosis,
 
* Prevention of late complications such as:
==Parenteral Anticoagulation Therapy==
** [[Post-thrombotic syndrome]]
===Heparin ===
** Chronic thromboembolic pulmonary hypertension.
* Heparin binds to the enzyme inhibitor antithrombin III (AT).  The activated AT then inactivates thrombin and other proteases involved in blood clotting, most notably [[factor Xa]].
 
* The side effects of heparin include [[bleeding]], [[heparin-induced thrombocytopenia]] and [[osteoporosis]].<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest |volume=141 |issue=2 Suppl |pages=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>  In patients with suspected or confirmed [[heparin-induced thrombocytopenia]], [[lepirudin]] or [[argatroban]] should be used.


== Key Guidelines for Thrombolytic Therapy : ACCP Guidelines ==
* The anticoagulant effects of [[heparin]] can be reversed with IV [[protamine sulfate]].<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest |volume=141 |issue=2 Suppl |pages=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>


; Extensive iliofemoral DVT
====Heparin Dosage====
Shown below is a table depicting the dosage of heparin for the treatment of [[DVT]].  Note that the dose of heparin used in the treatment of [[acute coronary syndrome]] is lower than that used for the treatment of PE.<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest |volume=141 |issue=2 Suppl |pages=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>


{| class="wikitable"
{| style="cellpadding=0; cellspacing= 0; width: 600px;"
|-
| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 30%" align="center" | '''Mode of administration of Heparin'''|| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 70%" align="center" | '''Dosage'''
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align="left" |'''''IV injection'''''
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align="left" |80 U/kg as bolus, followed by 18 U/kg/h, OR <br><br>
70 U/kg as bolus, followed by 15 U/kg/h for stroke or cardiac patients<ref name="pmid22315259">{{cite journal| author=Holbrook A, Schulman S, Witt DM, Vandvik PO, Fish J, Kovacs MJ et al.| title=Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. | journal=Chest | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e152S-84S | pmid=22315259 | doi=10.1378/chest.11-2295 | pmc=PMC3278055 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315259  }} </ref>
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align="left" |'''''SC injection'''''
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align="left" |333 U/kg as bolus, followed by 250 U/kg<ref name="pmid22315259">{{cite journal| author=Holbrook A, Schulman S, Witt DM, Vandvik PO, Fish J, Kovacs MJ et al.| title=Evidence-based management of anticoag
ulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. | journal=Chest | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e152S-84S | pmid=22315259 | doi=10.1378/chest.11-2295 | pmc=PMC3278055 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315259  }} </ref>
|}
 
====Adjustment of Heparin Dosage According to aPTT====
aPTT should be monitored during treatment with [[heparin]].  Prolongation of apTT correlates with an elevated serum concentration  of [[heparin]] and requires adjustment of the dosage.  Shown below is a table depicting the variation in the dosage according the aPTT.
 
{| style="cellpadding=0; cellspacing= 0; width: 600px;"
|-
| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 30%" align="center" | '''aPTT'''|| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 70%" align="center" | '''Variation in the dosage'''<ref name="pmid18757870">{{cite journal| author=Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P et al.| title=Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). | journal=Eur Heart J | year= 2008 | volume= 29 | issue= 18 | pages= 2276-315 | pmid=18757870 | doi=10.1093/eurheartj/ehn310 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18757870  }} </ref>
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align="left" | '''< 1.2 x control (<35 s)'''|| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align="left" | Bolus: 80 U/kg <br> Infusion rate: increase by 4 U/kg/h
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align="left" | '''1.2-1.5 x control (35-45 s)'''|| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align="left" |Bolus: 40 U/kg <br> Infusion rate: increase by 2 U/kg/h
|-
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|Class II Recommendations
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align="left" | '''1.5-2.3 x control (46-70 s)'''|| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align="left" | Continue the same dosage
|-
|-
| bgcolor="LemonChiffon"|
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align="left" | '''2.3-3.0 x control (71-90 s)'''|| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align="left" | Infusion rate: decrease by 2 U/kg/h
* Catheter directed thrombolysis. (Grade C recommendation)
** It is preferred over open throbectomy.(Grade C recommendation)
** Systemic thrombolytics may be useful.(Grade C recommendation)
|-
|-
| bgcolor="LemonChiffon"|* Mechanical thrombectomy to shorten lytic exposure.(Grade C recommendation)
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align="left" | '''> 3.0 x control (>90s)'''|| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align="left" | Stop infusion for a period of 1 hour, then<br>Infusion rate: decrease by 3 U/kg/h
|-
|-
| bgcolor="LemonChiffon"|* PTA/Stenting to relief underlying venous lesion.(Grade C recommendation)
|}
|}


==Anticoagulation==
====Platelet Monitoring====
{{main|Anticoagulation}}
Among patients started on [[heparin]], if the risk of [[heparin induced thrombocytopenia]] is more than 1%, monitor [[platelet count]] every 2 to 3 days from the 4th until the 14th day of treatment or until the discontinuation of [[heparin]].<ref name="pmid22315268">{{cite journal| author=Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ et al.| title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. | journal=Chest | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e419S-94S | pmid=22315268 | doi=10.1378/chest.11-2301 | pmc=PMC3278049 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315268 }} </ref>
[[Anticoagulation]] is "treatment of choice" for DVT. An abnormal [[D-dimer]] level at the end of treatment may signal the need for continued treatment, in patients with first unprovoked proximal [[deep-vein thrombosis]].<ref name="pmid17065639">{{cite journal| author=Palareti G, Cosmi B, Legnani C, Tosetto A, Brusi C, Iorio A et al.| title=D-dimer testing to determine the duration of anticoagulation therapy. | journal=N Engl J Med | year= 2006 | volume= 355 | issue= 17 | pages= 1780-9 | pmid=17065639 |doi=10.1056/NEJMoa054444 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17065639 }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17400637 Review in: Evid Based Med. 2007 Apr;12(2):45] [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17335152 Review in: ACP J Club. 2007 Mar-Apr;146(2):29] </ref> After diagnosis, the current approach is to start both heparin and warfarin (VKA) , and to discontinue heparin after 5 days provided the international normalized ratio (INR) is ≥ 2.0 for at least 24 h.<ref name="pmid18574272">{{cite journal |author=Kearon C, Kahn SR, Agnelli G, Goldhaber S, Raskob GE, Comerota AJ|title=Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) |journal=Chest |volume=133 |issue=6 Suppl|pages=454S–545S |year=2008 |month=June |pmid=18574272|doi=10.1378/chest.08-0658 |url=http://www.chestjournal.org/cgi/pmidlookup?view=long&pmid=18574272 |accessdate=2012-01-11}}</ref>                 
===Parenteral Anticoagulants===
<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest|volume=141 |issue=2 Suppl |pages=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>


====[[Heparin]]====
=== Low Molecular Weight Heparin ===
* Heparin binds to antithrombin and inactivates thrombin, factors IIa, Xa, IXa, XIa and XIIa; binds to heparin cofactor II and inactivates factor IIa; and binds to factor IXa and inhibits factor X activation.
* [[LMWH]] is used as a first line therapy for the initial anticoagulation therapy for DVT.<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest |volume=141 |issue=2 Suppl |pages=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>
* Unfractionated heparin is mainly used in patients with known renal insufficiency or those who need close monitoring for bleeding, as activated partial thromboplastin time can be checked every 2 hours and doses adjusted.
* The apparent biologic half-life of heparin increases from approximately 30 min after an IV bolus of 25 units/kg, to 60 min with an IV bolus of 100 units/kg, to 150 min with a bolus of 400 units/kg.
* Efficacy of heparin in the initial treatment of [[DVT]] or [[PE]] is highly dependent on dosage.
* Initial dosing of IV heparin for VTE is either weight-based (80 units/kg bolus and 18 units/kg/h infusion) or administered as a bolus of 5,000 units followed by an infusion of at least 32,000 units/d, to achieve aPTT value of 1.5-2.5 of the normal value.
* If heparin is given subcutaneously for treatment of VTE, there are at least two options: (1) an initial IV bolus of 5,000 units followed by 250 units/kg twice daily; or (2) an initial subcutaneous dose of 333 units/kg followed by 250 units/kg twice daily thereafter.
* The dose for [[acute coronary syndrome]] is lower as compared to the treatment of [[DVT]]
* The main side effects are heparin-induce thrombocytopenia and osteoporosis.
* One major advantage of heparin is that the anticoagulant effects can be reversed with IV protamine sulfate.


====[[LMWH|Low molecular weight heparin]]====
* In addition, [[LMWH]] can also be used for the long term anticoagulation treatment for DVT, but [[vitamin K antagonist]] are recommended as first line therapy.  However, among cancer patients with provoked PE, [[LMWH]] is the first line therapy for the long term anticoagulation treatment.<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest |volume=141 |issue=2 Suppl |pages=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>  [[LMWH]] is preferred in pregnancy to avoid the known [[teratogenic]] effects of [[warfarin]].  
* [[LMWH]] is administered subcutaneously and is available in various forms like Bemiparin, Dalteparin, Danaparoid, Enoxaparin, Nadroparin, or Tinzaparin.
* The recommended doses for treatment of [[PE]]/[[DVT]] are:
** [[Enoxaparin]] : 1 mg/Kg body weight (twice daily). Dose is 30 mg daily for [[VTE]] prophylaxis.
** [[Tinzaparin]] : 175 U/Kg body weight (once daily).
* The doses in case of renal insufficiency are not clear, except Enoxaparin. It is recommended that the dose of [[Enoxaparin]] should be reduced to 50% of the usual dose in patients with a creatinine clearance of <30 mL/min.


====[[Factor Xa Inhibitor]]====
* [[LMWH]] is administered subcutaneously and does not require routine coagulation monitoring.
<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest |volume=141 |issue=2 Suppl|pages=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>
* [[Fondaparinux]] binds to antithrombin and inhibits factor Xa.
* A fixed dose of 2.5 mg daily is used for thromboprophylaxis. In patients with moderate renal insufficiency (creatinine clearance of 30-50 mL/min), dose should be reduced by 50%.
* Recommended dosages for treatment of [[DVT]] or [[PE]] are:
**Patient weighing <50 Kg (110 lb): 5 mg (once daily).
**Patient weighing 50 Kg (110 lb) to 110 Kg (220 lb): 7.5 mg (once daily).
**Patient weighing >100 Kg (220 lb): 10 mg (once daily).


====Direct thrombin inhibitors====
* The recommended doses for treatment of DVT are:<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest |volume=141 |issue=2 Suppl |pages=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>
<ref name="pmid22315264">{{cite journal |author=Garcia DA, Baglin TP, Weitz JI, Samama MM |title=Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest|volume=141 |issue=2 Suppl|pages=e24S–43S |year=2012 |month=February |pmid=22315264 |doi=10.1378/chest.11-2291 |url=}}</ref>
** [[Enoxaparin]] : 1 mg/Kg body weight (twice daily) OR 1.5 mg/kg once daily
* Direct thrombin inhibitors bind to thrombin and block its activity. These include Hirudin, bivalurudin, and argatroban.
** [[Tinzaparin]] : 175 U/Kg body weight (once daily)


=====Hirudin=====
=== Fondaparinux===
* The recommended dose of IV lepirudin for [[heparin induced thrombocytopenia]] is 0.15 mg/kg/h with or without an initial bolus of 0.4 mg/kg.  
* [[Fondaparinux]] is used as a first line therapy for the initial anticoagulation therapy for DVT. The antithrombotic activity of fondaparinux sodium is the result of antithrombin III (ATIII)-mediated selective inhibition of factor Xa. Fondaparinux does not require routine coagulation monitoring.
* The anticoagulant effect of lepirudin in this setting is monitored by using the aPTT, and the dose is adjusted to achieve a target aPTT ratio of 1.5 to 2.5 times control.
* When given for thromboprophylaxis after elective hip replacement surgery, desirudin is given subcutaneously at a dose of 15 mg twice daily without monitoring.
=====[[Bivalirudin]]=====
* Recommended dose of [[Bivalirudin]] is a bolus of 0.75 mg/kg followed by an infusion of 1.75 mg/kg/h for the duration of the procedure.
* Dose reduction should be considered in patients with moderate to severe renal impairment.


=====[[Argatroban]]=====
* Recommended doses for the treatment of DVT depend on the weight of the patient:
* Argatroban is used for the treatment and prevention of [[heparin-induced thrombocytopenia]] associated thrombosis and for anticoagulation during percutaneous coronary interventions when heparin is contraindicated because of a recent history of  [[heparin-induced thrombocytopenia]].
** Weight <50 Kg: 5 mg (once daily)
* Argatroban is given as a continuous IV infusion with an initial dose of 1 to 2 m g/kg/min and the dose is adjusted to maintain the aPTT ratio in the 1.5 to 2.5 range.
** Weight between 50 Kg to 100 Kg: 7.5 mg (once daily)
** Weight >100 Kg: 10 mg (once daily)


====Warfarin====
==Oral Anticoagulation Therapy==
{{main|Warfarin}}
* The recommended therapeutic INR during the treatment of [[DVT]] or [[PE]] with warfarin is 2.0-3.0.


====Direct factor Xa inhibitor====
=== Vitamin K Antagonist===
[[Rivaroxaban]] (orally active [[direct factor Xa inhibitor]]) has been evaluated in randomized controlled trials for treatment of [[DVT]]. EINSTEIN-DVT and EINSTEIN-Extension Studies enrolled 3449 patients with DVT and showed that [[rivoraxaban]] was non-inferior to the usual approach (lovenox initially followed by warfarin) in the treatment of [[DVT]]<ref name="pmid21128814">{{cite journal |author=Bauersachs R, Berkowitz SD, Brenner B, ''et al.'' |title=Oral rivaroxaban for symptomatic venous thromboembolism |journal=N. Engl. J. Med. |volume=363 |issue=26 |pages=2499–510 |year=2010 |month=December |pmid=21128814 |doi=10.1056/NEJMoa1007903 |url=}}</ref>. It is not yet approved for treatment of [[DVT]] in US, but FDA will be reviewing this application soon. European Union<refhttp://www.bayer.com/en/news-detail-bayer-group.aspx?newsid=15790</ref> has approved the use of [[rivoraxaban]] for treatment of [[DVT]], however NICE committee in UK<refhttp://www.nelm.nhs.uk/en/NeLM-Area/News/2012---March/13/NICE-issues-preliminary-recommendations-ACD-on-rivaroxaban-for-DVT-treatment-and-the-prevention-of-recurrent-DVT-and-PE-/</ref> has asked for more evidence.
* [[Vitamin K antagonist]] is the first line therapy for long term anticoagulation treatment of DVT.<ref name="pmid22315268">{{cite journal| author=Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ et al.| title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. | journal=Chest | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e419S-94S | pmid=22315268 | doi=10.1378/chest.11-2301 | pmc=PMC3278049 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315268  }} </ref>


==ACCP Guidelines: Recommendations for initial choice of treatment in patients with acute DVT of the leg (DO NOT EDIT)==
* [[Warfarin]] should not be administered in pregnancy and [[LMWH]] should be used instead.
<ref name="pmid22315257">{{cite journal |author=Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ |title=Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=7S–47S |year=2012 |month=February |pmid=22315257 |doi=10.1378/chest.1412S3 |url=}}</ref>
 
{|class="wikitable"
* [[Warfarin]] should be started as soon as possible following the initiation of parenteral anticoagulation therapy, preferably at the same day.  Parenteral anticoagulation therapy should be continued for at least 5 days concomitantly with [[warfarin]] and until INR is ≥ 2 for more than 24 hours.<ref name="pmid22315268">{{cite journal| author=Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ et al.| title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. | journal=Chest | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e419S-94S | pmid=22315268 | doi=10.1378/chest.11-2301 | pmc=PMC3278049 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315268  }} </ref>
 
* [[Warfarin]] is administered as follows:
** Begin with 5 mg [[warfarin]] for 2 days followed by dosing based on the [[INR]].
** Target [[INR]] is 2-3.
** Monitor [[INR]] monthly.
** If the [[INR]] is stable but there is one value 0.5 below or above the target range, continue the same dose and repeat [[INR]] within 1-2 weeks.
* [[NSAID]]s, [[COX2]] selective NSAIDs and some antibiotics should be avoided when [[warfarin]] is administered.<ref name="pmid22315259">{{cite journal| author=Holbrook A, Schulman S, Witt DM, Vandvik PO, Fish J, Kovacs MJ et al.| title=Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. | journal=Chest | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e152S-84S | pmid=22315259 | doi=10.1378/chest.11-2295 | pmc=PMC3278055 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315259  }} </ref>
 
===Factor X Inhibitors===
[[Rivaroxaban]] is an oral factor X inhibitors that can be used in the long term treatment of DVT.
 
=== Direct Thrombin Inhibitors===
[[Dabigatran]] is an oral [[direct thrombin inhibitor]]s that can be used in the long term treatment of DVT.
 
==Thrombolysis==
'''''Thrombolysis can refer to either systemic thrombolysis or [[catheter directed thrombolysis]].  To read more about [[catheter directed thrombolysis]], click [[Deep vein thrombosis invasive therapy|here]].'''''
 
===Indications===
* A Cochrane [[meta-analysis]] of [[randomized controlled trials]] showed reduced incidence of [[post-thrombotic syndrome]] and increased the vein patency, but it was associated with increased risk of bleeding.<ref name="pmid15495034">{{cite journal |author=Watson L, Armon M |title=Thrombolysis for acute deep vein thrombosis |journal=Cochrane Database Syst Rev|volume=|issue= |pages=CD002783 |year= |id=PMID 15495034}}</ref>
* [[Anticoagulation therapy]] is preferred over thrombolytic therapy in acute proximal DVT of the leg as well as in upper extremity DVT.
* According to ACCP guidelines, thrombolysis may be considered only in patients who meet all of the following criteria:<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest|volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref>
** Iliofemoral DVT
** Symptoms < 14 days
** Good functional status
** Life expectancy ≥1 year
** Low risk of bleeding
* Further, ACCP recommends using catheter-directed thrombolysis over systemic thrombolysis if resources and expertise is available.<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest|volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref>
 
=== Contraindications ===
Shown below is a table summarizing the absolute and relative contraindications to [[fibrinolytic therapy]] among [[pulmonary embolism]] patients.<ref name="pmid18757870">{{cite journal| author=Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P et al.| title=Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). | journal=Eur Heart J | year= 2008 | volume= 29 | issue= 18 | pages= 2276-315 | pmid=18757870 | doi=10.1093/eurheartj/ehn310 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18757870  }} </ref>
 
{| style="cellpadding=0; cellspacing= 0; width: 600px;"
|-
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[ACCP guidelines classification scheme#Grading Scheme Classification|Grade 1]]
| style="padding: 0 5px; font-size: 100%; background: #F5F5F5;" align="center" | '''Absolute contraindications'''|| style="padding: 0 5px; font-size: 100%; background: #F5F5F5;" align="center" | '''Relative contraindications'''
|-
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' In patients with acute DVT of the leg, we recommend early initiation of VKA (eg, same day as parenteral therapy is started) over delayed initiation, and continuation of parenteral anticoagulation for a minimum of 5 days and until the international normalized ratio (INR) is 2.0 or above for at least 24 h ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]])<nowiki>"</nowiki>
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align="left" |❑ Previous [[hemorrhagic stroke]] or [[stroke]] of unknown origin <br>
❑ [[Ischemic stroke]] within the last 6 months<br>
❑ [[Central nervous system]] tumor or damage <br>
❑ Major [[trauma]], head injury, or [[surgery]] within the last 3 weeks <br>
❑ [[Gastrointestinal bleed]] within the last month <br>
❑ Known [[bleeding]] <br>
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align="left" |❑ [[Transient ischemic attack]] within the last 6 months <br>
❑ [[Anticoagulation|Oral anticoagulant therapy]] intake <br>
❑ Advanced [[liver disease]] <br>
❑ [[Infective endocarditis]] <br>
❑ [[Peptic ulcer disease]] that is currently active <br>
❑ [[Pregnancy]] or within 1 week post partum <br>
❑ Punctures that are non-compressible <br>
❑ [[Resuscitation|Traumatic resuscitation]] <br>
❑ [[Systolic blood pressure]] >180 mmHg refractory to treatment
|}
 
==Compression Stockings==
* The daily use of knee-high elastic graduated compression stockings (EGCS) for 2 years following the diagnosis of first-episode of proximal DVT  is associated with marked reductions in the frequency of [[Post-thrombotic syndrome]] (PTS).<ref name="pmid15313740">{{cite journal| author=Prandoni P, Lensing AW, Prins MH, Frulla M, Marchiori A, Bernardi E et al.| title=Below-knee elastic compression stockings to prevent the post-thrombotic syndrome: a randomized, controlled trial. | journal=Ann Intern Med | year= 2004 | volume= 141 | issue= 4 | pages= 249-56 | pmid=15313740 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15313740  }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15656548 Review in: ACP J Club. 2005 Jan-Feb;142(1):7] </ref> <ref name="pmid15765034">{{cite journal| author=Partsch H, Kaulich M, Mayer W| title=Immediate mobilisation in acute vein thrombosis reduces post-thrombotic syndrome. | journal=Int Angiol | year= 2004 | volume= 23 | issue= 3 | pages= 206-12 | pmid=15765034 | doi= | pmc= | url= }} </ref>
 
* Elastic [[compression stockings]] should be routinely applied, beginning within 1 month of diagnosis of proximal DVT and continuing for a minimum of 1 year after diagnosis".<ref name="pmid15313740">{{cite journal| author=Prandoni P, Lensing AW, Prins MH, Frulla M, Marchiori A, Bernardi E et al.| title=Below-knee elastic compression stockings to prevent the post-thrombotic syndrome: a randomized, controlled trial. | journal=Ann Intern Med | year= 2004 | volume= 141 | issue= 4 | pages= 249-56 | pmid=15313740 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15313740  }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15656548 Review in: ACP J Club. 2005 Jan-Feb;142(1):7] </ref>  A cochrane [[meta-analysis]] of [[randomized controlled trials]] reported a reduced incidence of post-phlebitic syndrome with compression stockings use.<ref name="pmid14974060">{{cite journal |author=Kolbach D, Sandbrink M, Hamulyak K, Neumann H, Prins M |title=Non-pharmaceutical measures for prevention of post-thrombotic syndrome |journal=Cochrane Database Syst Rev |volume= |issue= |pages=CD004174 |year= |id=PMID 14974060 | doi = 10.1002/14651858.CD004174.pub2}}</ref> The [[number needed to treat]], that is, to prevent one case of [[post-thrombotic syndrome]] was 4.<ref name="pmid17003920">{{cite journal |author=Kakkos S, Daskalopoulou S, Daskalopoulos M, Nicolaides A, Geroulakos G |title=Review on the value of graduated elastic compression stockings after deep vein thrombosis |journal=Thromb Haemost |volume=96 |issue=4 |pages=441-5 |year=2006 |id=PMID 17003920}}</ref>
 
===Contraindicated Medications===
 
{{MedCondContrAbs
 
|MedCond = Deep vein thrombosis|Conjugated estrogens/bazedoxifene|Drospirenone and Ethinyl estradiol|Esterified estrogens|Medroxyprogesterone|Norgestrel and Ethinyl estradiol|Norelgestromin and Ethinyl Estradiol | Progesterone|Raloxifene}}
 
==2016 American College of Chest Physicians Evidence-Based Clinical Practice Guidelines on Antithrombotic Therapy for VTE Disease: Antithrombotic Therapy and Prevention of Thrombosis (DO NOT EDIT)<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest |volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref>==
 
===Initial Choice of Treatment in Patients with Acute DVT of the Leg (DO NOT EDIT)<ref name="pmid22315257">{{cite journal |author=Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ |title=Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=7S–47S |year=2012 |month=February |pmid=22315257 |doi=10.1378/chest.1412S3 |url=}}</ref>===
 
{| class="wikitable"
|-
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''2.''' In patients with acute DVT of the leg and whose home circumstances are adequate, we recommend initial treatment at home over treatment in hospital ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]).<nowiki>"</nowiki>
| colspan="1" style="text-align:center; background:LightGreen" |[[ACCP guidelines classification scheme#Grading Scheme Classification|Grade 1]]
|-
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''3.''' In patients with acute DVT of the leg who undergo thrombosis removal, we recommend the same intensity and duration of anticoagulant therapy as in comparable patients who do not undergo thrombosis removal ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]).<nowiki>"</nowiki>
| bgcolor="LightGreen" |<nowiki>"</nowiki>'''1.''' In patients with acute DVT of the leg, we recommend early initiation of VKA (eg, same day as parenteral therapy is started) over delayed initiation, and continuation of parenteral anticoagulation for a minimum of 5 days and until the international normalized ratio (INR) is 2.0 or above for at least 24 h (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]'')<nowiki>"</nowiki>
|-
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''4.''' In patients with acute DVT of the leg, we recommend against the use of an inferior vena cava (IVC) filter in addition to anticoagulants ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]).<nowiki>"</nowiki>
| bgcolor="LightGreen" |<nowiki>"</nowiki>'''2.''' In patients with acute DVT of the leg and whose home circumstances are adequate, we recommend initial treatment at home over treatment in hospital (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]'').<nowiki>"</nowiki>
|-
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''5.''' In patients with acute proximal DVT of the leg and contraindication to anticoagulation, we recommend the use of an IVC filter ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]).<nowiki>"</nowiki>
| bgcolor="LightGreen" |<nowiki>"</nowiki>'''3.''' In patients with acute DVT of the leg who undergo thrombosis removal, we recommend the same intensity and duration of anticoagulant therapy as in comparable patients who do not undergo thrombosis removal (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]'').<nowiki>"</nowiki>
|-
| bgcolor="LightGreen" |<nowiki>"</nowiki>'''4.''' In patients with acute DVT of the leg, we recommend against the use of an inferior vena cava (IVC) filter in addition to anticoagulants (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]'').<nowiki>"</nowiki>
|-
| bgcolor="LightGreen" |<nowiki>"</nowiki>'''5.''' In patients with acute proximal DVT of the leg and contraindication to anticoagulation, we recommend the use of an IVC filter (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]'').<nowiki>"</nowiki>
|}
|}


{|class="wikitable"
{| class="wikitable"
|-
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACCP guidelines classification scheme#Grading Scheme Classification|Grade 2]]
| colspan="1" style="text-align:center; background:LemonChiffon" |[[ACCP guidelines classification scheme#Grading Scheme Classification|Grade 2]]
|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' In patients with acute DVT of the leg, we suggest LMWH or fondaparinux over IV UFH ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence C]]) and over SC UFH ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]) for LMWH;([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence C]]) for fondaparinux).<nowiki>"</nowiki>
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''1.''' In patients with acute DVT of the leg, we suggest LMWH or fondaparinux over IV UFH (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence C]]'') and over SC UFH (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]'') for LMWH;(''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence C]]'') for fondaparinux).<nowiki>"</nowiki>
|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''2.''' In patients with acute DVT of the leg treated with LMWH, we suggest once- over twice-daily administration ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence C]]).<nowiki>"</nowiki>
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''2.''' In patients with acute DVT of the leg treated with LMWH, we suggest once- over twice-daily administration (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence C]]'').<nowiki>"</nowiki>
|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''3.''' In patients with acute proximal DVT of the leg, we suggest anti coagulant therapy alone over catheter-directed thrombolysis (CDT) ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence C]]).<nowiki>"</nowiki>
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''3.''' In patients with acute proximal DVT of the leg, we suggest anti coagulant therapy alone over catheter-directed thrombolysis (CDT) (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence C]]'').<nowiki>"</nowiki>
|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''4.''' In patients with acute proximal DVT of the leg, we suggest anticoagulant therapy alone over systemic thrombolysis ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence C]]).<nowiki>"</nowiki>
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''4.''' In patients with acute proximal DVT of the leg, we suggest anticoagulant therapy alone over systemic thrombolysis (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence C]]'').<nowiki>"</nowiki>
|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''5.''' In patients with acute proximal DVT of the leg, we suggest anticoagulant therapy alone over operative venous thrombectomy ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence C]]).<nowiki>"</nowiki>
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''5.''' In patients with acute proximal DVT of the leg, we suggest anticoagulant therapy alone over operative venous thrombectomy (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence C]]'').<nowiki>"</nowiki>
|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''6.''' In patients with acute proximal DVT of the leg and an IVC filter inserted as an alternative to anticoagulation, we suggest a conventional course of anticoagulant therapy if their risk of bleeding resolves ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]).<nowiki>"</nowiki>
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''6.''' In patients with acute proximal DVT of the leg and an IVC filter inserted as an alternative to anticoagulation, we suggest a conventional course of anticoagulant therapy if their risk of bleeding resolves (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]'').<nowiki>"</nowiki>
|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''7.''' In patients with acute DVT of the leg, we suggest early ambulation over initial bed rest ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence C]]).<nowiki>"</nowiki>
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''7.''' In patients with acute DVT of the leg, we suggest early ambulation over initial bed rest (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence C]]'').<nowiki>"</nowiki>
|}
|}
==ACCP Guidelines: Recommendations for duration of anticoagulant therapy (DO NOT EDIT)==
<ref name="pmid22315257">{{cite journal |author=Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ |title=Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=7S–47S |year=2012 |month=February |pmid=22315257 |doi=10.1378/chest.1412S3 |url=}}</ref>


{|class="wikitable"
===Duration of Anticoagulant Therapy (DO NOT EDIT)<ref name="pmid22315257">{{cite journal |author=Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ |title=Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=7S–47S |year=2012 |month=February |pmid=22315257 |doi=10.1378/chest.1412S3 |url=}}</ref>===
 
{| class="wikitable"
|-
| colspan="1" style="text-align:center; background:LightGreen" |[[ACCP guidelines classification scheme#Grading Scheme Classification|Grade 1]]
|-
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[ACCP guidelines classification scheme#Grading Scheme Classification|Grade 1]]
| bgcolor="LightGreen" | <nowiki>"</nowiki>'''1.''' In patients with acute VTE who are treated with anticoagulant therapy, we recommend long-term therapy over stopping anticoagulant therapy after about 1 week of initial therapy (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]'')<nowiki>"</nowiki>
|-
|-
| bgcolor="LightGreen"| <nowiki>"</nowiki>'''1.''' In patients with acute VTE who are treated with anticoagulant therapy, we recommend long-term therapy (see section 3.1 for recommended duration of therapy) over stopping anticoagulant therapy after about 1 week of initial therapy ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]])<nowiki>"</nowiki>
| bgcolor="LightGreen" | <nowiki>"</nowiki>'''2.''' In patients with a proximal DVT of the leg provoked by surgery, we recommend treatment with anticoagulation for 3 months over (i) treatment of a shorter period (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]'')<nowiki>"</nowiki> , (ii) treatment of a longer time-limited period (eg, 6 or 12 months) (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]'') , or (iii) extended therapy (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]'' regardless of bleeding risk).<nowiki>"</nowiki>
|-
|-
| bgcolor="LightGreen"| <nowiki>"</nowiki>'''2.''' In patients with a proximal DVT of the leg provoked by surgery, we recommend treatment with anticoagulation for 3 months over (i) treatment of a shorter period ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]])<nowiki>"</nowiki> , (ii) treatment of a longer time-limited period (eg, 6 or 12 months) ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]) , or (iii) extended therapy ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]] regardless of bleeding risk).<nowiki>"</nowiki>
| bgcolor="LightGreen" | <nowiki>"</nowiki>'''3.''' In patients with a proximal DVT of the leg provoked by a nonsurgical transient risk factor, we recommend treatment with anticoagulation for 3 months over (i) treatment of a shorter period (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]'') , (ii) treatment of a longer time-limited period (eg, 6 or 12 months) (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]''), and (iii) extended therapy if there is a high bleeding risk (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]'') .<nowiki>"</nowiki>  
|-
|-
| bgcolor="LightGreen"| <nowiki>"</nowiki>'''3.''' In patients with a proximal DVT of the leg provoked by a nonsurgical transient risk factor, we recommend treatment with anticoagulation for 3 months over (i) treatment of a shorter period ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]) , (ii) treatment of a longer time-limited period (eg, 6 or 12 months) ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]), and (iii) extended therapy if there is a high bleeding risk ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]) .<nowiki>"</nowiki>  
| bgcolor="LightGreen" |<nowiki>"</nowiki>'''4.''' In patients with an isolated distal DVT of the leg provoked by surgery or by a nonsurgical transient risk factor , we recommend treatment with anticoagulation for 3 months over treatment of a longer time-limited period (eg, 6 or 12 months) (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]'') or extended therapy (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]'') regardless of bleeding risk. <nowiki>"</nowiki>
|-
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''4.''' In patients with an isolated distal DVT of the leg provoked by surgery or by a nonsurgical transient risk factor , we recommend treatment with anticoagulation for 3 months over treatment of a longer time-limited period (eg, 6 or 12 months) ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]) or extended therapy ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]) regardless of bleeding risk. <nowiki>"</nowiki>
| bgcolor="LightGreen" | <nowiki>"</nowiki>'''5.''' In patients with an unprovoked DVT of the leg (isolated distal or proximal), we recommend treatment with anticoagulation for at least 3 months over treatment of a shorter duration (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]'') . After 3 months of treatment, patients with unprovoked DVT of the leg should be evaluated for the risk-benefit ratio of extended therapy. <nowiki>"</nowiki>
|-
|-
| bgcolor="LightGreen"| <nowiki>"</nowiki>'''5.''' In patients with an unprovoked DVT of the leg (isolated distal [see remark] or proximal), we recommend treatment with anticoagulation for at least 3 months over treatment of a shorter duration ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]) . After 3 months of treatment, patients with unprovoked DVT of the leg should be evaluated for the risk-benefit ratio of extended therapy. <nowiki>"</nowiki>
| bgcolor="LightGreen" | <nowiki>"</nowiki>'''6.''' Anticoagulation should be given for 3 months in patients with a first unprovoked VTE and a high risk of bleeding (''[[ACCP guidelines classification scheme|Level of Evidence B]]''), but should be extended without a scheduled stop date in patients with a low or moderate risk of bleeding (''[[ACCP guidelines classification scheme|Level of Evidence B]]'').
|-
|-
| bgcolor="LightGreen"| <nowiki>"</nowiki>'''6.''' In patients with a first VTE that is an unprovoked proximal DVT of the leg and who have a high bleeding risk, we recommend 3 months of anticoagulant therapy over extended therapy ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]). <nowiki>"</nowiki>
| bgcolor="LightGreen" | <nowiki>"</nowiki>'''7.''' In patients with a first VTE that is an unprovoked proximal DVT of the leg and who have a high bleeding risk, we recommend 3 months of anticoagulant therapy over extended therapy (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]''). <nowiki>"</nowiki>
|-
|-
| bgcolor="LightGreen"| <nowiki>"</nowiki>'''7.''' In patients with a first VTE that is an unprovoked isolated distal DVT of the leg, we recommend 3 months of anticoagulant treatment in those with a high bleeding risk ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]).<nowiki>"</nowiki>
| bgcolor="LightGreen" | <nowiki>"</nowiki>'''8.''' In patients with a first VTE that is an unprovoked isolated distal DVT of the leg, we recommend 3 months of anticoagulant treatment in those with a high bleeding risk (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]'').<nowiki>"</nowiki>
|-
|-
| bgcolor="LightGreen"| <nowiki>"</nowiki>'''8.''' In patients with a second unprovoked VTE, we recommend extended anticoagulant therapy over 3 months of therapy in those who have a low bleeding risk ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]])<nowiki>"</nowiki>.
| bgcolor="LightGreen" | <nowiki>"</nowiki>'''9.''' In patients with a second unprovoked VTE, we recommend extended anticoagulant therapy over 3 months of therapy in those who have a low bleeding risk (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]'')<nowiki>"</nowiki>.
|-
|-
| bgcolor="LightGreen"| <nowiki>"</nowiki>'''9.''' In all patients who receive extended anticoagulant therapy, the continuing use of treatment should be reassessed at periodic intervals (eg, annually).<nowiki>"</nowiki>
| bgcolor="LightGreen" | <nowiki>"</nowiki>'''10.''' In all patients who receive extended anticoagulant therapy, the continuing use of treatment should be reassessed at periodic intervals (eg, annually).<nowiki>"</nowiki>
|-
|-
| bgcolor="LightGreen"| <nowiki>"</nowiki>'''10.''' In patients with DVT of the leg and active cancer, if the risk of bleeding is not high, we recommend extended anticoagulant therapy over 3 months of therapy ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]])<nowiki>"</nowiki>.
| bgcolor="LightGreen" | <nowiki>"</nowiki>'''11.''' In patients with DVT of the leg and active cancer, if the risk of bleeding is not high, we recommend extended anticoagulant therapy over 3 months of therapy (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]'')<nowiki>"</nowiki>.
|}
|}


{|class="wikitable"
{| class="wikitable"
|-
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACCP guidelines classification scheme#Grading Scheme Classification|Grade 2]]
| colspan="1" style="text-align:center; background:LemonChiffon" |[[ACCP guidelines classification scheme#Grading Scheme Classification|Grade 2]]
|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' In patients with DVT of the leg and active cancer, if there is a high bleeding risk, we suggest extended anticoagulant therapy ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]).<nowiki>"</nowiki>
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''1.''' In patients with DVT of the leg and active cancer, if there is a high bleeding risk, we suggest extended anticoagulant therapy (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]'').<nowiki>"</nowiki>
|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''2.''' In patients with a first VTE that is an unprovoked proximal DVT of the leg and who have a low or moderate bleeding risk, we suggest extended anticoagulant therapy over 3 months of therapy ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]).<nowiki>"</nowiki>
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''2.''' In patients with a first VTE that is an unprovoked proximal DVT of the leg and who have a low or moderate bleeding risk, we suggest extended anticoagulant therapy over 3 months of therapy (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]'').<nowiki>"</nowiki>
|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''3.''' In patients with a second unprovoked VTE who have a high bleeding risk, we suggest 3 months of anticoagulant therapy over extended therapy ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]).<nowiki>"</nowiki>
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''3.''' In patients with a second unprovoked VTE who have a high bleeding risk, we suggest 3 months of anticoagulant therapy over extended therapy (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]'').<nowiki>"</nowiki>


|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>4. In patients with a proximal DVT of the leg provoked by a nonsurgical transient risk factor,We suggest treatment with anticoagulation for 3 months over extended therapy if there is a low or moderate bleeding risk ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]).<nowiki>"</nowiki>
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''4.''' In patients with a proximal DVT of the leg provoked by a nonsurgical transient risk factor,We suggest treatment with anticoagulation for 3 months over extended therapy if there is a low or moderate bleeding risk (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]'').<nowiki>"</nowiki>


|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>5.In patients with an isolated distal DVT of the leg provoked by surgery or by a nonsurgical transient risk factor , we suggest treatment with anticoagulation for 3 months over treatment of a shorter period ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence C]]). <nowiki>"</nowiki>
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''5.'''In patients with an isolated distal DVT of the leg provoked by surgery or by a nonsurgical transient risk factor , we suggest treatment with anticoagulation for 3 months over treatment of a shorter period (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence C]]''). <nowiki>"</nowiki>


|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>6. In patients with a first VTE that is an unprovoked isolated distal DVT of the leg, we suggest 3 months of anticoagulant therapy over extended therapy in those with a low or moderate bleeding risk ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]).<nowiki>"</nowiki>
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''6.''' In patients with a first VTE that is an unprovoked isolated distal DVT of the leg, we suggest 3 months of anticoagulant therapy over extended therapy in those with a low or moderate bleeding risk (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]'').<nowiki>"</nowiki>


|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>7. In patients with a second unprovoked VTE, we suggest extended anticoagulant therapy in those with a moderate bleeding risk ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]). <nowiki>"</nowiki>
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''7.''' In patients with a second unprovoked VTE, we suggest extended anticoagulant therapy in those with a moderate bleeding risk (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]''). <nowiki>"</nowiki>


|}
|}


==AHA Guidelines for duration of anticoagulant therapy==
===Duration of Anticoagulant Therapy (DO NOT EDIT)<ref name="pmid21422387">{{cite journal |author=Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ, Jenkins JS, Kline JA, Michaels AD, Thistlethwaite P, Vedantham S, White RJ, Zierler BK |title=Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association |journal=Circulation |volume=123 |issue=16|pages=1788–830 |year=2011 |month=April |pmid=21422387 |doi=10.1161/CIR.0b013e318214914f |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=21422387 |accessdate=2012-02-11}}</ref>===
<ref name="pmid21422387">{{cite journal |author=Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ, Jenkins JS, Kline JA, Michaels AD, Thistlethwaite P, Vedantham S, White RJ, Zierler BK |title=Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association |journal=Circulation |volume=123 |issue=16|pages=1788–830 |year=2011 |month=April |pmid=21422387 |doi=10.1161/CIR.0b013e318214914f |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=21422387 |accessdate=2012-02-11}}</ref>


'''1.''' Adult patients with IFDVT who receive oral warfarin as first-line long-term anticoagulation therapy should have warfarin overlapped with initial anticoagulation therapy for a minimum of 5 days and until the INR is ≥2.0 for at least 24 hours, and then targeted to an INR of 2.0 to 3.0 ([[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]; Level of Evidence A).  
{| class="wikitable"
|-
| colspan="1" style="text-align:center; background:LightGreen" |[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
|-
| bgcolor="LightGreen" |<nowiki>"</nowiki>'''1.''' Adult patients with IFDVT who receive oral warfarin as first-line long-term anticoagulation therapy should have warfarin overlapped with initial anticoagulation therapy for a minimum of 5 days and until the INR is ≥2.0 for at least 24 hours, and then targeted to an INR of 2.0 to 3.0 (''[[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]]'') <nowiki>"</nowiki>
|-
| bgcolor="LightGreen" |<nowiki>"</nowiki>'''2.''' Patients with first-episode IFDVT related to a major reversible risk factor should have anticoagulation stopped after 3 months  (''[[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]]'').<nowiki>"</nowiki>
|-
| bgcolor="LightGreen" |<nowiki>"</nowiki>'''3.''' Patients with recurrent or unprovoked IFDVT should have at least 6 months of anticoagulation and be considered for indefinite anticoagulation with periodic reassessment of the risks and benefits of continued anticoagulation (''[[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]]'').<nowiki>"</nowiki>
|-
| bgcolor="LightGreen" |<nowiki>"</nowiki>'''4.'''  Cancer patients with IFDVT should receive LMWH monotherapy for at least 3 to 6 months, or as long as the cancer or its treatment (eg, chemotherapy) is ongoing  (''[[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]]'').  <nowiki>"</nowiki>
|}
{| class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon" | [[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIb]]
|-
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''1.'''  In children with DVT, the use of LMWH monotherapy may be reasonable (''[[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]]''). <nowiki>"</nowiki>
|}


'''2.''' Patients with first-episode IFDVT related to a major reversible risk factor should have anticoagulation stopped after 3 months  ([[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]; Level of Evidence A).
===Intensity of Anticoagulant Effect (DO NOT EDIT)<ref name="pmid22315257">{{cite journal |author=Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ |title=Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=7S–47S |year=2012 |month=February |pmid=22315257 |doi=10.1378/chest.1412S3 |url=}}</ref>===


'''3.''' Patients with recurrent or unprovoked IFDVT should have at least 6 months of anticoagulation and be considered for indefinite anticoagulation with periodic reassessment of the risks and benefits of continued anticoagulation ([[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]; Level of Evidence A).
{| class="wikitable"
 
'''4.'''  Cancer patients with IFDVT should receive LMWH monotherapy for at least 3 to 6 months, or as long as the cancer or its treatment (eg, chemotherapy) is ongoing  ([[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]; Level of Evidence A). 
 
'''5.'''  In children with DVT, the use of LMWH monotherapy may be reasonable ([[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIb]]; Level of Evidence C).
 
==ACCP Guidelines: Recommendations for intensity of anticoagulant effect (DO NOT EDIT)==
 
<ref name="pmid22315257">{{cite journal |author=Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ |title=Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=7S–47S |year=2012 |month=February |pmid=22315257 |doi=10.1378/chest.1412S3 |url=}}</ref>
 
{|class="wikitable"
|-
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[ACCP guidelines classification scheme#Grading Scheme Classification|Grade 1]]
| colspan="1" style="text-align:center; background:LightGreen" |[[ACCP guidelines classification scheme#Grading Scheme Classification|Grade 1]]
|-
|-
| bgcolor="LightGreen"| <nowiki>"</nowiki>'''1.'''In patients with DVT of the leg who are treated with VKA, we recommend a therapeutic INR range of 2.0 to 3.0 (target INR of 2.5) over a lower (INR <2) or higher (INR 3.0-5.0) range for all treatment durations ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]])<nowiki>"</nowiki>.
| bgcolor="LightGreen" | <nowiki>"</nowiki>'''1.'''In patients with DVT of the leg who are treated with VKA, we recommend a therapeutic INR range of 2.0 to 3.0 (target INR of 2.5) over a lower (INR <2) or higher (INR 3.0-5.0) range for all treatment durations (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]'')<nowiki>"</nowiki>.
|}
|}


==ACCP Guidelines: Recommendations for treatment of isolated distal DVT (DO NOT EDIT)==
===Treatment of Isolated Distal DVT (DO NOT EDIT)<ref name="pmid22315257">{{cite journal |author=Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ |title=Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=7S–47S |year=2012 |month=February |pmid=22315257 |doi=10.1378/chest.1412S3 |url=}}</ref>===


<ref name="pmid22315257">{{cite journal |author=Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ |title=Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=7S–47S |year=2012 |month=February |pmid=22315257 |doi=10.1378/chest.1412S3 |url=}}</ref>
{| class="wikitable"
 
{|class="wikitable"
|-
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[ACCP guidelines classification scheme#Grading Scheme Classification|Grade 1]]
| colspan="1" style="text-align:center; background:LightGreen" |[[ACCP guidelines classification scheme#Grading Scheme Classification|Grade 1]]
|-
|-
| bgcolor="LightGreen"| <nowiki>"</nowiki>'''1.''' In patients with acute isolated distal DVT of the leg who are managed with initial anticoagulation, we recommend using the same approach as for patients with acute proximal DVT ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]). <nowiki>"</nowiki>
| bgcolor="LightGreen" | <nowiki>"</nowiki>'''1.''' In patients with acute isolated distal DVT of the leg who are managed with initial anticoagulation, we recommend using the same approach as for patients with acute proximal DVT (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]''). <nowiki>"</nowiki>


|-
|-
| bgcolor="LightGreen"| <nowiki>"</nowiki>'''2.''' In patients with acute isolated distal DVT of the leg who are managed with serial imaging, we recommend no anticoagulation if the thrombus does not extend ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]) ; we recommend anticoagulation if the thrombus extends into the proximal veins ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]). <nowiki>"</nowiki>
| bgcolor="LightGreen" | <nowiki>"</nowiki>'''2.''' In patients with acute isolated distal DVT of the leg who are managed with serial imaging, we recommend no anticoagulation if the thrombus does not extend (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]'') ; we recommend anticoagulation if the thrombus extends into the proximal veins (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]''). <nowiki>"</nowiki>
|}
|}
{|class="wikitable"
{| class="wikitable"
|-
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACCP guidelines classification scheme#Grading Scheme Classification|Grade 2]]
| colspan="1" style="text-align:center; background:LemonChiffon" |[[ACCP guidelines classification scheme#Grading Scheme Classification|Grade 2]]
|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' In patients with acute isolated distal DVT of the leg and without severe symptoms or risk factors for extension, we suggest serial imaging of the deep veins for 2 weeks over initial anticoagulation ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence C]]).<nowiki>"</nowiki>
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''1.''' In patients with acute isolated distal DVT of the leg and without severe symptoms or risk factors for extension, we suggest serial imaging of the deep veins for 2 weeks over initial anticoagulation (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence C]]'').<nowiki>"</nowiki>


|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''2.''' In patients with acute isolated distal DVT of the leg and severe symptoms or risk factors for extension (see text), we suggest initial anticoagulation over serial imaging of the deep veins ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence C]]).<nowiki>"</nowiki>
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''2.''' In patients with acute isolated distal DVT of the leg and severe symptoms or risk factors for extension (see text), we suggest initial anticoagulation over serial imaging of the deep veins (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence C]]'').<nowiki>"</nowiki>


|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''3.''' In patients with acute isolated distal DVT of the leg who are managed with serial imaging, we suggest anticoagulation if the thrombus extends but remains confined to the distal veins ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence C]]).<nowiki>"</nowiki>
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''3.''' In patients with acute isolated distal DVT of the leg who are managed with serial imaging, we suggest anticoagulation if the thrombus extends but remains confined to the distal veins (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence C]]'').<nowiki>"</nowiki>


|}
|}


==ACCP Guidelines: Recommendations for treatment of asymptomatic DVT of the leg (DO NOT EDIT)==
===Treatment of Asymptomatic DVT of the Leg (DO NOT EDIT)<ref name="pmid22315257">{{cite journal |author=Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ |title=Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=7S–47S |year=2012 |month=February |pmid=22315257 |doi=10.1378/chest.1412S3 |url=}}</ref>===
{|class="wikitable"
{| class="wikitable"
|-
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACCP guidelines classification scheme#Grading Scheme Classification|Grade 2]]
| colspan="1" style="text-align:center; background:LemonChiffon" |[[ACCP guidelines classification scheme#Grading Scheme Classification|Grade 2]]
|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' In patients who are incidentally found to have asymptomatic DVT of the leg, we suggest the same initial and long-term anticoagulation as for comparable patients with symptomatic DVT ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]])<nowiki>"</nowiki>.
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''1.''' In patients who are incidentally found to have asymptomatic DVT of the leg, we suggest the same initial and long-term anticoagulation as for comparable patients with symptomatic DVT (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]'')<nowiki>"</nowiki>.
|}
|}


==ACCP Guidelines: Recommendations for treatment in special situations (DO NOT EDIT)==
===Treatment of Acute Upper Extremity DVT (DO NOT EDIT)<ref name="pmid22315257">{{cite journal |author=Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ |title=Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=7S–47S |year=2012 |month=February |pmid=22315257 |doi=10.1378/chest.1412S3 |url=}}</ref>===
<ref name="pmid22315257">{{cite journal |author=Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ |title=Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=7S–47S |year=2012 |month=February |pmid=22315257 |doi=10.1378/chest.1412S3 |url=}}</ref>


{|class="wikitable"
{| class="wikitable"
|-
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACCP guidelines classification scheme#Grading Scheme Classification|Grade 2]]
| colspan="1" style="text-align:center; background:LightGreen" |[[ACCP guidelines classification scheme#Grading Scheme Classification|Grade 1]]
|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' In patients with DVT of the leg and no cancer, we suggest VKA therapy over LMWH for long-term therapy ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence C]]) . For patients with DVT and no cancer who are not treated with VKA therapy, we suggest LMWH over dabigatran or rivaroxaban for long-term therapy ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence C]])<nowiki>"</nowiki>.
| bgcolor="LightGreen" |<nowiki>"</nowiki>'''1.''' In patients with UEDVT who undergo thrombolysis, we recommend the same intensity and duration of anticoagulant therapy as in similar patients who do not undergo thrombolysis. (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]'') <nowiki>"</nowiki>
|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''2.''' In patients with DVT of the leg and cancer, we suggest LMWH over VKA therapy ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]). In patients with DVT and cancer who are not treated with LMWH, we suggest VKA over dabigatran or rivaroxaban for long-term therapy ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]).
|}
 
{| class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon" |[[ACCP guidelines classification scheme#Grading Scheme Classification|Grade 2]]
|-
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''1.''' In patients with acute UEDVT that involves the axillary or more proximal veins, we suggest anticoagulant therapy alone over thrombolysis. (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence C]]'') <nowiki>"</nowiki>.
|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''3.''' In patients with DVT of the leg who receive extended therapy, we suggest treatment with the same anticoagulant chosen for the first 3 months ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence C]]).
|}
|}


==ACCP Guidelines: Recommendations for post-thrombotic syndrome (DO NOT EDIT)==
===Treatment in Special Situations (DO NOT EDIT)<ref name="pmid22315257">{{cite journal |author=Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ |title=Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=7S–47S |year=2012 |month=February |pmid=22315257 |doi=10.1378/chest.1412S3 |url=}}</ref>===
<ref name="pmid22315257">{{cite journal |author=Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ |title=Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=7S–47S |year=2012 |month=February |pmid=22315257 |doi=10.1378/chest.1412S3 |url=}}</ref>


{|class="wikitable"
{| class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACCP guidelines classification scheme#Grading Scheme Classification|Grade 2]]
|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' In patients with acute symptomatic DVT of the leg, we suggest the use of compression stockings ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]). <nowiki>"</nowiki>
| colspan="1" style="text-align:center; background:LemonChiffon" |[[ACCP guidelines classification scheme#Grading Scheme Classification|Grade 2]]
|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''2.''' In patients with PTS of the leg, we suggest a trial of compression stockings ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence C]]). <nowiki>"</nowiki>
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''1.''' In patients with VTE without an associated cancer diagnosis, all direct oral anticoagulants (dabigatran, rivaroxaban, apixaban, or edoxaban) are recommended over vitamin K antagonist (VKA) therapy ([[ACCP guidelines classification scheme|Level of Evidence: B]]) and VKA therapy is recommended over low molecular weight heparin (LMWH; ''[[ACCP guidelines classification scheme|Level of Evidence: C]]'').
|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''3.''' In patients with severe PTS of the leg that is not adequately relieved by compression stockings, we suggest a trial of an intermittent compression  device ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]). <nowiki>"</nowiki>
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''2.''' In patients with DVT of the leg and cancer, we suggest LMWH over VKA therapy (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]''). In patients with DVT and cancer who are not treated with LMWH, we suggest VKA over dabigatran or rivaroxaban for long-term therapy (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]'').
|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''4.''' In patients with PTS of the leg, we suggest that venoactive medications (eg, rutosides, defibrotide, and hidrosmin) not be used ([[ACCP guidelines classification scheme#Level of Evidence|Level of evidence C]]). <nowiki>"</nowiki>
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''3.''' In patients with DVT of the leg who receive extended therapy, we suggest treatment with the same anticoagulant chosen for the first 3 months (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence C]]'').
|}
|}


== Iliofemoral DVT (IFDVT)==
===Post-Thrombotic Syndrome (DO NOT EDIT)<ref name="pmid22315257">{{cite journal |author=Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ |title=Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=7S–47S |year=2012 |month=February |pmid=22315257 |doi=10.1378/chest.1412S3 |url=}}</ref>===
Iliofemoral DVT (IFDVT) mainly affects the complete or (partial thrombosis of) any part of the [[iliac vein]] or the common [[femoral vein]], with or without involvement of other lower extremity veins or the [[Inferior vena cava]]. The clot can block blood flow and cause swelling and pain.  There is a significant risk involved, when a thrombus embolizes and travels to the lungs, causing [[pulmonary embolism]].


===ACC/AHA Guidelines- Recommendations for Initial Anticoagulation for Patients With IFDVT (DO NOT EDIT)===
{| class="wikitable"
<ref name="pmid21422387">{{cite journal| author=Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ et al.| title=Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. | journal=Circulation | year= 2011 | volume= 123 | issue= 16 | pages= 1788-830 | pmid=21422387 | doi=10.1161/CIR.0b013e318214914f | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21422387  }} </ref>
{|class="wikitable"
|-
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
| colspan="1" style="text-align:center; background:LemonChiffon" |[[ACCP guidelines classification scheme#Grading Scheme Classification|Grade 2]]
|-
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' In the absence of suspected or proven [[Heparin-induced thrombocytopenia|heparin-induced thrombocytopenia]], patients with IFDVT should receive therapeutic anticoagulation with either intravenous [[UFH]] ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])'', UFH by subcutaneous injection ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'', an LMWH ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])'', or fondaparinux ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])''.<nowiki>"</nowiki>
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''1.''' In patients with acute DVT, the guideline recommends against the use of compression stockings routinely to prevent the post-thrombotic syndrome (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]''). <nowiki>"</nowiki>
 
|-
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''2.''' In patients with PTS of the leg, we suggest a trial of compression stockings (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence C]]''). <nowiki>"</nowiki>
|-
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''3.''' In patients with severe PTS of the leg that is not adequately relieved by compression stockings, we suggest a trial of an intermittent compression  device (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]''). <nowiki>"</nowiki>
|-
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''2.''' Patients with IFDVT who have suspected or proven [[Heparin-induced thrombocytopenia|heparin-induced thrombocytopenia]] should receive a [[Direct thrombin inhibitor|direct thrombin inhibitor]] ([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''4.''' In patients with PTS of the leg, we suggest that venoactive medications (eg, rutosides, defibrotide, and hidrosmin) not be used (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence C]]''). <nowiki>"</nowiki>
 
|}
|}


===ACC/AHA Guidelines- Recommendations for Long-Term Anticoagulation Therapy for Patients With IFDVT (DO NOT EDIT)===
===Subsegmental PE Without DVT===
<ref name="pmid21422387">{{cite journal| author=Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ et al.| title=Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. | journal=Circulation | year= 2011 | volume= 123 | issue= 16 | pages= 1788-830 | pmid=21422387 | doi=10.1161/CIR.0b013e318214914f | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21422387  }} </ref>
{| class="wikitable"
 
{|class="wikitable"
|-
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
| colspan="1" style="text-align:center; background:LemonChiffon" |[[ACCP guidelines classification scheme#Grading Scheme Classification|Grade 2]]
|-
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' Adult patients with IFDVT who receive oral warfarin as first-line long-term anticoagulation therapy should have warfarin overlapped with initial anticoagulation therapy for a minimum of 5 days and until the INR is ≥2.0 for at least 24 hours, and then targeted to an INR of 2.0 to 3.0 ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])''.<nowiki>"</nowiki>
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''1.''For patient with subsegmental PE and no DVT, the guideline suggests clinical surveillance over anticoagulation when the risk of VTE recurrence is low (''[[ACCP guidelines classification scheme|Level of Evidence C]]''). The guideline recommends the use of anticoagulation over surveillance when the risk of VTE recurrence is high (''[[ACCP guidelines classification scheme|Level of Evidence C]]''). <nowiki>"</nowiki>
|}


===Prevention of Recurrent VTE after unprovoked Proximal DVT or PE===
{| class="wikitable"
|-
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''2.''' Patients with first-episode IFDVT related to a major reversible risk factor should have anticoagulation stopped after 3 months ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])''<nowiki>"</nowiki>
| colspan="1" style="text-align:center; background:LemonChiffon" |[[ACCP guidelines classification scheme#Grading Scheme Classification|Grade 2]]
 
|-
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''3.''' Patients with recurrent or unprovoked IFDVT should have at least 6 months of anticoagulation and be considered for indefinite anticoagulation with periodic reassessment of the risks and benefits of continued anticoagulation ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])''<nowiki>"</nowiki>
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''1.'''For patients with an unprovoked proximal DVT or PE who are stopping anticoagulant therapy, the guideline suggests the use of aspirin over no aspirin to prevent recurrent VTE if there are no contraindications to aspirin therapy  (''[[ACCP guidelines classification scheme#Level of Evidence|Level of evidence B]]''). <nowiki>"</nowiki>
 
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''4.''' Cancer patients with IFDVT should receive LMWH monotherapy for at least 3 to 6 months, or as long as the cancer or its treatment (eg, chemotherapy) is ongoing ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])''<nowiki>"</nowiki>
|}
|}


{|class="wikitable"
=== Recurrent VTE while on Non-LMWH Anticoagulant ===
{| class="wikitable"
|-
|-
| colspan="1" style="text-align:center; background:LemonChiffon"| [[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIa]]
| colspan="1" style="text-align:center; background:LemonChiffon" |[[ACCP guidelines classification scheme#Grading Scheme Classification|Grade 2]]
|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' In children with DVT, the use of LMWH monotherapy may be reasonable ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''1.''For patients with recurrent VTE while treated with a non-LMWH anticoagulant, the guideline recommends changing to LMWH therapy (Level of Evidence C). If patients suffer a recurrent VTE while on LMWH treatment, the guideline recommends increasing the LMWH dose (Level of Evidence C). <nowiki>"</nowiki>
|}


|}
==2011 AHA Scientific Statement- Management of Massive and Submassive Pulmonary Embolism, Iliofemoral Deep Vein Thrombosis, and Chronic Thromboembolic Pulmonary Hypertension (DO NOT EDIT)<ref name="pmid21422387">{{cite journal| author=Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ et al.| title=Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. | journal=Circulation | year= 2011 | volume= 123 | issue= 16 | pages= 1788-830 | pmid=21422387 | doi=10.1161/CIR.0b013e318214914f | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21422387  }} </ref>==


==Thrombolysis==
===Anticoagulation for Patients With IFDVT (DO NOT EDIT)<ref name="pmid21422387">{{cite journal| author=Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ et al.| title=Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. | journal=Circulation | year= 2011 | volume= 123 | issue= 16 | pages= 1788-830 | pmid=21422387 | doi=10.1161/CIR.0b013e318214914f | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21422387  }} </ref>===
===Catheter-Directed Thrombolysis===
* Catheter-Directed Thrombolysis for acute [[DVT]] has been evaluated in small randomized trials and have shown that it may preserve venous valve function, reduce [[post-thrombotic syndrome]] and improve quality of life. However, evidence regarding mortality, recurrent [[VTE]] and major bleeding is lacking.
* According to ACCP guidelines<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref>, catheter-directed thrombolysis should be considered only in patients who meet all of the following criteria:
** Iliofemoral [[DVT]]
** Symptoms < 14 days
** Good functional status
** Life expectancy ≥1 year
** Low risk of bleeding


'''ACCP recommendations<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref>:'''
{| class="wikitable"
{{cquote|
|-
'''1.''' In patients with acute proximal DVT of the leg, we suggest anticoagulant therapy alone over CDT (Grade 2C).
| colspan="1" style="text-align:center; background:LightGreen" |[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
|-
| bgcolor="LightGreen" |<nowiki>"</nowiki>'''1.''' In the absence of suspected or proven [[Heparin-induced thrombocytopenia|heparin-induced thrombocytopenia]], patients with IFDVT should receive therapeutic anticoagulation with either intravenous [[UFH]] ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])'', UFH by subcutaneous injection ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'', an LMWH ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])'', or fondaparinux ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])''.<nowiki>"</nowiki>


'''2.''' In patients with acute DVT of the leg who undergo thrombosis removal, we recommend the same intensity and duration of anticoagulant therapy as in similar patients who do not undergo thrombosis removal.}}
|-
| bgcolor="LightGreen" |<nowiki>"</nowiki>'''2.''' Patients with IFDVT who have suspected or proven [[Heparin-induced thrombocytopenia|heparin-induced thrombocytopenia]] should receive a [[Direct thrombin inhibitor|direct thrombin inhibitor]] (''[[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]]'')<nowiki>"</nowiki>


===Systemic thrombolysis===
|}
* A Cochrane [[meta-analysis]] of [[randomized controlled trials]] showed reduced incidence of [[post-thrombotic syndrome]] and increased the vein patency, but it was associated with increased risk of bleeding.<ref name="pmid15495034">{{cite journal |author=Watson L, Armon M |title=Thrombolysis for acute deep vein thrombosis |journal=Cochrane Database Syst Rev|volume=|issue= |pages=CD002783 |year= |id=PMID 15495034}}</ref>
* Conditions where systemic thrombolysis may be considered are similar to those mentioned in catheter-directed thrombolysis.
* Further, ACCP<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest|volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref> recommends using catheter-directed thrombolysis over systemic thrombolysis if resources and expertise is available.
* '''Major contraindications'''
** Structural intracranial disease
** Previous intracranial hemorrhage
** Ischemic stroke within 3 mo
** Active bleeding
** Recent brain or spinal surgery
** Recent head trauma with fracture or brain injury
** Bleeding diathesis


* '''Relative contraindications'''
===Long-Term Anticoagulation Therapy for Patients With IFDVT (DO NOT EDIT)<ref name="pmid21422387">{{cite journal| author=Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ et al.| title=Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. | journal=Circulation | year= 2011 | volume= 123 | issue= 16 | pages= 1788-830 | pmid=21422387 | doi=10.1161/CIR.0b013e318214914f | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21422387  }} </ref>===
** Systolic BP >180 mm Hg
** Diastolic BP >110 mm Hg
** Recent bleeding (nonintracranial)
** Recent surgery
** Recent invasive procedure
** Ischemic stroke more that 3 mo previously
** Anticoagulation (eg, VKA therapy)
** Traumatic cardiopulmonary resuscitation
** Pericarditis or pericardial fl uid
** Diabetic retinopathy
** Pregnancy
** Age >75 y
** Low body weight (eg, <60 kg)
** Female sex
** Black race


'''ACCP recommendations<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines|journal=Chest |volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref>:'''
{| class="wikitable"
{{cquote|
|-
'''1.''' In patients with acute proximal DVT of the leg, we suggest anticoagulant therapy alone over systemic thrombolysis (Grade 2C).
| colspan="1" style="text-align:center; background:LightGreen" |[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
|-
| bgcolor="LightGreen" |<nowiki>"</nowiki>'''1.''' Adult patients with IFDVT who receive oral warfarin as first-line long-term anticoagulation therapy should have warfarin overlapped with initial anticoagulation therapy for a minimum of 5 days and until the INR is ≥2.0 for at least 24 hours, and then targeted to an INR of 2.0 to 3.0 ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])''.<nowiki>"</nowiki>


'''2.''' In patients with acute DVT of the leg who undergo thrombosis removal, we recommend the same intensity and duration of anticoagulant therapy as in similar patients who do not undergo thrombosis removal.}}
|-
| bgcolor="LightGreen" |<nowiki>"</nowiki>'''2.''' Patients with first-episode IFDVT related to a major reversible risk factor should have anticoagulation stopped after 3 months ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])''<nowiki>"</nowiki>


|-
| bgcolor="LightGreen" |<nowiki>"</nowiki>'''3.''' Patients with recurrent or unprovoked IFDVT should have at least 6 months of anticoagulation and be considered for indefinite anticoagulation with periodic reassessment of the risks and benefits of continued anticoagulation ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])''<nowiki>"</nowiki>


==Compression stockings==
|-
Three randomized control trial conducted in Europe<ref name="pmid15313740">{{cite journal| author=Prandoni P, Lensing AW, Prins MH, Frulla M, Marchiori A, Bernardi E et al.| title=Below-knee elastic compression stockings to prevent the post-thrombotic syndrome: a randomized, controlled trial. | journal=Ann Intern Med | year= 2004 | volume= 141 | issue= 4 | pages= 249-56 | pmid=15313740 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15313740  }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15656548 Review in: ACP J Club. 2005 Jan-Feb;142(1):7] </ref> <ref name="pmid15765034">{{cite journal| author=Partsch H, Kaulich M, Mayer W| title=Immediate mobilisation in acute vein thrombosis reduces post-thrombotic syndrome. | journal=Int Angiol | year= 2004 | volume= 23 | issue= 3 | pages= 206-12 | pmid=15765034 | doi= | pmc= | url= }} </ref>have found, that after the diagnosis of first-episode of proximal DVT, the daily use of knee-high graduated compression stockings (ECS) for 2 years is associated with marked reductions in the frequency of [[Post-thrombotic syndrome]] (PTS).
| bgcolor="LightGreen" |<nowiki>"</nowiki>'''4.''' Cancer patients with IFDVT should receive LMWH monotherapy for at least 3 to 6 months, or as long as the cancer or its treatment (eg, chemotherapy) is ongoing ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])''<nowiki>"</nowiki>
|}


Elastic [[compression stockings]] should be routinely applied, beginning within 1 month of diagnosis of proximal DVT and continuing for a minimum of 1 year after diagnosis".<ref name="pmid15313740">{{cite journal| author=Prandoni P, Lensing AW, Prins MH, Frulla M, Marchiori A, Bernardi E et al.| title=Below-knee elastic compression stockings to prevent the post-thrombotic syndrome: a randomized, controlled trial. | journal=Ann Intern Med | year= 2004 | volume= 141 | issue= 4 | pages= 249-56 | pmid=15313740 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15313740  }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15656548 Review in: ACP J Club. 2005 Jan-Feb;142(1):7] </ref> The stockings in almost all trials were ''stronger than routine anti-embolism stockings'' and were used with 20-30 mm Hg or 30-40 mm Hg pressure gradient. Most trials used knee-high stockings. A cochrane [[meta-analysis]] of [[randomized controlled trials]] reported a reduced incidence of post-phlebitic syndrome.<ref name="pmid14974060">{{cite journal |author=Kolbach D, Sandbrink M, Hamulyak K, Neumann H, Prins M |title=Non-pharmaceutical measures for prevention of post-thrombotic syndrome |journal=Cochrane Database Syst Rev |volume= |issue= |pages=CD004174 |year= |id=PMID 14974060 | doi = 10.1002/14651858.CD004174.pub2}}</ref> The [[number needed to treat]], that is, to prevent one case of [[post-thrombotic syndrome]] was 4 to 5 patients.<ref name="pmid17003920">{{cite journal |author=Kakkos S, Daskalopoulou S, Daskalopoulos M, Nicolaides A, Geroulakos G |title=Review on the value of graduated elastic compression stockings after deep vein thrombosis |journal=Thromb Haemost |volume=96 |issue=4 |pages=441-5 |year=2006 |id=PMID 17003920}}</ref>
{| class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon" | [[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIa]]
|-
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''1.''' In children with DVT, the use of LMWH monotherapy may be reasonable ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>


=== ACC/AHA Guidelines- Recommendations for Use of Compression Therapy (DO NOT EDIT)===
|}


<ref name="pmid21422387">{{cite journal| author=Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ et al.| title=Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. | journal=Circulation | year= 2011 | volume= 123 | issue= 16 | pages= 1788-830 | pmid=21422387 | doi=10.1161/CIR.0b013e318214914f | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21422387  }} </ref>  
===Use of Compression Therapy (DO NOT EDIT)<ref name="pmid21422387">{{cite journal| author=Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ et al.| title=Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. | journal=Circulation | year= 2011 | volume= 123 | issue= 16 | pages= 1788-830 | pmid=21422387 | doi=10.1161/CIR.0b013e318214914f | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21422387  }} </ref>===


{| class="wikitable"
{| class="wikitable"
|-
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
| colspan="1" style="text-align:center; background:LightGreen" |[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
|-
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' Patients with iliofemoral DVT should wear 30– to 40–mm Hg knee-high graduated ECS on a daily basis for at least 2 years ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''.<nowiki>"</nowiki>
| bgcolor="LightGreen" |<nowiki>"</nowiki>'''1.''' Patients with iliofemoral DVT should wear 30– to 40–mm Hg knee-high graduated ECS on a daily basis for at least 2 years ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''.<nowiki>"</nowiki>
|}
|}


{| class="wikitable"
{| class="wikitable"
|-
|-
| colspan="1" style="text-align:center; background:LemonChiffon"| [[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIa]]
| colspan="1" style="text-align:center; background:LemonChiffon" | [[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIa]]
|-
|-
| bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' In patients with prior iliofemoral DVT and symptomatic PTS, daily use of 30– to 40–mm Hg knee-high graduated ECS is reasonable ([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''.<nowiki>"</nowiki>
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''1.''' In patients with prior iliofemoral DVT and symptomatic PTS, daily use of 30– to 40–mm Hg knee-high graduated ECS is reasonable ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''.<nowiki>"</nowiki>
|}
|}


{| class="wikitable"
{| class="wikitable"
|-
|-
| colspan="1" style="text-align:center; background:LemonChiffon"| [[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIb]]
| colspan="1" style="text-align:center; background:LemonChiffon" | [[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIb]]
|-
|-
| bgcolor="LemonChiffon"|'''1.''' In patients with prior iliofemoral DVT and severe edema, intermittent sequential pneumatic compression followed by daily use of 30– to 40–mm Hg knee-high graduated ECS may be considered ([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''.
| bgcolor="LemonChiffon" |'''1.''' In patients with prior iliofemoral DVT and severe edema, intermittent sequential pneumatic compression followed by daily use of 30– to 40–mm Hg knee-high graduated ECS may be considered ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''.
|}
|}


==Guidelines Resources==
*Guidelines on the management of  Pulmonary embolism: Management of Massive and Submassive Pulmonary Embolism, Iliofemoral Deep Vein Thrombosis, and Chronic Thromboembolic Pulmonary Hypertension<ref name="pmid21422387">{{cite journal| author=Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ et al.| title=Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. | journal=Circulation | year= 2011 | volume= 123 | issue= 16 | pages= 1788-830 | pmid=21422387 | doi=10.1161/CIR.0b013e318214914f | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21422387  }} </ref>
==References==
==References==
{{reflist|2}}
{{reflist|2}}


[[Category:Disease]]
[[Category:Cardiology]]
[[Category:Hematology]]
[[Category:Hematology]]
[[Category:Pulmonology]]
[[Category:Angiology]]
[[Category:Cardiology]]
[[Category:Emergency medicine]]
[[Category:Emergency medicine]]
[[Category:Mature chapter]]
[[Category:Vascular surgery]]
[[Category:Up-To-Date]]
[[Category:Cardiovascular diseases]]


{{WH}}
{{WH}}
{{WS}}
{{WS}}

Latest revision as of 02:21, 11 October 2018


To go back to the wikidoc page on VTE, click here



Resident
Survival
Guide

Editor(s)-In-Chief: The APEX Trial Investigators, C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Cafer Zorkun, M.D., Ph.D. [2] ; Kashish Goel, M.D.; Rim Halaby, M.D. [3]; Syed Hassan A. Kazmi BSc, MD [4] Assistant Editor(s)-In-Chief: Justine Cadet

Deep Vein Thrombosis Microchapters

Home

Patient Information

Overview

Classification

Pathophysiology

Causes

Differentiating Deep vein thrombosis from other Diseases

Epidemiology and Demographics

Risk Factors

Triggers

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Approach

Assessment of Clinical Probability and Risk Scores

Assessment of Probability of Subsequent VTE and Risk Scores

History and Symptoms

Physical Examination

Laboratory Findings

Ultrasound

Venography

CT

MRI

Other Imaging Findings

Treatment

Treatment Approach

Medical Therapy

IVC Filter

Invasive Therapy

Surgery

Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Special Scenario

Upper extremity DVT

Recurrence

Pregnancy

Trials

Landmark Trials

Case Studies

Case #1

Deep vein thrombosis medical therapy On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Deep vein thrombosis medical therapy

CDC on Deep vein thrombosis medical therapy

Deep vein thrombosis medical therapy in the news

Blogs on Deep vein thrombosis medical therapy

Directions to Hospitals Treating Deep vein thrombosis

Risk calculators and risk factors for Deep vein thrombosis medical therapy

For the algorithms about the treatment choices, click here.

Overview

Clinical practice guidelines by the American College of Chest Physicians guide management.[1]

Anticoagulation therapy is the mainstay of the treatment of deep vein thrombosis (DVT). The medical treatment of DVT consists of an initial parenteral anticoagulation therapy and a long term anticoagulation therapy. The primary purpose of treatment is to prevent further clot extension, acute pulmonary embolism, recurrence of thrombosis, and late complications such as post-thrombotic syndrome and chronic thromboembolic pulmonary hypertension. The treatment of DVT with parental anticoagulation should be initiated in case of intermediate or high suspicion of suspected DVT even before the diagnostic confirmatory tests are complete. The choice of parental anticoagulation include: low molecular weight heparin (LMWH), fondaparinux, IV unfractionated heparin (UFH) and SC-UFH; however, the administration of LMWH (once daily rather than twice daily) and fondaparinux is recommended over IV-UFH and SCUFH. Parental anticoagulation therapy should be administered for at least 5 days and until the INR is equal or more than 2 for more than 24 hours. Patients who receive long term therapy with anticoagulation should be assessed regularly for the risks vs benefits of anticoagulation therapy.[2] An abnormal D-dimer level at the end of treatment may signal the need for continued treatment in patients with their first unprovoked proximal DVT.[3]

Parenteral Anticoagulation Therapy

Heparin

  • Heparin binds to the enzyme inhibitor antithrombin III (AT). The activated AT then inactivates thrombin and other proteases involved in blood clotting, most notably factor Xa.

Heparin Dosage

Shown below is a table depicting the dosage of heparin for the treatment of DVT. Note that the dose of heparin used in the treatment of acute coronary syndrome is lower than that used for the treatment of PE.[4]

Mode of administration of Heparin Dosage
IV injection 80 U/kg as bolus, followed by 18 U/kg/h, OR

70 U/kg as bolus, followed by 15 U/kg/h for stroke or cardiac patients[5]

SC injection 333 U/kg as bolus, followed by 250 U/kg[5]

Adjustment of Heparin Dosage According to aPTT

aPTT should be monitored during treatment with heparin. Prolongation of apTT correlates with an elevated serum concentration of heparin and requires adjustment of the dosage. Shown below is a table depicting the variation in the dosage according the aPTT.

aPTT Variation in the dosage[6]
< 1.2 x control (<35 s) Bolus: 80 U/kg
Infusion rate: increase by 4 U/kg/h
1.2-1.5 x control (35-45 s) Bolus: 40 U/kg
Infusion rate: increase by 2 U/kg/h
1.5-2.3 x control (46-70 s) Continue the same dosage
2.3-3.0 x control (71-90 s) Infusion rate: decrease by 2 U/kg/h
> 3.0 x control (>90s) Stop infusion for a period of 1 hour, then
Infusion rate: decrease by 3 U/kg/h

Platelet Monitoring

Among patients started on heparin, if the risk of heparin induced thrombocytopenia is more than 1%, monitor platelet count every 2 to 3 days from the 4th until the 14th day of treatment or until the discontinuation of heparin.[2]

Low Molecular Weight Heparin

  • LMWH is used as a first line therapy for the initial anticoagulation therapy for DVT.[4]
  • In addition, LMWH can also be used for the long term anticoagulation treatment for DVT, but vitamin K antagonist are recommended as first line therapy. However, among cancer patients with provoked PE, LMWH is the first line therapy for the long term anticoagulation treatment.[4] LMWH is preferred in pregnancy to avoid the known teratogenic effects of warfarin.
  • LMWH is administered subcutaneously and does not require routine coagulation monitoring.
  • The recommended doses for treatment of DVT are:[4]
    • Enoxaparin : 1 mg/Kg body weight (twice daily) OR 1.5 mg/kg once daily
    • Tinzaparin : 175 U/Kg body weight (once daily)

Fondaparinux

  • Fondaparinux is used as a first line therapy for the initial anticoagulation therapy for DVT. The antithrombotic activity of fondaparinux sodium is the result of antithrombin III (ATIII)-mediated selective inhibition of factor Xa. Fondaparinux does not require routine coagulation monitoring.
  • Recommended doses for the treatment of DVT depend on the weight of the patient:
    • Weight <50 Kg: 5 mg (once daily)
    • Weight between 50 Kg to 100 Kg: 7.5 mg (once daily)
    • Weight >100 Kg: 10 mg (once daily)

Oral Anticoagulation Therapy

Vitamin K Antagonist

  • Warfarin should not be administered in pregnancy and LMWH should be used instead.
  • Warfarin should be started as soon as possible following the initiation of parenteral anticoagulation therapy, preferably at the same day. Parenteral anticoagulation therapy should be continued for at least 5 days concomitantly with warfarin and until INR is ≥ 2 for more than 24 hours.[2]
  • Warfarin is administered as follows:
    • Begin with 5 mg warfarin for 2 days followed by dosing based on the INR.
    • Target INR is 2-3.
    • Monitor INR monthly.
    • If the INR is stable but there is one value 0.5 below or above the target range, continue the same dose and repeat INR within 1-2 weeks.
  • NSAIDs, COX2 selective NSAIDs and some antibiotics should be avoided when warfarin is administered.[5]

Factor X Inhibitors

Rivaroxaban is an oral factor X inhibitors that can be used in the long term treatment of DVT.

Direct Thrombin Inhibitors

Dabigatran is an oral direct thrombin inhibitors that can be used in the long term treatment of DVT.

Thrombolysis

Thrombolysis can refer to either systemic thrombolysis or catheter directed thrombolysis. To read more about catheter directed thrombolysis, click here.

Indications

  • A Cochrane meta-analysis of randomized controlled trials showed reduced incidence of post-thrombotic syndrome and increased the vein patency, but it was associated with increased risk of bleeding.[7]
  • Anticoagulation therapy is preferred over thrombolytic therapy in acute proximal DVT of the leg as well as in upper extremity DVT.
  • According to ACCP guidelines, thrombolysis may be considered only in patients who meet all of the following criteria:[2]
    • Iliofemoral DVT
    • Symptoms < 14 days
    • Good functional status
    • Life expectancy ≥1 year
    • Low risk of bleeding
  • Further, ACCP recommends using catheter-directed thrombolysis over systemic thrombolysis if resources and expertise is available.[2]

Contraindications

Shown below is a table summarizing the absolute and relative contraindications to fibrinolytic therapy among pulmonary embolism patients.[6]

Absolute contraindications Relative contraindications
❑ Previous hemorrhagic stroke or stroke of unknown origin

Ischemic stroke within the last 6 months
Central nervous system tumor or damage
❑ Major trauma, head injury, or surgery within the last 3 weeks
Gastrointestinal bleed within the last month
❑ Known bleeding

Transient ischemic attack within the last 6 months

Oral anticoagulant therapy intake
❑ Advanced liver disease
Infective endocarditis
Peptic ulcer disease that is currently active
Pregnancy or within 1 week post partum
❑ Punctures that are non-compressible
Traumatic resuscitation
Systolic blood pressure >180 mmHg refractory to treatment

Compression Stockings

  • The daily use of knee-high elastic graduated compression stockings (EGCS) for 2 years following the diagnosis of first-episode of proximal DVT is associated with marked reductions in the frequency of Post-thrombotic syndrome (PTS).[8] [9]

Contraindicated Medications

Deep vein thrombosis is considered an absolute contraindication to the use of the following medications:

2016 American College of Chest Physicians Evidence-Based Clinical Practice Guidelines on Antithrombotic Therapy for VTE Disease: Antithrombotic Therapy and Prevention of Thrombosis (DO NOT EDIT)[2]

Initial Choice of Treatment in Patients with Acute DVT of the Leg (DO NOT EDIT)[12]

Grade 1
"1. In patients with acute DVT of the leg, we recommend early initiation of VKA (eg, same day as parenteral therapy is started) over delayed initiation, and continuation of parenteral anticoagulation for a minimum of 5 days and until the international normalized ratio (INR) is 2.0 or above for at least 24 h (Level of evidence B)"
"2. In patients with acute DVT of the leg and whose home circumstances are adequate, we recommend initial treatment at home over treatment in hospital (Level of evidence B)."
"3. In patients with acute DVT of the leg who undergo thrombosis removal, we recommend the same intensity and duration of anticoagulant therapy as in comparable patients who do not undergo thrombosis removal (Level of evidence B)."
"4. In patients with acute DVT of the leg, we recommend against the use of an inferior vena cava (IVC) filter in addition to anticoagulants (Level of evidence B)."
"5. In patients with acute proximal DVT of the leg and contraindication to anticoagulation, we recommend the use of an IVC filter (Level of evidence B)."
Grade 2
"1. In patients with acute DVT of the leg, we suggest LMWH or fondaparinux over IV UFH (Level of evidence C) and over SC UFH (Level of evidence B) for LMWH;(Level of evidence C) for fondaparinux)."
"2. In patients with acute DVT of the leg treated with LMWH, we suggest once- over twice-daily administration (Level of evidence C)."
"3. In patients with acute proximal DVT of the leg, we suggest anti coagulant therapy alone over catheter-directed thrombolysis (CDT) (Level of evidence C)."
"4. In patients with acute proximal DVT of the leg, we suggest anticoagulant therapy alone over systemic thrombolysis (Level of evidence C)."
"5. In patients with acute proximal DVT of the leg, we suggest anticoagulant therapy alone over operative venous thrombectomy (Level of evidence C)."
"6. In patients with acute proximal DVT of the leg and an IVC filter inserted as an alternative to anticoagulation, we suggest a conventional course of anticoagulant therapy if their risk of bleeding resolves (Level of evidence B)."
"7. In patients with acute DVT of the leg, we suggest early ambulation over initial bed rest (Level of evidence C)."

Duration of Anticoagulant Therapy (DO NOT EDIT)[12]

Grade 1
"1. In patients with acute VTE who are treated with anticoagulant therapy, we recommend long-term therapy over stopping anticoagulant therapy after about 1 week of initial therapy (Level of evidence B)"
"2. In patients with a proximal DVT of the leg provoked by surgery, we recommend treatment with anticoagulation for 3 months over (i) treatment of a shorter period (Level of evidence B)" , (ii) treatment of a longer time-limited period (eg, 6 or 12 months) (Level of evidence B) , or (iii) extended therapy (Level of evidence B regardless of bleeding risk)."
"3. In patients with a proximal DVT of the leg provoked by a nonsurgical transient risk factor, we recommend treatment with anticoagulation for 3 months over (i) treatment of a shorter period (Level of evidence B) , (ii) treatment of a longer time-limited period (eg, 6 or 12 months) (Level of evidence B), and (iii) extended therapy if there is a high bleeding risk (Level of evidence B) ."
"4. In patients with an isolated distal DVT of the leg provoked by surgery or by a nonsurgical transient risk factor , we recommend treatment with anticoagulation for 3 months over treatment of a longer time-limited period (eg, 6 or 12 months) (Level of evidence B) or extended therapy (Level of evidence B) regardless of bleeding risk. "
"5. In patients with an unprovoked DVT of the leg (isolated distal or proximal), we recommend treatment with anticoagulation for at least 3 months over treatment of a shorter duration (Level of evidence B) . After 3 months of treatment, patients with unprovoked DVT of the leg should be evaluated for the risk-benefit ratio of extended therapy. "
"6. Anticoagulation should be given for 3 months in patients with a first unprovoked VTE and a high risk of bleeding (Level of Evidence B), but should be extended without a scheduled stop date in patients with a low or moderate risk of bleeding (Level of Evidence B).
"7. In patients with a first VTE that is an unprovoked proximal DVT of the leg and who have a high bleeding risk, we recommend 3 months of anticoagulant therapy over extended therapy (Level of evidence B). "
"8. In patients with a first VTE that is an unprovoked isolated distal DVT of the leg, we recommend 3 months of anticoagulant treatment in those with a high bleeding risk (Level of evidence B)."
"9. In patients with a second unprovoked VTE, we recommend extended anticoagulant therapy over 3 months of therapy in those who have a low bleeding risk (Level of evidence B)".
"10. In all patients who receive extended anticoagulant therapy, the continuing use of treatment should be reassessed at periodic intervals (eg, annually)."
"11. In patients with DVT of the leg and active cancer, if the risk of bleeding is not high, we recommend extended anticoagulant therapy over 3 months of therapy (Level of evidence B)".
Grade 2
"1. In patients with DVT of the leg and active cancer, if there is a high bleeding risk, we suggest extended anticoagulant therapy (Level of evidence B)."
"2. In patients with a first VTE that is an unprovoked proximal DVT of the leg and who have a low or moderate bleeding risk, we suggest extended anticoagulant therapy over 3 months of therapy (Level of evidence B)."
"3. In patients with a second unprovoked VTE who have a high bleeding risk, we suggest 3 months of anticoagulant therapy over extended therapy (Level of evidence B)."
"4. In patients with a proximal DVT of the leg provoked by a nonsurgical transient risk factor,We suggest treatment with anticoagulation for 3 months over extended therapy if there is a low or moderate bleeding risk (Level of evidence B)."
"5.In patients with an isolated distal DVT of the leg provoked by surgery or by a nonsurgical transient risk factor , we suggest treatment with anticoagulation for 3 months over treatment of a shorter period (Level of evidence C). "
"6. In patients with a first VTE that is an unprovoked isolated distal DVT of the leg, we suggest 3 months of anticoagulant therapy over extended therapy in those with a low or moderate bleeding risk (Level of evidence B)."
"7. In patients with a second unprovoked VTE, we suggest extended anticoagulant therapy in those with a moderate bleeding risk (Level of evidence B). "

Duration of Anticoagulant Therapy (DO NOT EDIT)[13]

Class I
"1. Adult patients with IFDVT who receive oral warfarin as first-line long-term anticoagulation therapy should have warfarin overlapped with initial anticoagulation therapy for a minimum of 5 days and until the INR is ≥2.0 for at least 24 hours, and then targeted to an INR of 2.0 to 3.0 (Level of Evidence: A) "
"2. Patients with first-episode IFDVT related to a major reversible risk factor should have anticoagulation stopped after 3 months (Level of Evidence: A)."
"3. Patients with recurrent or unprovoked IFDVT should have at least 6 months of anticoagulation and be considered for indefinite anticoagulation with periodic reassessment of the risks and benefits of continued anticoagulation (Level of Evidence: A)."
"4. Cancer patients with IFDVT should receive LMWH monotherapy for at least 3 to 6 months, or as long as the cancer or its treatment (eg, chemotherapy) is ongoing (Level of Evidence: A). "
Class IIb
"1. In children with DVT, the use of LMWH monotherapy may be reasonable (Level of Evidence: C). "

Intensity of Anticoagulant Effect (DO NOT EDIT)[12]

Grade 1
"1.In patients with DVT of the leg who are treated with VKA, we recommend a therapeutic INR range of 2.0 to 3.0 (target INR of 2.5) over a lower (INR <2) or higher (INR 3.0-5.0) range for all treatment durations (Level of evidence B)".

Treatment of Isolated Distal DVT (DO NOT EDIT)[12]

Grade 1
"1. In patients with acute isolated distal DVT of the leg who are managed with initial anticoagulation, we recommend using the same approach as for patients with acute proximal DVT (Level of evidence B). "
"2. In patients with acute isolated distal DVT of the leg who are managed with serial imaging, we recommend no anticoagulation if the thrombus does not extend (Level of evidence B) ; we recommend anticoagulation if the thrombus extends into the proximal veins (Level of evidence B). "
Grade 2
"1. In patients with acute isolated distal DVT of the leg and without severe symptoms or risk factors for extension, we suggest serial imaging of the deep veins for 2 weeks over initial anticoagulation (Level of evidence C)."
"2. In patients with acute isolated distal DVT of the leg and severe symptoms or risk factors for extension (see text), we suggest initial anticoagulation over serial imaging of the deep veins (Level of evidence C)."
"3. In patients with acute isolated distal DVT of the leg who are managed with serial imaging, we suggest anticoagulation if the thrombus extends but remains confined to the distal veins (Level of evidence C)."

Treatment of Asymptomatic DVT of the Leg (DO NOT EDIT)[12]

Grade 2
"1. In patients who are incidentally found to have asymptomatic DVT of the leg, we suggest the same initial and long-term anticoagulation as for comparable patients with symptomatic DVT (Level of evidence B)".

Treatment of Acute Upper Extremity DVT (DO NOT EDIT)[12]

Grade 1
"1. In patients with UEDVT who undergo thrombolysis, we recommend the same intensity and duration of anticoagulant therapy as in similar patients who do not undergo thrombolysis. (Level of evidence B) "
Grade 2
"1. In patients with acute UEDVT that involves the axillary or more proximal veins, we suggest anticoagulant therapy alone over thrombolysis. (Level of evidence C) ".

Treatment in Special Situations (DO NOT EDIT)[12]

Grade 2
"1. In patients with VTE without an associated cancer diagnosis, all direct oral anticoagulants (dabigatran, rivaroxaban, apixaban, or edoxaban) are recommended over vitamin K antagonist (VKA) therapy (Level of Evidence: B) and VKA therapy is recommended over low molecular weight heparin (LMWH; Level of Evidence: C).
"2. In patients with DVT of the leg and cancer, we suggest LMWH over VKA therapy (Level of evidence B). In patients with DVT and cancer who are not treated with LMWH, we suggest VKA over dabigatran or rivaroxaban for long-term therapy (Level of evidence B).
"3. In patients with DVT of the leg who receive extended therapy, we suggest treatment with the same anticoagulant chosen for the first 3 months (Level of evidence C).

Post-Thrombotic Syndrome (DO NOT EDIT)[12]

Grade 2
"1. In patients with acute DVT, the guideline recommends against the use of compression stockings routinely to prevent the post-thrombotic syndrome (Level of evidence B). "
"2. In patients with PTS of the leg, we suggest a trial of compression stockings (Level of evidence C). "
"3. In patients with severe PTS of the leg that is not adequately relieved by compression stockings, we suggest a trial of an intermittent compression device (Level of evidence B). "
"4. In patients with PTS of the leg, we suggest that venoactive medications (eg, rutosides, defibrotide, and hidrosmin) not be used (Level of evidence C). "

Subsegmental PE Without DVT

Grade 2
"'1.For patient with subsegmental PE and no DVT, the guideline suggests clinical surveillance over anticoagulation when the risk of VTE recurrence is low (Level of Evidence C). The guideline recommends the use of anticoagulation over surveillance when the risk of VTE recurrence is high (Level of Evidence C). "

Prevention of Recurrent VTE after unprovoked Proximal DVT or PE

Grade 2
"1.For patients with an unprovoked proximal DVT or PE who are stopping anticoagulant therapy, the guideline suggests the use of aspirin over no aspirin to prevent recurrent VTE if there are no contraindications to aspirin therapy (Level of evidence B). "

Recurrent VTE while on Non-LMWH Anticoagulant

Grade 2
"'1.For patients with recurrent VTE while treated with a non-LMWH anticoagulant, the guideline recommends changing to LMWH therapy (Level of Evidence C). If patients suffer a recurrent VTE while on LMWH treatment, the guideline recommends increasing the LMWH dose (Level of Evidence C). "

2011 AHA Scientific Statement- Management of Massive and Submassive Pulmonary Embolism, Iliofemoral Deep Vein Thrombosis, and Chronic Thromboembolic Pulmonary Hypertension (DO NOT EDIT)[13]

Anticoagulation for Patients With IFDVT (DO NOT EDIT)[13]

Class I
"1. In the absence of suspected or proven heparin-induced thrombocytopenia, patients with IFDVT should receive therapeutic anticoagulation with either intravenous UFH (Level of Evidence: A), UFH by subcutaneous injection (Level of Evidence: B), an LMWH (Level of Evidence: A), or fondaparinux (Level of Evidence: A)."
"2. Patients with IFDVT who have suspected or proven heparin-induced thrombocytopenia should receive a direct thrombin inhibitor (Level of Evidence: B)"

Long-Term Anticoagulation Therapy for Patients With IFDVT (DO NOT EDIT)[13]

Class I
"1. Adult patients with IFDVT who receive oral warfarin as first-line long-term anticoagulation therapy should have warfarin overlapped with initial anticoagulation therapy for a minimum of 5 days and until the INR is ≥2.0 for at least 24 hours, and then targeted to an INR of 2.0 to 3.0 (Level of Evidence: A)."
"2. Patients with first-episode IFDVT related to a major reversible risk factor should have anticoagulation stopped after 3 months (Level of Evidence: A)"
"3. Patients with recurrent or unprovoked IFDVT should have at least 6 months of anticoagulation and be considered for indefinite anticoagulation with periodic reassessment of the risks and benefits of continued anticoagulation (Level of Evidence: A)"
"4. Cancer patients with IFDVT should receive LMWH monotherapy for at least 3 to 6 months, or as long as the cancer or its treatment (eg, chemotherapy) is ongoing (Level of Evidence: A)"
Class IIa
"1. In children with DVT, the use of LMWH monotherapy may be reasonable (Level of Evidence: C)"

Use of Compression Therapy (DO NOT EDIT)[13]

Class I
"1. Patients with iliofemoral DVT should wear 30– to 40–mm Hg knee-high graduated ECS on a daily basis for at least 2 years (Level of Evidence: B)."
Class IIa
"1. In patients with prior iliofemoral DVT and symptomatic PTS, daily use of 30– to 40–mm Hg knee-high graduated ECS is reasonable (Level of Evidence: C)."
Class IIb
1. In patients with prior iliofemoral DVT and severe edema, intermittent sequential pneumatic compression followed by daily use of 30– to 40–mm Hg knee-high graduated ECS may be considered (Level of Evidence: B).

References

  1. Kearon C, Akl EA, Ornelas J, Blaivas A, Jimenez D, Bounameaux H; et al. (2016). "Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report". Chest. 149 (2): 315–52. doi:10.1016/j.chest.2015.11.026. PMID 26867832.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 2.6 Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ; et al. (2012). "Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines". Chest. 141 (2 Suppl): e419S–94S. doi:10.1378/chest.11-2301. PMC 3278049. PMID 22315268.
  3. Palareti G, Cosmi B, Legnani C, Tosetto A, Brusi C, Iorio A; et al. (2006). "D-dimer testing to determine the duration of anticoagulation therapy". N Engl J Med. 355 (17): 1780–9. doi:10.1056/NEJMoa054444. PMID 17065639. Review in: Evid Based Med. 2007 Apr;12(2):45 Review in: ACP J Club. 2007 Mar-Apr;146(2):29
  4. 4.0 4.1 4.2 4.3 4.4 4.5 Garcia DA, Baglin TP, Weitz JI, Samama MM (2012). "Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines". Chest. 141 (2 Suppl): e24S–43S. doi:10.1378/chest.11-2291. PMID 22315264. Unknown parameter |month= ignored (help)
  5. 5.0 5.1 5.2 Holbrook A, Schulman S, Witt DM, Vandvik PO, Fish J, Kovacs MJ; et al. (2012). "Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines". Chest. 141 (2 Suppl): e152S–84S. doi:10.1378/chest.11-2295. PMC 3278055. PMID 22315259.
  6. 6.0 6.1 Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P; et al. (2008). "Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC)". Eur Heart J. 29 (18): 2276–315. doi:10.1093/eurheartj/ehn310. PMID 18757870.
  7. Watson L, Armon M. "Thrombolysis for acute deep vein thrombosis". Cochrane Database Syst Rev: CD002783. PMID 15495034.
  8. 8.0 8.1 Prandoni P, Lensing AW, Prins MH, Frulla M, Marchiori A, Bernardi E; et al. (2004). "Below-knee elastic compression stockings to prevent the post-thrombotic syndrome: a randomized, controlled trial". Ann Intern Med. 141 (4): 249–56. PMID 15313740. Review in: ACP J Club. 2005 Jan-Feb;142(1):7
  9. Partsch H, Kaulich M, Mayer W (2004). "Immediate mobilisation in acute vein thrombosis reduces post-thrombotic syndrome". Int Angiol. 23 (3): 206–12. PMID 15765034.
  10. Kolbach D, Sandbrink M, Hamulyak K, Neumann H, Prins M. "Non-pharmaceutical measures for prevention of post-thrombotic syndrome". Cochrane Database Syst Rev: CD004174. doi:10.1002/14651858.CD004174.pub2. PMID 14974060.
  11. Kakkos S, Daskalopoulou S, Daskalopoulos M, Nicolaides A, Geroulakos G (2006). "Review on the value of graduated elastic compression stockings after deep vein thrombosis". Thromb Haemost. 96 (4): 441–5. PMID 17003920.
  12. 12.0 12.1 12.2 12.3 12.4 12.5 12.6 12.7 Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ (2012). "Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines". Chest. 141 (2 Suppl): 7S–47S. doi:10.1378/chest.1412S3. PMID 22315257. Unknown parameter |month= ignored (help)
  13. 13.0 13.1 13.2 13.3 13.4 Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ, Jenkins JS, Kline JA, Michaels AD, Thistlethwaite P, Vedantham S, White RJ, Zierler BK (2011). "Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association". Circulation. 123 (16): 1788–830. doi:10.1161/CIR.0b013e318214914f. PMID 21422387. Retrieved 2012-02-11. Unknown parameter |month= ignored (help)

Template:WH Template:WS