Thrombophilia natural history, complications and prognosis: Difference between revisions

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==Overview==
==Overview==
* Due to the multitude and complexity of inherited thrombophilias, the true [[prevalence]] is unknown, and current data may be providing an underestimate. Comparison among different epidemiologic studies becomes difficult due to variation in study design and inclusion criteria.
The annual thrombotic risks are variable and depend on the underlying thrombophilia.<ref name="pmid11529700">{{cite journal| author=Bauer KA| title=The thrombophilias: well-defined risk factors with uncertain therapeutic implications. | journal=Ann Intern Med | year= 2001 | volume= 135 | issue= 5 | pages= 367-73 | pmid=11529700 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11529700 }} </ref>  
* Prevalence of common inherited thrombophilias is variable among both healthy patients and patients with recurrent [[thrombosis]].  
* According to epidemiologic and modeling studies obtained from certain sources<ref name="pmid26780744">{{cite journal| author=Stevens SM, Woller SC, Bauer KA, Kasthuri R, Cushman M, Streiff M et al.| title=Guidance for the evaluation and treatment of hereditary and acquired thrombophilia. | journal=J Thromb Thrombolysis | year= 2016 | volume= 41 | issue= 1 | pages= 154-64 | pmid=26780744 | doi=10.1007/s11239-015-1316-1 | pmc=4715840 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26780744  }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638  }} </ref>, the prevalence of inherited thrombophilias was estimated to be between 0.01-7% in caucasians.
* In certain studies, the prevalence of inherited thrombophilias, specifically, '''activated protein C resistance''' and '''prothrombin G20210A''', rises to approximately 10-60% in patients with documented venous thrombosis compared to less than 10% among controls<ref name="pmid9669991">{{cite journal| author=Margaglione M, Brancaccio V, Giuliani N, D'Andrea G, Cappucci G, Iannaccone L et al.| title=Increased risk for venous thrombosis in carriers of the prothrombin G-->A20210 gene variant. | journal=Ann Intern Med | year= 1998 | volume= 129 | issue= 2 | pages= 89-93 | pmid=9669991 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9669991  }} </ref><ref name="pmid7877648">{{cite journal| author=Ridker PM, Hennekens CH, Lindpaintner K, Stampfer MJ, Eisenberg PR, Miletich JP| title=Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke, and venous thrombosis in apparently healthy men. | journal=N Engl J Med | year= 1995 | volume= 332 | issue= 14 | pages= 912-7 | pmid=7877648 | doi=10.1056/NEJM199504063321403 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7877648  }} </ref><ref name="pmid7902898">{{cite journal| author=Koster T, Rosendaal FR, de Ronde H, Briët E, Vandenbroucke JP, Bertina RM| title=Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden Thrombophilia Study. | journal=Lancet | year= 1993 | volume= 342 | issue= 8886-8887 | pages= 1503-6 | pmid=7902898 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7902898  }} </ref>.
* The incidence of inherited thrombophilia in incident venous thrombosis is approximately 150-840 per 100,000 person years<ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360  }} </ref>.
* The incidence of inherited thrombophilia in recurrent venous thrombosis is approximately 3,500-10,500 per 100,000 person-years<ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360  }} </ref>.
===Age===
*Patients of all age groups may develop thrombophilias. 
*Acquired thrombophilias are more commonly observed among elderly patients (age > 60) as age is a risk factor for thrombosis.
*Inherited thrombophilias can be seen among young patients aged <40-55 years old.
===Gender===
*Epidemiologic studies have provided mixed results regarding the effect of gender on venous thrombosis. Certain groups observed increased risk of thrombosis in younger females and older males, whereas other groups found similar frequencies in both genders<ref name="pmid12814979">{{cite journal| author=White RH| title=The epidemiology of venous thromboembolism. | journal=Circulation | year= 2003 | volume= 107 | issue= 23 Suppl 1 | pages= I4-8 | pmid=12814979 | doi=10.1161/01.CIR.0000078468.11849.66 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12814979  }} </ref>.
*A prospective follow up study performed by Christiansen et al, revealed an age corrected hazard ratio of 2.7 of recurrent thrombosis in male patients with inherited thrombophilias compared to women<ref name="pmid15900005">{{cite journal| author=Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR| title=Thrombophilia, clinical factors, and recurrent venous thrombotic events. | journal=JAMA | year= 2005 | volume= 293 | issue= 19 | pages= 2352-61 | pmid=15900005 | doi=10.1001/jama.293.19.2352 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15900005  }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213089 Review in: Evid Based Med. 2006 Apr;11(2):59] </ref>.
*In patients with inherited thrombophilias, a prospective follow up study performed by Christiansen et al revealed an age corrected hazard ratio of 2.7 for recurrent thrombosis in male patients compared to women<ref name="pmid15900005">{{cite journal| author=Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR| title=Thrombophilia, clinical factors, and recurrent venous thrombotic events. | journal=JAMA | year= 2005 | volume= 293 | issue= 19 | pages= 2352-61 | pmid=15900005 | doi=10.1001/jama.293.19.2352 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15900005  }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213089 Review in: Evid Based Med. 2006 Apr;11(2):59] </ref>.
===Race===
* The factor V leiden G1691A and prothrombin G20210A mutations are exceedingly rare in non-white populations<ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref>.


==Epidemiology and Demographics==
==Natural History==
===Prevalence of select inherited thrombophilias among whites===
*[[Factor V Leiden]] and [[Prothrombin G20210A]]: If left untreated, the annual incidence of incident thrombosis in asymptomatic patients is low (<0.06%). However, the occurrence of recurrent thrombosis can not be predicted in such inherited thrombophilias. <ref name="pmid15254285">{{cite journal| author=Bates SM, Ginsberg JS| title=Clinical practice. Treatment of deep-vein thrombosis. | journal=N Engl J Med | year= 2004 | volume= 351 | issue= 3 | pages= 268-77 | pmid=15254285 | doi=10.1056/NEJMcp031676 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15254285  }} </ref><ref name="pmid15900005">{{cite journal| author=Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR| title=Thrombophilia, clinical factors, and recurrent venous thrombotic events. | journal=JAMA | year= 2005 | volume= 293 | issue= 19 | pages= 2352-61 | pmid=15900005 | doi=10.1001/jama.293.19.2352 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15900005  }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213089 Review in: Evid Based Med. 2006 Apr;11(2):59] </ref><ref name="pmid12932383">{{cite journal| author=Baglin T, Luddington R, Brown K, Baglin C| title=Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study. | journal=Lancet | year= 2003 | volume= 362 | issue= 9383 | pages= 523-6 | pmid=12932383 | doi=10.1016/S0140-6736(03)14111-6 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12932383  }} </ref>
*[[Protein_C|Protein C]], [[Protein_S|Protein S]], and [[Antithrombin]] deficiencies: These conditions carries an increased risk for recurrent thrombosis in untreated patients. <ref name="pmid15900005">{{cite journal| author=Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR| title=Thrombophilia, clinical factors, and recurrent venous thrombotic events. | journal=JAMA | year= 2005 | volume= 293 | issue= 19 | pages= 2352-61 | pmid=15900005 | doi=10.1001/jama.293.19.2352 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15900005  }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213089 Review in: Evid Based Med. 2006 Apr;11(2):59] </ref><ref name="pmid16670075">{{cite journal| author=De Stefano V, Simioni P, Rossi E, Tormene D, Za T, Pagnan A et al.| title=The risk of recurrent venous thromboembolism in patients with inherited deficiency of natural anticoagulants antithrombin, protein C and protein S. | journal=Haematologica | year= 2006 | volume= 91 | issue= 5 | pages= 695-8 | pmid=16670075 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16670075  }} </ref> 
*[[Oral contraceptives]], [[hormone replacement therapy]], and [[pregnancy]] can significantly increase thrombotic risk in patients with underlying thrombophilia.<ref name="pmid18501222">{{cite journal| author=Dalen JE| title=Should patients with venous thromboembolism be screened for thrombophilia? | journal=Am J Med | year= 2008 | volume= 121 | issue= 6 | pages= 458-63 | pmid=18501222 | doi=10.1016/j.amjmed.2007.10.042 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18501222  }} </ref>
*Certain high risk thrombophilias require indefinite [[anticoagulant|anticoagulation]]. However, such patients on preventive oral anticoagulant therapy for venous thromboembolism still carries the annual incidence of significant bleeds of ~2-3%.<ref name="pmid14644891">{{cite journal| author=Linkins LA, Choi PT, Douketis JD| title=Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism: a meta-analysis. | journal=Ann Intern Med | year= 2003 | volume= 139 | issue= 11 | pages= 893-900 | pmid=14644891 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14644891  }} </ref>


{| border="1" cellpadding="5" cellspacing="0" align="center" class="sortable"
==Complications==
*The primary complication of thrombophilia is the development of [[Thrombus|blood clots]], also known as '''thrombus formation'''.
*The most common complications of thrombophilia are as follows: <ref name="pmid11529700">{{cite journal| author=Bauer KA| title=The thrombophilias: well-defined risk factors with uncertain therapeutic implications. | journal=Ann Intern Med | year= 2001 | volume= 135 | issue= 5 | pages= 367-73 | pmid=11529700 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11529700  }} </ref><ref name="pmid15254285">{{cite journal| author=Bates SM, Ginsberg JS| title=Clinical practice. Treatment of deep-vein thrombosis. | journal=N Engl J Med | year= 2004 | volume= 351 | issue= 3 | pages= 268-77 | pmid=15254285 | doi=10.1056/NEJMcp031676 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15254285  }} </ref><ref name="pmid18501222">{{cite journal| author=Dalen JE| title=Should patients with venous thromboembolism be screened for thrombophilia? | journal=Am J Med | year= 2008 | volume= 121 | issue= 6 | pages= 458-63 | pmid=18501222 | doi=10.1016/j.amjmed.2007.10.042 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18501222  }} </ref>
**[[Deep vein thrombosis]]
**[[Pulmonary embolism]]
** Postthrombotic syndrome (PTS) with chronic venous ulceration (CVU) <ref name="pmid23762560">{{cite journal| author=Rabinovich A, Kahn SR| title=Association between Thrombophilia and the Post-Thrombotic Syndrome. | journal=Int J Vasc Med | year= 2013 | volume= 2013 | issue=  | pages= 643036 | pmid=23762560 | doi=10.1155/2013/643036 | pmc=3665186 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23762560  }} </ref>
 
'''Table 1: The risk of future thrombosis in patients with thrombophilia:'''
 
{| class="wikitable"
|-
|-
  ! Inherited thrombophilia
! style="font-weight: bold;" |Thrombotic risk<ref name="pmid15254285">{{cite journal| author=Bates SM, Ginsberg JS| title=Clinical practice. Treatment of deep-vein thrombosis. | journal=N Engl J Med | year= 2004 | volume= 351 | issue= 3 | pages= 268-77 | pmid=15254285 | doi=10.1056/NEJMcp031676 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15254285  }} </ref>
  ! Healthy subjects/General population (%)
!! style="font-weight: bold;" |Thrombophilic state
  ! Patients with recurrent thrombosis (%)
|-
|-
  | [[Factor V Leiden]]
| '''Modest''' || [[Trauma]]/[[General surgery]], [[Elderly|Age > 60]], [[Immobilization]], [[Pregnancy]], [[Hormone therapy|Hormone therapies]], [[Factor V Leiden]] heterozygosity, [[Prothrombin]] mutation, Homocysteinemia, Increased factor VIII levels, Increased factor IX levels, Increased factor XI levels
  | 1 - 20
  | 18 - 50
|-
|-
  | [[Prothrombin]] G20210A
| '''Intermediate''' || Protein C and S deficiency, Dysfibrogenemia
  | 2 - 8
  | 7 - 20
|-
|-
  | [[Antithrombin deficiency]]
| '''High''' || [[Malignancy]], APLS/[[Lupus anticoagulant]], Myeloproliferative disorders/hyperviscosity, PNH, [[Orthopedic surgery]], [[Antithrombin deficiency]], Factor V Leiden homozygosity
  | 0.02-2
|}
  | 1 - 5
 
'''Table 2: The effect of concurrent hormone exposure on incident thrombosis and thrombotic risk in patients with underlying thrombophilia:'''
{| class="wikitable"
! style="font-weight: bold;" | Thrombophilic state
! style="font-weight: bold;" | Annual Incidence (%)
! style="font-weight: bold;" | Relative Risk
|-
|-
  | [[Dysfibrinogenemia]]
| Normal
  | <1
| 0.008
  | <1
| 1
|-
|-
  | [[Protein C deficiency]]
| [[Factor V Leiden]] heterozygous
  | 0.2 - 5
| 0.06
  | 3 - 10
| 3-10
|-
|-
  | [[Protein S deficiency]]
| [[Factor V Leiden]] homozygous
  | 0.3 - 3
| 0.5-1
  | 2 - 10
| 80
|-
|-
  | [[Hyperhomocystenemia]]
| [[Prothrombin G20210A]]
  | <5
| 0.02
  | <10
| 1-5
|-
|-
  | Elevated [[factor VIII]] levels
| [[Oral contraceptive]] (OCP)
  | 11
| 0.03
  | 25
| 4
|-
|-
| OCP and factor V leiden heterozygous
| 0.3
| 35
|-
| OCP and factor V leiden homozygous
|
| 100
|-
| OCP and prothrombin G20210A
|
| 16
|-
| OCP and protein C/S, or antithrombin III deficiency
|
| 9.7
|-
| [[Pregnancy]]
|
| 7
|-
| Pregnancy and factor V leiden heterozygous
| 
| 35
|-
| [[Cancer]]
|
| 5
|-
| History of venous thrombosis
|
| 50
|}
|}


* In African and Asian patients, the prevalence of factor V leiden was approximately 0.05% and the prevalence of prothrombin G20210A was approximately 0.06%.  
==Prognosis==
*The prognosis depends on the underlying thrombophilia as each disorder has a different associated thrombotic risk (Table 1 and 2).
*Thrombophilias associated with the development of multiple or atypical clots, arterial thrombosis, or life-threatening thrombosis carries '''worse prognosis''' which are as follows:
**[[Antiphospholipid Syndrome]]
**[[Paroxysmal nocturnal hemoglobinuria]]
**[[Antithrombin III deficiency]]
**[[Factor V Leiden]] homozygosity
*High risk thrombophilic conditions require consideration for '''lifelong [[anticoagulation]]''' under the supervision of an expert consultant.
**[[Antiphospholipid Syndrome]]
**[[Paroxysmal nocturnal hemoglobinuria]]
**Recurrent thrombosis regardless of underlying thrombophilia
**History of life-threatening thrombosis or atypical locations
**Malignancy with history of thrombosis


This data were consolidated from multiple sources<ref name="pmid11309638">{{cite journal |author=Seligsohn U, Lubetsky A|title=Genetic susceptibility to venous thrombosis |journal=N. Engl. J. Med. |volume=344 |issue=16 |pages=1222–31 |year=2001 |month=April |pmid=11309638|doi=10.1056/NEJM200104193441607 |url=}}</ref><ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360  }} </ref><ref name="pmid12787534">{{cite journal |author=Buchanan GS, Rodgers GM, Ware Branch D |title=The inherited thrombophilias: genetics, epidemiology, and laboratory evaluation |journal=Best Pract Res Clin Obstet Gynaecol |volume=17 |issue=3 |pages=397–411 |year=2003 |month=June |pmid=12787534 |doi= |url=}}</ref><ref name="pmid11702218">{{cite journal |author=Franco RF, Reitsma PH |title=Genetic risk factors of venous thrombosis |journal=Hum. Genet. |volume=109 |issue=4 |pages=369–84 |year=2001 |month=October |pmid=11702218 |doi=10.1007/s004390100593 |url=}}</ref><ref name="pmid7740487">{{cite journal |author=Haverkate F, Samama M |title=Familial dysfibrinogenemia and thrombophilia. Report on a study of the SSC Subcommittee on Fibrinogen |journal=Thromb. Haemost. |volume=73 |issue=1 |pages=151–61 |year=1995 |month=January |pmid=7740487 |doi= |url=}}</ref>
==References==
==References==
{{reflist|2}}
{{reflist|2}}
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[[Category:FinalQCRequired]]
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Latest revision as of 20:14, 12 March 2021

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Asiri Ediriwickrema, M.D., M.H.S. [2] Jaspinder Kaur, MBBS[3]

Overview

The annual thrombotic risks are variable and depend on the underlying thrombophilia.[1]

Natural History

  • Factor V Leiden and Prothrombin G20210A: If left untreated, the annual incidence of incident thrombosis in asymptomatic patients is low (<0.06%). However, the occurrence of recurrent thrombosis can not be predicted in such inherited thrombophilias. [2][3][4]
  • Protein C, Protein S, and Antithrombin deficiencies: These conditions carries an increased risk for recurrent thrombosis in untreated patients. [3][5]
  • Oral contraceptives, hormone replacement therapy, and pregnancy can significantly increase thrombotic risk in patients with underlying thrombophilia.[6]
  • Certain high risk thrombophilias require indefinite anticoagulation. However, such patients on preventive oral anticoagulant therapy for venous thromboembolism still carries the annual incidence of significant bleeds of ~2-3%.[7]

Complications

Table 1: The risk of future thrombosis in patients with thrombophilia:

Thrombotic risk[2] Thrombophilic state
Modest Trauma/General surgery, Age > 60, Immobilization, Pregnancy, Hormone therapies, Factor V Leiden heterozygosity, Prothrombin mutation, Homocysteinemia, Increased factor VIII levels, Increased factor IX levels, Increased factor XI levels
Intermediate Protein C and S deficiency, Dysfibrogenemia
High Malignancy, APLS/Lupus anticoagulant, Myeloproliferative disorders/hyperviscosity, PNH, Orthopedic surgery, Antithrombin deficiency, Factor V Leiden homozygosity

Table 2: The effect of concurrent hormone exposure on incident thrombosis and thrombotic risk in patients with underlying thrombophilia:

Thrombophilic state Annual Incidence (%) Relative Risk
Normal 0.008 1
Factor V Leiden heterozygous 0.06 3-10
Factor V Leiden homozygous 0.5-1 80
Prothrombin G20210A 0.02 1-5
Oral contraceptive (OCP) 0.03 4
OCP and factor V leiden heterozygous 0.3 35
OCP and factor V leiden homozygous 100
OCP and prothrombin G20210A 16
OCP and protein C/S, or antithrombin III deficiency 9.7
Pregnancy 7
Pregnancy and factor V leiden heterozygous 35
Cancer 5
History of venous thrombosis 50

Prognosis

References

  1. ↑ 1.0 1.1 Bauer KA (2001). "The thrombophilias: well-defined risk factors with uncertain therapeutic implications". Ann Intern Med. 135 (5): 367–73. PMID 11529700.
  2. ↑ 2.0 2.1 2.2 Bates SM, Ginsberg JS (2004). "Clinical practice. Treatment of deep-vein thrombosis". N Engl J Med. 351 (3): 268–77. doi:10.1056/NEJMcp031676. PMID 15254285.
  3. ↑ 3.0 3.1 Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR (2005). "Thrombophilia, clinical factors, and recurrent venous thrombotic events". JAMA. 293 (19): 2352–61. doi:10.1001/jama.293.19.2352. PMID 15900005. Review in: Evid Based Med. 2006 Apr;11(2):59
  4. ↑ Baglin T, Luddington R, Brown K, Baglin C (2003). "Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study". Lancet. 362 (9383): 523–6. doi:10.1016/S0140-6736(03)14111-6. PMID 12932383.
  5. ↑ De Stefano V, Simioni P, Rossi E, Tormene D, Za T, Pagnan A; et al. (2006). "The risk of recurrent venous thromboembolism in patients with inherited deficiency of natural anticoagulants antithrombin, protein C and protein S." Haematologica. 91 (5): 695–8. PMID 16670075.
  6. ↑ 6.0 6.1 Dalen JE (2008). "Should patients with venous thromboembolism be screened for thrombophilia?". Am J Med. 121 (6): 458–63. doi:10.1016/j.amjmed.2007.10.042. PMID 18501222.
  7. ↑ Linkins LA, Choi PT, Douketis JD (2003). "Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism: a meta-analysis". Ann Intern Med. 139 (11): 893–900. PMID 14644891.
  8. ↑ Rabinovich A, Kahn SR (2013). "Association between Thrombophilia and the Post-Thrombotic Syndrome". Int J Vasc Med. 2013: 643036. doi:10.1155/2013/643036. PMC 3665186. PMID 23762560.

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