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Semin Thromb Hemost 2003; 29(2): 143-154
DOI: 10.1055/s-2003-38829
Copyright © 2003 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Prediction, Prevention, and Treatment of Venous Thromboembolic Disease in Pregnancy

Rainer B. Zotz1 , Andrea Gerhardt2 , Rüdiger E. Scharf2
  • 1Department of Hemostasis and Transfusion Medicine, Heinrich Heine University Medical Center, Düsseldorf, Germany
  • 2Department of Hemostasis and Transfusion Medicine, Heinrich Heine University Medical Center, Düsseldorf, Germany
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Publikationsdatum:
23. April 2003 (online)

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ABSTRACT

Pregnancy is recognized as an independent risk factor for venous thromboembolism leading to thromboembolic events, particularly in women with prior venous thrombosis, family history of thrombosis, or additional thrombophilic risk factors. To reduce the incidence of venous thromboembolism in pregnancy and improve outcomes, an individual risk stratification on the basis of probability of thrombosis as a rationale for an individual risk-adapted prophylaxis is required. In women without prior thrombosis, the presence of a heterozygous factor V Leiden or heterozygous G20210A mutation in the prothrombin gene is associated with a pregnancy-associated thrombotic risk of approximately 1 in 400. Thus, in pregnant carriers of either one of these mutations the risk of venous thromboembolism is low. For this reason, routine thrombophilia screening of all pregnant women is not recommended. However, a combination of the two genetic risk factors can increase the risk to a modest level (risk 1 in 25). In women with a single episode of prior thrombosis associated with a transient risk factor (such as surgery or trauma) and no additional genetic risk factor, the probability of a pregnancy-associated thrombosis also appears to be low. In contrast, in women with a prior idiopathic venous thrombosis who carry an additional hereditary risk factor or who have a positive family history of thrombosis, a high risk (> 10%) can be expected, supporting the indication for active antepartum and postpartum heparin prophylaxis. In many cases, the absolute magnitude of risk is unknown or estimated, and recommendations are often empiric.

KEYWORDS

Pregnancy - venous thrombosis - risk factors - therapy - prevention

REFERENCES

  • 1 National Institutes of Health Consensus Development Conference. Prevention of venous thrombosis and pulmonary embolism.  JAMA . 1986;  256 744-749
    CrossrefPubMedSuche in Google Scholar
  • 2 Kierkegaard A. Incidence and diagnosis of deep vein thrombosis associated with pregnancy.  Acta Obstet Gynaecol Scand . 1983;  62 239-243
    PubMedSuche in Google Scholar
  • 3 Treffers P E, Huidekoper B L, Weenink G, Kloosterman G. Epidemiological observations of thromboembolic disease during pregnancy and in the puerperium, in 56,022 women.  Int J Gynaecol Obstet . 1983;  21 327-331
    CrossrefPubMedSuche in Google Scholar
  • 4 Rutherford S, Montoro M, Mc Gehee W, Strong T. Thromboembolic disease associated with pregnancy: an 11-year review (Abst).  Am J Obstet Gynecol . 1991;  164(Suppl) 186
    PubMedSuche in Google Scholar
  • 5 Greer I A. Epidemiology, risk factors and prophylaxis of venous thromboembolism in obstetrics and gynaecology.  Clin Obstet Gynaecol . 1997;  11 403-430
    PubMedSuche in Google Scholar
  • 6 Greer I A. Thrombosis in pregnancy: maternal and fetal issues.  Lancet . 1999;  353 1258-1265
    CrossrefPubMedSuche in Google Scholar
  • 7 Mc Coll M, Walker I, Greer I A. The role of inherited thrombophilia in venous thromboembolism associated with pregnancy.  Br J Obstet Gynaecol . 1999;  106 756-766
    PubMedSuche in Google Scholar
  • 8 Greer I A. The challenge of thrombophilia in maternal-fetal medicine.  N Engl J Med . 2000;  342 424-425
    CrossrefPubMedSuche in Google Scholar
  • 9 Seligsohn U, Lubetsky A. Genetic susceptibility to venous thrombosis.  N Engl J Med . 2001;  344 1222-1231
    CrossrefPubMedSuche in Google Scholar
  • 10 Rosendaal F R. Venous thrombosis: a multicausal disease.  Lancet . 1999;  353 1453-1457
    CrossrefPubMedSuche in Google Scholar
  • 11 Mansvelt E PG, Laffan M, McVey J H, Tuddenham E GD. Analysis of the F8 gene in individuals with high plasma factor VIII:C levels and associated venous thrombosis.  Thromb Haemost . 1998;  80 561-565
    PubMedSuche in Google Scholar
  • 12 Virchow R. Phlogose und Thrombose im Gefäßsystem. In: Gesammelte Abhandlungen zur Wissenschaftlichen Medizin Frankfurt: Staatsdruckerei; 1856
    Suche in Google Scholar
  • 13 Greer I A. Haemostasis and thrombosis in pregnancy. In: Bloom AL, Forbes CD, Thomas DP, Tuddenham EGD, eds. Haemostasis and Thrombosis London: Churchill Livingstone 1994: 987-1015
    Suche in Google Scholar
  • 14 Walker I D. Thrombophilia in pregnancy.  J Clin Pathol . 2000;  53 573-580
    CrossrefPubMedSuche in Google Scholar
  • 15 Macklon N S, Greer I A, Bowman A W. An ultrasound study of gestational and postural changes in the deep venous system of the leg in pregnancy.  Br J Obstet Gynaecol . 1997;  104 191-197
    PubMedSuche in Google Scholar
  • 16 Ginsberg J S, Brill-Edwards P, Burrows R F. et al . DVT during pregnancy: leg and trimester of presentation.  Thromb Haemost . 1992;  67 519-520
    PubMedSuche in Google Scholar
  • 17 Cockett F B, Thomas M L, Negus D. Iliac vein compression: its relation to iliofemoral thrombosis and the post-thrombotic syndrome.  BMJ . 1967;  2 214-219
    PubMedSuche in Google Scholar
  • 18 Ginsberg J S, Greer I A, Hirsh J. Use of antithrombotic agents during pregnancy.  Chest . 2001;  119 122S-131S
    CrossrefPubMedSuche in Google Scholar
  • 19 Conard J, Horellou M H, van Dreden P, le Compte T, Samama M. Thrombosis in pregnancy and congenital deficiencies in ATIII, protein C or protein S: study of 78 women.  Thromb Haemost . 1990;  63 319-320
    PubMedSuche in Google Scholar
  • 20 De Stefano V, Leone G, Mastrangelo S. et al . Thrombosis during pregnancy and surgery in patients with congenital deficiency of antithrombin, protein C, protein S (Letter).  Thromb Haemost . 1994;  71 799-800
    PubMedSuche in Google Scholar
  • 21 Pabinger I, Schneider B, and the Study Group on Natural Inhibitors. Thrombotic risk in hereditary antithrombin, protein C or protein S deficiency.  Arterioscl Thromb Vasc Biol . 1996;  16 742-748
    CrossrefPubMedSuche in Google Scholar
  • 22 Friederich P, Sanson B J, Simioni P. et al . Frequency of pregnancy related venous thromboembolism in anticoagulant factor-deficient women: implications for prophylaxis.  Ann Intern Med . 1996;  125 955-960
    CrossrefPubMedSuche in Google Scholar
  • 23 Gerhardt A, Scharf R E, Beckmann M W. et al . Prothrombin and factor V mutations in women with a history of thrombosis during pregnancy and the puerperium.  N Engl J Med . 2000;  342 374-380
    CrossrefPubMedSuche in Google Scholar
  • 24 Dahlbäck B, Carlsson M, Svensson P J. Familial thrombophilia due to a previously unrecognised mechanism characterized by poor anticoagulant response to activated protein C.  Proc Natl Acad Sci USA . 1993;  90 1004-1008
    CrossrefPubMedSuche in Google Scholar
  • 25 Bertina R M, Koeleman P C, Köster T. et al . Mutation in blood coagulation factor V associated with resistance to activated protein C.  Nature . 1994;  369 64-66
    CrossrefPubMedSuche in Google Scholar
  • 26 Rees D C, Cox M, Clegg J B. World distribution of factor V Leiden.  Lancet . 1995;  346 1133-1134
    CrossrefPubMedSuche in Google Scholar
  • 27 Köster T, Rosendaal F R, Briet E. et al . Protein C deficiency in a controlled series of unselected outpatients: an infrequent but clear risk factor for venous thrombosis (Leiden Thrombophilia Study).  Blood . 1995;  85 2756-2761
    PubMedSuche in Google Scholar
  • 28 van den Belt G M A, Prins M H, Huisman M H, Hirsh J. Familial thrombophilia: a review analysis.  Clin Appl Thromb Hemost . 1996;  2 227-236
    PubMedSuche in Google Scholar
  • 29 Rosendaal F R, Köster T, Vandenbroucke J P, Reitsma P H. High risk of thrombosis in patients homozygous for factor V Leiden (activated protein C resistance).  Blood . 1995;  85 1504-1508
    PubMedSuche in Google Scholar
  • 30 Emmerich J, Rosendaal F R, Cattaneo M. et al . Combined effect of factor V Leiden and Prothrombin 20210A on the risk of venous thromboembolism.  Thromb Haemost . 2001;  86 809-816
    Thieme ConnectPubMedSuche in Google Scholar
  • 31 Hellgren M, Svensson P J, Dahlbäck B. Resistance to activated protein C as a basis for venous thromboembolism associated with pregnancy and oral contraceptives.  Am J Obstet Gynecol . 1995;  173 210-213
    CrossrefPubMedSuche in Google Scholar
  • 32 Hallak M, Senderowicz J, Cassel A. et al . Activated protein C resistance (factor V Leiden) associated with thrombosis in pregnancy.  Am J Obstet Gynecol . 1997;  176 889-893
    PubMedSuche in Google Scholar
  • 33 Bokarewa M I, Bremme K, Blombäck M. Arg506-Gln mutation in factor V and risk of thrombosis during pregnancy.  Br J Haematol . 1996;  92 473-478
    CrossrefPubMedSuche in Google Scholar
  • 34 Mc Coll D M, Ramsey J E, Tait R C. et al . Risk factors for pregnancy associated venous thromboembolism.  Thromb Haemost . 1997;  78 1183-1188
    PubMedSuche in Google Scholar
  • 35 Grandone E, Margaglione M, Colaizzo D. et al . Genetic susceptibility to pregnancy-related venous thromboembolism: roles of factor V- Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations.  Am J Obstet Gynecol . 1998;  179 1324-1328
    CrossrefPubMedSuche in Google Scholar
  • 36 McColl M D, Ellison J, Reid F. et al . Prothrombin 20210G-A, MTHFR C677T mutations in women with venous thromboembolism associated with pregnancy.  Br J Obstet Gynaecol . 2000;  107 565-569
    PubMedSuche in Google Scholar
  • 37 Poort S R, Rosendaal F R, Reitsma P H, Bertina R M. A common genetic variation in the &3acute; untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and increase in venous thrombosis.  Blood . 1996;  88 3698-3703
    CrossrefPubMedSuche in Google Scholar
  • 38 Rosendaal F R, Doggen C JM, Zivelin A. et al . Geographic distribution of the 20210 G to A prothrombin variant.  Thromb Haemost . 1998;  79 706-708
    Thieme ConnectPubMedSuche in Google Scholar
  • 39 Martinelli I, Sacchi E, Landi G. et al . High risk of cerebral-vein thrombosis in carriers of a prothrombin-gene mutation and in users of oral contraceptives.  N Engl J Med . 1998;  338 1793-1797
    CrossrefPubMedSuche in Google Scholar
  • 40 Ghavari A E, Pierangeli S S. Origin of antiphospholipid antibodies: induction of aPL by viral peptides.  Lupus . 1998;  7 52-54
    PubMedSuche in Google Scholar
  • 41 Ghavari A E, Sammaritano L R, Wen J. et al . Characteristics of human immunodeficiency virus and chlorpromazine induced antiphospholipid antibodies: effect of beta 2 glycoprotein I on binding to phospholipid.  J Rheumatol . 1994;  21 94-99
    PubMedSuche in Google Scholar
  • 42 Love P E, Santoro S A. Antiphospholipid antibodies: anticardiolipin and the lupus anticoagulant in systemic lupus erythematodes (SLE) and non SLE disorders.  Ann Intern Med . 1990;  112 682-698
    CrossrefPubMedSuche in Google Scholar
  • 43 Long A A, Ginsberg J S, Brill-Edwards P. et al . The relationship of antiphospholipid antibodies to thromboembolic disease in systemic lupus erythematodes: a cross sectional study.  Thromb Haemost . 1991;  66 520-524
    PubMedSuche in Google Scholar
  • 44 Ginsberg J S, Brill-Edwards P, Johnston M. et al . Relationship of antiphospholipid antibodies to pregnancy loss in patients with systemic lupus erythematodes: a cross sectional study.  Blood . 1992;  80 975-980
    PubMedSuche in Google Scholar
  • 45 Levine J S, Branch D W, Rauch J. The antiphospholipid syndrome.  N Engl J Med . 2002;  346 752-763
    CrossrefPubMedSuche in Google Scholar
  • 46 Ginsberg J S, Wells P S, Brill-Edwards P. et al . Antiphospholipid antibodies and venous thromboembolism.  Blood . 1995;  86 3685-3691
    CrossrefPubMedSuche in Google Scholar
  • 47 Simioni P, Prandoni P, Zanon E. et al . Deep venous thrombosis and lupus anticoagulant.  Thromb Haemost . 1996;  76 187-189
    PubMedSuche in Google Scholar
  • 48 Mateo J, Oliver A, Borrell M, Sala N, Fontcuberta J. Laboratory evaluation and clinical characterisation of 2132 consecutive unselected patients with venous thromboembolism-results of the Spanish multicentre study on thrombophilia (EMET-study).  Thromb Haemost . 1997;  77 444-451
    PubMedSuche in Google Scholar
  • 49 Kamashta M A, Cuadrado M J, Mujic F. et al . The management of thrombosis in the antiphospholipid syndrome.  N Engl J Med . 1995;  332 993-997
    CrossrefPubMedSuche in Google Scholar
  • 50 Brill-Edwards P, Ginsberg J S, Gent M. et al . Safety of withholding heparin in pregnant women with a history of venous thromboembolism.  N Engl J Med . 2000;  343 1439-1444
    CrossrefPubMedSuche in Google Scholar
  • 51 Zotz R B, Gerhardt A, Scharf R E. Prothrombin and factor V mutations in women with a history of thrombosis during pregnancy and the puerperium (Letter).  N Engl J Med . 2000;  342 1996-1997
    CrossrefPubMedSuche in Google Scholar
  • 52 Flessa H C, Klapstrom A B, Glueck M J, Will J J. Placental transport of heparin.  Am J Obstet Gynecol . 1965;  93 570-573
    CrossrefPubMedSuche in Google Scholar
  • 53 Blombäck M, Bremme K, Hellgren M, Lindberg H. A pharmacokinetic study of dalteparin during late pregnancy.  Blood Coagul Fibrinolysis . 1998;  9 343-350
    PubMedSuche in Google Scholar
  • 54 Forestier F, Daffos F, Capella-Pavlovsky M. Low molecular weight heparin (PK 10169) does not cross the placenta during the second trimester of pregnancy: study by direct fetal blood sampling under ultrasound.  Thromb Res . 1984;  34 557-560
    CrossrefPubMedSuche in Google Scholar
  • 55 O'Reilly R. Anticoagulant, antithrombotic and thrombolytic drugs. In: Gillmann AG, Goodman LS, eds. The Pharmacologic Basis of Therapeutics, 6th ed New York: Macmillan 1980: 1347
    Suche in Google Scholar
  • 56 Warkentin T E, Levine M N, Hirsh J. et al . Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin.  N Engl J Med . 1995;  332 1330-1335
    CrossrefPubMedSuche in Google Scholar
  • 57 Sanson B J, Lensing A WA, Prins H M. et al . Safety of low-molecular-weight heparin in pregnancy: a systematic review.  Thromb Haemost . 1999;  81 668-672
    PubMedSuche in Google Scholar
  • 58 Douketis J D, Ginsberg J S, Burrows R F. et al . The effects of long-term heparin therapy during pregnancy on bone density. A prospective matched cohort study.  Thromb Haemost . 1996;  75 254-257
    PubMedSuche in Google Scholar
  • 59 Pettilä V, Kaaja R, Leinonen P. et al . Thromboprophylaxis with low molecular weight heparin (dalteparin) in pregnancy.  Thromb Res . 1999;  96 275-282
    CrossrefPubMedSuche in Google Scholar
  • 60 Bates S M, Ginsberg J S. Anticoagulants in pregnancy: fetal defects. In: Greer IA, ed. Bailliere's Clinical Obstetrics and Gynaecology-Thromboembolic Disease in Obstetrics and Gynaecology London: Bailliere Tindall 1997: 479-488
    Suche in Google Scholar
  • 61 Elkayam U. Pregnancy through a prosthetic heart valve.  J Am Coll Cardiol . 1999;  33 1642-1645
    CrossrefPubMedSuche in Google Scholar
  • 62 Chan W S, Anand S, Ginsberg J S. Anticoagulation of pregnant women with mechanical heart valves: a systematic review of the literature.  Arch Intern Med . 2000;  160 191-196
    CrossrefPubMedSuche in Google Scholar
  • 63 Tait R C, Walker I D, Perry D J. et al . Prevalence of antithrombin deficiency in the healthy population.  Br J Haematol . 1994;  87 106-112
    CrossrefPubMedSuche in Google Scholar
  • 64 Tait R C, Walker I D, Reitsma P H. et al . Prevalence of protein C deficiency in the healthy population.  Thromb Haemost . 1995;  73 87-93
    PubMedSuche in Google Scholar