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Thromb Haemost 2003; 90(01): 77-85
DOI: 10.1055/s-0037-1613602
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Effect of hemostatic risk factors on the individual probability of thrombosis during pregnancy and the puerperium

Andrea Gerhardt
1   Department of Hemostasis and Transfusion Medicine, Heinrich Heine University Medical Center, Dusseldorf, Germany
,
Rüdiger E. Scharf
1   Department of Hemostasis and Transfusion Medicine, Heinrich Heine University Medical Center, Dusseldorf, Germany
,
Rainer B. Zotz
1   Department of Hemostasis and Transfusion Medicine, Heinrich Heine University Medical Center, Dusseldorf, Germany
› Author AffiliationsFinancial support: Supported by an institutional grant (# 9772153) of the Faculty of Medicine, Heinrich Heine University, Dusseldorf, Germany
Further Information

Publication History

Received 20 February 2003

Accepted after revision 08 April 2003

Publication Date:
07 December 2017 (online)

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Summary

In a retrospective study of 190 women with a first history of venous thromboembolism during pregnancy and the puerperium and 190 age-matched women with at least one prior pregnancy and no history of venous thromboembolism, the individual probability of thrombosis was determined. Assuming an overall risk of 1 in 1500 pregnancies, the probability of pregnancy-related thrombosis in carriers of homozygous factor V Leiden was 1 in 80 (odds ratio 20.6, p=0.005) and among carriers of combined heterozygous factor V Leiden and heterozygous G20210A mutation in the prothrombin gene 1 in 20 (odds ratio 88, p<0.001). The probability of thrombosis per pregnancy among women with elevated levels of factor VIII:C (>172 % activity) was 1 in 385 (odds ratio 4.5, p<0.001) and among those with increased levels of von Willebrand factor antigen (>190 %) 1 in 435 (odds ratio 4.0, p=0.002), independent of elevated factor VIII:C levels. The high prevalence of combined and homozygous defects of hemostatic components (21.6%) in patients as compared with normal women (0.86%) supports the concept that venous thromboembolism is a multicausal disorder.

Keywords

Pregnancy - venous thrombosis - risk factors - pulmonary embolism
 

  • References

  • 1 Prevention of venous thrombosis and pulmonary embolism. NIH Consensus Development. JAMA 1986; 256: 744-9.
    CrossrefPubMedGoogle Scholar
  • 2 Kierkegaard A. Incidence and diagnosis of deep vein thrombosis associated with pregnancy. Acta Obstetr Gynecol Scand 1983; 62: 239-43.
    CrossrefPubMedGoogle Scholar
  • 3 Treffers PE, Huidekoper BL, Weenink G. et al. Epidemiological observations of thromboembolic disease during pregnancy and in the puerperium, in 56,022 women. Int J Gynaecol Obstet 1983; 21: 327-31.
    CrossrefPubMedGoogle Scholar
  • 4 Rutherford S, Montoro M, Mc Gehee W. et al. Thromboembolic disease associated with pregnancy: an 11-year review. Am J Obste Gynecol 1991; 164 Suppl 186 abstract.
    PubMedGoogle Scholar
  • 5 Greer IA. Epidemiology, risk factors and prophylaxis of venous thromboembolism in obstetric and gynaecology. Clin Obstet Gynaecol 1997; 11: 403-30.
    PubMedGoogle Scholar
  • 6 Greer IA. Thrombosis in pregnancy: maternal and fetal issues. Lancet 1999; 353: 1258-65.
    CrossrefPubMedGoogle Scholar
  • 7 Monreal M, Lafoz E, Olive A. et al. Comparison of subcutaneous unfractionated heparin with a low molecular heparin (Fragmin) in patients with venous thromboembolism and con-traindications to coumarin. Thromb Haemost 1994; 717: 7-11.
    PubMedGoogle Scholar
  • 8 Sanson BJ, Lensing AWA, Prins HM. et al. Safety of low-molecular-weight heparin in pregnancy: a systematic review. Thromb Haemost 1999; 81: 668-72.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Zotz RB, Gerhardt A, Scharf RE. Prothrombin and factor V mutations in women with a history of thrombosis during pregnancy and the puerperium (Correspondence). N Engl J Med 2000; 342: 1996-7.
    CrossrefPubMedGoogle Scholar
  • 10 Brill-Edwards P, Ginsberg JS, Gent M. et al. Safety of withholding heparin in pregnant women with a history of venous thromboembolism. N Engl J Med 2000; 343: 439-44.
    CrossrefPubMedGoogle Scholar
  • 11 Mc Coll MD, Ellison J, Greer IA. et al. Prevalence of the post-thrombotic syndrome in young women with previous venous thromboembolism. Br J Haematol 2000; 108 (02) 272-4.
    CrossrefPubMedGoogle Scholar
  • 12 Rosendaal FR. Venous thrombosis: a multi-causal disease. Lancet 1999; 353: 1453-7.
    CrossrefPubMedGoogle Scholar
  • 13 Walker ID. Thrombophilia in pregnancy. J Clin Pathol 2000; 53: 573-80.
    CrossrefPubMedGoogle Scholar
  • 14 Greer IA. The challenge of thrombophilia in maternal-fetal medicine.. N Engl J Med 2000; 342: 424-5.
    CrossrefPubMedGoogle Scholar
  • 15 Hellgren M, Svensson PJ, Dahlbäck B. Resistance to activated protein C as a basis for venous thromboembolism associated with pregnancy and oral contraceptives. Am J Obstet Gynecol 1995; 173: 210-3.
    CrossrefPubMedGoogle Scholar
  • 16 Hallak M, Senderowicz J, Cassel A. et al. Activated protein R resistence (factor V Leid-en) associated with thrombosis in pregnancy. Am J Obstet Gynecol 1997; 176: 889-93.
    CrossrefPubMedGoogle Scholar
  • 17 Bokarewa MI, Bremme K, Blombäck M. Arg506-Gln mutation in factor V and risk of thrombosis during pregnancy. Br J Haematol 1996; 92: 473-8.
    CrossrefPubMedGoogle Scholar
  • 18 Mc Coll MD, Ramsey JE, Tait RC. et al. Risk factors for pregnancy associated venous thromboembolism. Thromb Haemost 1997; 78: 1183-8.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 Grandone E, Margaglione M, Colaizzo D. et al. Genetic susceptibility to pregnancy-related venous thromboembolism: Roles of factor V-Leiden, prothrombin G20210A, and methylentetrahydrofolat reductase C677T mutations. Am J Obstet Gynecol 1998; 179: 1324-8.
    CrossrefPubMedGoogle Scholar
  • 20 Gerhardt A, Scharf RE, Beckmann MW. et al. Prothrombin and factor V mutations in women with a history of thrombosis during pregnancy and the puerperium. N Engl J Med 2000; 342: 374-80.
    CrossrefPubMedGoogle Scholar
  • 21 McColl J, Ellison F, Reid RC. et al. Prothrom-bin 20210G-A, MTHFR C677T mutations in women with venous thromboembolism associated with pregnancy. Br J Obstet Gynaecol 2000; 107: 565-9.
    CrossrefPubMedGoogle Scholar
  • 22 Martinelli I, De Stefano V, Taioli E. et al. Inherited thrombophilia and first venous thromboembolism during pregnancy and puerperium. Thromb Haemost 2002; 87: 791-5.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 23 Pabinger I, Nemes L, Rintelen C. et al. Pregnancy-associated risk for venous thrombo-embolism and pregnancy outcome in women homozygous for factor V Leiden. Hematol J 2000; 1: 37-41.
    CrossrefPubMedGoogle Scholar
  • 24 Middeldorp S, Libourel EJ, Hamulyak K. et al. The risk of pregnancy-related venous thromboembolism in women who are homozygous for factor V Leiden. Br J Haemotol 2001; 113: 553-5.
    CrossrefPubMedGoogle Scholar
  • 25 Conard J, Horellou MH, van Dreden P. et al. Thrombosis in pregnancy and congenital deficiencies in ATIII, protein C or protein S: study of 78 women. Thromb Haemost 1990; 63: 319-20.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 26 De Stefano V, Leone G, Mastrangelo S. et al. Thrombosis during pregnancy and surgery in patients with congenital deficiency of anti-thrombin, protein C, protein S. Thromb Hae-most 1994; 71: 799-800. Letter
    Article in Thieme ConnectPubMedGoogle Scholar
  • 27 Pabinger I, Schneider B. The study group on natural inhibitors. Thrombotic risk in hereditary antithrombin, protein C or protein S deficiency. Arter Thromb Vasc Biol 1996; 16: 742-8.
    CrossrefPubMedGoogle Scholar
  • 28 Friederich P, Sanson BJ, Simioni P. et al. Frequency of pregnancy related venous thromboembolism in anticoagulant factor-deficient women: implications for prophylaxis. Ann Int Med 1996; 125: 955-60.
    CrossrefPubMedGoogle Scholar
  • 29 Seligsohn U, Lubetsky A. Genetic susceptibility to venous thrombosis. N Engl J Med 2001; 344: 1222-31.
    CrossrefPubMedGoogle Scholar
  • 30 Kearon C, Julian JA, Newman TE. et al. Noninvasive diagnosis of deep venous thrombosis. Ann Intern Med 1998; 128 (08) 663-77.
    CrossrefPubMedGoogle Scholar
  • 31 Bates SM, Ginsberg JS. How we manage venous thromboembolism during pregnancy. Blood 2002; 100 (10) 3470-8.
    CrossrefPubMedGoogle Scholar
  • 32 Pillny M, Sandmann W, Luther B. et al. Deep venous thrombosis during pregnancy and after delivery: Indications for and results of thrombectomy. J Vasc Surg 2003; 37: 528-32.
    CrossrefPubMedGoogle Scholar
  • 33 Frezzato M, Tosetto A, Rodeghiero F. Validated questionnaire for the identification of previous personal or familial venous thromboembolism. Am J Epidemol 1996; 143: 1257-65.
    CrossrefPubMedGoogle Scholar
  • 34 Ridker PM, Hennekens CH, Lindpaintner K. et al. 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 1995; 332: 912-7.
    CrossrefPubMedGoogle Scholar
  • 35 Poort SR, Rosendaal FR, Reitsma PH. et al. A common genetic variation in the 3 untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and increase in venous thrombosis. Blood 1996; 88: 3698-3703.
    PubMedGoogle Scholar
  • 36 Frosst P, Blom HJ, Milos R. et al. A candidate genetic risk factor for vascular disease in me-thylenetetrahydrofolate-reductase. Nat Genet 1995; 10: 111-3.
    CrossrefPubMedGoogle Scholar
  • 37 Rosendaal FR, Koster T, Vandenbroucke JP. et al. High risk of thrombosis in patients homozygous for factor V Leiden (activated protein C resistance). Blood 1995; 85: 1504-8.
    PubMedGoogle Scholar
  • 38 Emmerich J, Rosendaal FR, Cattaneo M. et al. Combined effect of factor V Leiden and Prothrombin 20210A on the risk of venous thromboembolism. Thromb Haemost 2001; 86: 809-16.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 39 Koster T, Blann AD, Briet E. et al. Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep-vein thrombosis. Lancet 1995; 345: 152-5.
    CrossrefPubMedGoogle Scholar
  • 40 O’Donnell J, Tuddenham EGD, Manning R. et al. High prevalence of elevated factor VIII levels in patients referred for thrombophilia screening: role of increased synthesis and relationship to the acute phase reaction. Thromb Haemost 1997; 77: 825-8.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 41 Kraaijenhagen RA, in’t Anker PS, Koopman MMW. et al. High plasma concentration of factor VIII:C is a major risk factor for venous thromboembolism. Thromb Haemost 2000; 83: 5-9.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 42 O’Donnell J, Mumford AD, Manning RA. et al. Elevation of FVIII:C in venous thromboembolism is persistent and independent of the acute phase response. Thromb Haemost 2000; 83: 10-3.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 43 Tait RC, Walker ID, Perry DJ. et al. Prevalence of antithrombin deficiency in the healthy population. Br J Haematol 1994; 87: 106-12.
    CrossrefPubMedGoogle Scholar