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Prevalence and thrombosis risk for selected thrombophilias

Prevalence and thrombosis risk for selected thrombophilias
Thrombophilia Prevalence Relative risk (absolute annualized risk) of initial VTE* Relative risk of recurrent VTE Relative risk (absolute annualized risk) of initial VTE, OCP users* Relative risk (absolute annualized risk) of initial VTE, HRT users*Δ Absolute risk of VTE in pregnancy*
FVL heterozygous 2 to 7% 3.48 to 5.51 (0.05 to 0.2%) 1.1 to 1.8 2.47 to 15.04 (0.1 to 0.6%) 1.4 to 13.16 (1.6 to 5.97%) 0.5% at age <35,
0.7% at age ≥35
FVL homozygous 0.06 to 0.25% 6.79 to 19.29 (0.8%) 1.8 Uncertain Uncertain 2.2% at age <35,
3.4% at age ≥35
PGM heterozygous 1 to 2% 2.25 to 3.48 (0.13%) 0.7 to 2.3 3.60 to 8.63 (2.85%) 0.4% at age <35,
0.6% at age ≥35
PGM homozygous Rare 2.19 to 20.72 Uncertain Uncertain Uncertain Not available
Compound FVL and PGM heterozygosity 0.1% 1.13 to 5.04 (0.42%) 2.7 3.79 to 76.47 (0.17%) Uncertain 5.5% at age <35,
8.2% at age ≥35
PC deficiency 0.2 to 0.5% 10 (0.4 to 2.3%) 1.8 1.7 to 23.9 (1.7 to 7.1%) (2.96%) 0.7% at age <35,
1.1% at age ≥35
PS deficiency 0.1 to 0.7% 9.6 (0.7 to 3.2%) 1.0 1.4 to 17.1 (1.3 to 2.4%) (2.3%) 0.7% at age <35,
1.0% at age ≥35
AT deficiency 0.02% 10 to 30 (1.2 to 4.4%) 2.6 1.4 to 115.8 (2.5 to 5.1%) (5.73%) 6.1% at age <35,
9.0% at age ≥35
APS 2% 7 1.5 to 6.8 0.3 to 3.1 (1.05 to 2.63%) 15.8
Individuals with the following thrombophilias are considered at high risk for VTE: AT deficiency, homozygotes for FVL, homozygotes for prothrombin G20210A (PGM), and double heterozygotes for FVL and PGM.

VTE: venous thromboembolism; OCP: oral contraceptive pill (containing estrogen); HRT: hormone replacement therapy (containing estrogen); FVL: factor V Leiden; PGM: prothrombin gene G20210A mutation; PC: protein C; PS: protein S; AT: antithrombin; APS: antiphospholipid syndrome.

* Data are taken from reference 14; therefore, absolute rates may differ from the other sources since calculations are based on prevalence and relative risk.[1-13]

¶ Relative risks are compared with nonusers without thrombophilia.

Δ With the exception of heterozygous FVL, estimates are based on modeling rather than epidemiologic studies.
References:
  1. Christiansen SC, Cannegieter SC, Koster T, et al. Thrombophilia, clinical factors, and recurrent venous thrombotic events. JAMA 2005; 293:2352.
  2. Dalen JE. Should patients with venous thromboembolism be screened for thrombophilia? Am J Med 2008; 121:458.
  3. Simone B, De Stefano V, Leoncini E, et al. Risk of venous thromboembolism associated with single and combined effects of factor V Leiden, prothrombin 20210A and methylenetethraydrofolate reductase C677T: a meta-analysis involving over 11,000 cases and 21,000 controls. Eur J Epidemiol 2013; 28:621.
  4. Mahmoodi BK, Brouwer JL, Ten Kate MK, et al. A prospective cohort study on the absolute risks of venous thromboembolism and predictive value of screening asymptomatic relatives of patients with hereditary deficiencies of protein S, protein C or antithrombin. J Thromb Haemost 2010; 8:1193.
  5. Pernod G, Biron-Andreani C, Morange PE, et al. Recommendations on testing for thrombophilia in venous thromboembolic disease: a French consensus guideline. J Mal Vasc 2009; 34:156.
  6. Merriman L, Greaves M. Testing for thrombophilia: an evidence-based approach. Postgrad Med J 2006; 82:699.
  7. Wu O, Robertson L, Twaddle S, et al. Screening for thrombophilia in high-risk situations: a meta-analysis and cost effectiveness analysis. Br J Haematol 2005; 131:80.
  8. Bates SM, Greer IA, Middeldorp S, et al. VTE, thrombophilia, antithrombotic therapy, and pregnancy. Chest 2012; 141:e691S.
  9. Lindhoff-Last E, Luxembourg B. Evidence-based indications for thrombophilia screening. Vasa 2008; 37:19.
  10. Cohen W, Castelli C, Suchon P, et al. Risk assessment of venous thrombosis in families with known hereditary thrombophilia: the MARseilles-NImes prediction model. J Thromb Haemost 2014; 12:138.
  11. Davis SM, Branch DW. Thromboprophylaxis in pregnancy: who and how? Obstet Gynecol Clin North Am 2010; 37:333.
  12. Culwell KR, Curtis KM, del Carmen Cravioto M. Safety of contraceptive method use among women with systemic lupus erythematosus: a systematic review. Obstet Gynecol 2009; 114:341.
  13. Wu O, Robertson L, Langhorne P, et al. Oral contraceptives, hormone replacement therapy, thrombophilias and risk of venous thromboembolism: a systematic review. The thrombosis: risk and Economic Assessment of Thrombophilia Screening (TREATS) Study. Thromb Haemost 2005; 94:17.
  14. Gerhardt A, Scharf RE, Greer IA, Zotz RB. Hereditary risk factors of thrombophilia and probability of venous thromboembolism during pregnancy and the puerperium. Blood 2016; 128:2343.

From: Stevens SM, Woller SC, Bauer KA, et al. Guidance for the evaluation and treatment of hereditary and acquired thrombophilia. J Thromb Thrombolysis 2016; 41:154. Available at: https://link.springer.com/article/10.1007%2Fs11239-015-1316-1. Copyright © 2016 Stevens SM, Woller SC, Bauer KA, et al. Reproduced under the terms of the Creative Commons Attribution License 4.0.

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