Deep vein thrombosis medical therapy: Difference between revisions
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** [[Post-thrombotic syndrome]] | ** [[Post-thrombotic syndrome]] | ||
** Chronic thromboembolic pulmonary hypertension. | ** Chronic thromboembolic pulmonary hypertension. | ||
==Key Guidelines for Thrombolytic Therapy : ACCP Guidelines== | |||
; Extensive iliofemoral DVT | |||
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| colspan="1" style="text-align:center; background:LemonChiffon"|Class II Recommendations | |||
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* Catheter directed thrombolysis. (Grade C recommendation) | |||
** It is preferred over open throbectomy. | |||
** Systemic thrombolytics may be useful. | |||
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|bgcolor="LemonChiffon"| Mechanical thrombectomy to shorten lytic exposure. | |||
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|bgcolor="LemonChiffon"| PTA/Stenting to relief underlying venous lesion. | |||
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==Anticoagulation== | ==Anticoagulation== | ||
Revision as of 03:20, 8 October 2012
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] Ujjwal Rastogi, MBBS [3]; Kashish Goel, M.D.; Assistant Editor(s)-In-Chief: Justine Cadet
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Deep Vein Thrombosis Microchapters |
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Diagnosis |
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Treatment |
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Special Scenario |
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Trials |
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Case Studies |
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Deep vein thrombosis medical therapy On the Web |
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Risk calculators and risk factors for Deep vein thrombosis medical therapy |
Overview
An approach to the treatment of DVT has been described here. The primary purpose of treatment is to prevent the following:
- Further clot extension,
- Acute Pulmonary embolism,
- Recurrence of thrombosis,
- Prevention of late complications such as:
- Post-thrombotic syndrome
- Chronic thromboembolic pulmonary hypertension.
Key Guidelines for Thrombolytic Therapy : ACCP Guidelines
- Extensive iliofemoral DVT
| Class II Recommendations |
|
| Mechanical thrombectomy to shorten lytic exposure.
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| PTA/Stenting to relief underlying venous lesion. |
Anticoagulation
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.[1] 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.[2]
Parenteral Anticoagulants
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.
- 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.
Low molecular weight heparin
- 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
- 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
- Direct thrombin inhibitors bind to thrombin and block its activity. These include Hirudin, bivalurudin, and argatroban.
Hirudin
- 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.
- 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
- 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.
- 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.
Warfarin
Direct factor Xa inhibitor
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[4]. 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.
Thrombolysis
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[5], 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[5]:
| “ |
1. In patients with acute proximal DVT of the leg, we suggest anticoagulant therapy alone over CDT (Grade 2C). 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. |
” |
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.[6]
- Conditions where systemic thrombolysis may be considered are similar to those mentioned in catheter-directed thrombolysis.
- Further, ACCP[5] 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
- 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[5]:
| “ |
1. In patients with acute proximal DVT of the leg, we suggest anticoagulant therapy alone over systemic thrombolysis (Grade 2C). 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. |
” |
Compression stockings
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".[7] 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.[8] The number needed to treat, that is, to prevent one case of post-thrombotic syndrome was 4 to 5 patients.[9]
References
- ↑ 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
- ↑ Kearon C, Kahn SR, Agnelli G, Goldhaber S, Raskob GE, Comerota AJ (2008). "Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)". Chest. 133 (6 Suppl): 454S–545S. doi:10.1378/chest.08-0658. PMID 18574272. Retrieved 2012-01-11. Unknown parameter
|month=ignored (help) - ↑ 3.0 3.1 3.2 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) - ↑ Bauersachs R, Berkowitz SD, Brenner B; et al. (2010). "Oral rivaroxaban for symptomatic venous thromboembolism". N. Engl. J. Med. 363 (26): 2499–510. doi:10.1056/NEJMoa1007903. PMID 21128814. Unknown parameter
|month=ignored (help) - ↑ 5.0 5.1 5.2 5.3 Kearon C, Akl EA, Comerota AJ; 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. PMID 22315268. Unknown parameter
|month=ignored (help) - ↑ Watson L, Armon M. "Thrombolysis for acute deep vein thrombosis". Cochrane Database Syst Rev: CD002783. PMID 15495034.
- ↑ 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
- ↑ 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.
- ↑ 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.