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.
* 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>.


==Natural History==
==Epidemiology and Demographics==
* Refer to the [[Thrombophilia_history_and_symptoms|clinical symptoms]] section regarding early clinical features of patients with thrombophilia.
===Prevalence of select inherited thrombophilias among whites===
* 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>.
* If left untreated, the annual incidence of incident thrombosis in asymptomatic patients with factor V leiden and prothrombin G20210A (<0.06%) is low<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>. The risk is approximately equivalent to treatment with oral contraceptives (OCPs). Whereas the annual incidence of significant bleeds is approximately 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>.
* Studies performed by Christiansen et al and Baglin et al revealed that inherited thrombophilia from factor V leiden and prothrombin G20210A did not predict for recurrent thrombosis<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>.
* Christiansen et al and De Stefano et al observed a mild increased risk for recurrent thrombosis in patients with protein C, protein S and antithrombin deficiency<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>.
* OCPs, hormone replacement therapy, and pregnancy can significantly increase thrombotic risk in patients with 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 indefinate [[anticoagulant|anticoagulation]].


==Complications==
{| border="1" cellpadding="5" cellspacing="0" align="center" class="sortable"
{| class="wikitable"
! style="font-weight: bold;" |Thrombophilic state
! 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>
|-
|-
| Trauma/General surgery
  ! Inherited thrombophilia
| Modest
  ! Healthy subjects/General population (%)
  ! Patients with recurrent thrombosis (%)
|-
|-
| Age > 60
  | [[Factor V Leiden]]
| Modest
  | 1 - 20
  | 18 - 50
|-
|-
| Immobilization
  | [[Prothrombin]] G20210A
| Modest
  | 2 - 8
  | 7 - 20
|-
|-
| Pregnancy
  | [[Antithrombin deficiency]]
| Modest
  | 0.02-2
  | 1 - 5
|-
|-
| Hormone therapies
  | [[Dysfibrinogenemia]]
| Modest
  | <1
  | <1
|-
|-
| Factor V Leiden heterozygosity
  | [[Protein C deficiency]]
| Modest
  | 0.2 - 5
  | 3 - 10
|-
|-
| Prothrombin mutation
  | [[Protein S deficiency]]
| Modest
  | 0.3 - 3
  | 2 - 10
|-
|-
| Homocysteinemia
  | [[Hyperhomocystenemia]]
| Modest
  | <5
  | <10
|-
|-
| Increased factor VIII levels
  | Elevated [[factor VIII]] levels
| Modest
  | 11
|-
  | 25
| Increased factor IX levels
| Modest
|-
| Increased factor XI levels
| Modest
|-
| Protein C and S deficiency
| Intermediate
|-
| Dysfibrogenemia
| Intermediate
|-
| Malignancy
| High
|-
| APLS/Lupus anticoagulant
| High
|-
| Myeloproliferative disorders/hyperviscosity
| High
|-
| PNH
| High
|-
| Orthopedic surgery
| High
|-
| Antithrombin deficiency
| High
|-
| Factor V Leiden homozygosity
| High
|-
|-
|}
|}


'''Modification of thrombotic risk with concurrent hormone exposure.'''
* 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%.  
{| class="wikitable"
! style="font-weight: bold;" | Thrombophilic state
! style="font-weight: bold;" | Annual Incidence (%)
! style="font-weight: bold;" | 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
|-
| style="font-style: italic;" | OCP and factor V leiden heterozygous
| style="font-style: italic;" | 0.3
| style="font-style: italic;" | 35
|-
| style="font-style: italic;" | OCP and factor V leiden homozygous
| style="font-style: italic;" |
| style="font-style: italic;" | 100
|-
| style="font-style: italic;" | OCP and prothrombin G20210A
| style="font-style: italic;" |
| style="font-style: italic;" | 16
|-
| style="font-style: italic;" | OCP and protein C/S, or antithrombin III deficiency
| style="font-style: italic;" |
| style="font-style: italic;" | 9.7
|-
| Pregnancy
|
| 7
|-
| style="font-style: italic;" | Pregnancy and factor V leiden heterozygous
| style="font-style: italic;" |
| style="font-style: italic;" | 35
|-
| Cancer
|
| 5
|-
| History of venous thrombosis
|
| 50
|}
Data were extracted from multiple sources<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>.
 
==Prognosis==
*Certain thrombophilic conditions are high risk and require consideration for lifelong anticoagulation. In these cases, expert consultation is recommended.
 
{| class="wikitable"
! style="font-weight: bold;" | Possible indications for lifelong/prophylactic anticoagulation
|-
| 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==
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{{reflist|2}}
{{WH}}
{{WS}}
[[Category:Disease]]
[[Category:Hematology]]


[[Category:Hematology]]


{{WH}}
[[Category:Needs content]]
{{WS}}

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Asiri Ediriwickrema, M.D., M.H.S. [2]

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.
  • 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[1][2], 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[3][4][5].
  • The incidence of inherited thrombophilia in incident venous thrombosis is approximately 150-840 per 100,000 person years[6].
  • The incidence of inherited thrombophilia in recurrent venous thrombosis is approximately 3,500-10,500 per 100,000 person-years[6].

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[7].
  • 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[8].
  • 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[8].

Race

  • The factor V leiden G1691A and prothrombin G20210A mutations are exceedingly rare in non-white populations[2].

Epidemiology and Demographics

Prevalence of select inherited thrombophilias among whites

Inherited thrombophilia Healthy subjects/General population (%) Patients with recurrent thrombosis (%)
Factor V Leiden 1 - 20 18 - 50
Prothrombin G20210A 2 - 8 7 - 20
Antithrombin deficiency 0.02-2 1 - 5
Dysfibrinogenemia <1 <1
Protein C deficiency 0.2 - 5 3 - 10
Protein S deficiency 0.3 - 3 2 - 10
Hyperhomocystenemia <5 <10
Elevated factor VIII levels 11 25
  • 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%.

This data were consolidated from multiple sources[2][6][9][10][11]

References

  1. ↑ Stevens SM, Woller SC, Bauer KA, Kasthuri R, Cushman M, Streiff M; et al. (2016). "Guidance for the evaluation and treatment of hereditary and acquired thrombophilia". J Thromb Thrombolysis. 41 (1): 154–64. doi:10.1007/s11239-015-1316-1. PMC 4715840. PMID 26780744.
  2. ↑ 2.0 2.1 2.2 Seligsohn U, Lubetsky A (2001). "Genetic susceptibility to venous thrombosis". N Engl J Med. 344 (16): 1222–31. doi:10.1056/NEJM200104193441607. PMID 11309638.
  3. ↑ Margaglione M, Brancaccio V, Giuliani N, D'Andrea G, Cappucci G, Iannaccone L; et al. (1998). "Increased risk for venous thrombosis in carriers of the prothrombin G-->A20210 gene variant". Ann Intern Med. 129 (2): 89–93. PMID 9669991.
  4. ↑ Ridker PM, Hennekens CH, Lindpaintner K, Stampfer MJ, Eisenberg PR, Miletich JP (1995). "Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke, and venous thrombosis in apparently healthy men". N Engl J Med. 332 (14): 912–7. doi:10.1056/NEJM199504063321403. PMID 7877648.
  5. ↑ Koster T, Rosendaal FR, de Ronde H, Briët E, Vandenbroucke JP, Bertina RM (1993). "Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden Thrombophilia Study". Lancet. 342 (8886–8887): 1503–6. PMID 7902898.
  6. ↑ 6.0 6.1 6.2 Cohoon KP, Heit JA (2014). "Inherited and secondary thrombophilia". Circulation. 129 (2): 254–7. doi:10.1161/CIRCULATIONAHA.113.001943. PMC 3979345. PMID 24421360.
  7. ↑ White RH (2003). "The epidemiology of venous thromboembolism". Circulation. 107 (23 Suppl 1): I4–8. doi:10.1161/01.CIR.0000078468.11849.66. PMID 12814979.
  8. ↑ 8.0 8.1 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
  9. ↑ Buchanan GS, Rodgers GM, Ware Branch D (2003). "The inherited thrombophilias: genetics, epidemiology, and laboratory evaluation". Best Pract Res Clin Obstet Gynaecol. 17 (3): 397–411. PMID 12787534. Unknown parameter |month= ignored (help)
  10. ↑ Franco RF, Reitsma PH (2001). "Genetic risk factors of venous thrombosis". Hum. Genet. 109 (4): 369–84. doi:10.1007/s004390100593. PMID 11702218. Unknown parameter |month= ignored (help)
  11. ↑ Haverkate F, Samama M (1995). "Familial dysfibrinogenemia and thrombophilia. Report on a study of the SSC Subcommittee on Fibrinogen". Thromb. Haemost. 73 (1): 151–61. PMID 7740487. Unknown parameter |month= ignored (help)

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