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Thromb Haemost 1999; 82(02): 620-625
DOI: 10.1055/s-0037-1615888
Research Article
Schattauer GmbH

Thromboembolism and Pregnancy

Jeffrey S. Ginsberg
1   From the Department of Medicine, McMaster University, Hamilton, Ontario, CANADA
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Publication History

Publication Date:
09 December 2017 (online)

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Introduction

Antithrombotic therapy during pregnancy is used for the treatment and prophylaxis of venous thromboembolic disease, for the prevention and treatment of arterial embolism associated with valvular heart disease and/or prosthetic heart valves, for the prevention of fetal growth retardation and pregnancy loss in patients with antiphospholipid antibodies, and in patients with pregnancy-induced hypertension. Since antithrombotic agents have the potential to produce complications in both the mother and fetus, their use during pregnancy raises concerns. Guidelines are difficult to establish because the evidence upon which recommendations are based is derived primarily from poor-quality studies. This chapter reviews the fetal and maternal effects of antithrombotic agents including oral anticoagulants, unfractionated heparin, low molecular weight heparins (LMWH), and aspirin, and provides recommendations for their use during pregnancy.

 

  • References

  • 1 Svensson PJ, Dahlback B. Resistance to activated protein C as a basis for venous thrombosis. N Engl J Med 1994; 330: 517-522.
    CrossrefPubMedSearch in Google Scholar
  • 2 Dahlback B. Inherited thrombophilia: resistance to activated protein C as a pathogenic factor of venous thromboembolism. Blood 1995; 85: 607-614.
    PubMedSearch in Google Scholar
  • 3 Conard J, Horellou MH, Van Dreden P, Lecompte T, Samama M. Thrombosis and pregnancy in congenital deficiencies in AT III, protein C or protein S: study of 78 women. Thromb Haemost 1990; 63: 319-320.
    Thieme ConnectPubMedSearch in Google Scholar
  • 4 Long AA, Ginsberg JS, Brill-Edwards P, Johnston M, Turner C, Denburg JA, Bensen WG, Cividino A, Andrew M, Hirsh J. The relationship of antiphospholipid antibodies to thromboembolic disease in systemic lupus erythematosus: a cross-sectional study. Thromb Haemost 1991; 66: 520-524.
    Thieme ConnectPubMedSearch in Google Scholar
  • 5 de Swiet M, Floyd E, Letsky E. Low risk of recurrent thromboembolism in pregnancy. Br J Hosp Med 1987; 38: 264.
    PubMedSearch in Google Scholar
  • 6 Howell R, Fidler J, Letsky E, de Swiet M. The risks of antenatal subcutaneous heparin prophylaxis: a controlled trial. Br J Obstet Gynaecol 1983; 90: 1124-1128.
    CrossrefPubMedSearch in Google Scholar
  • 7 Badaracco MA, Vessey MP. Recurrence of venous thromboembolic disease and use of oral contraceptives. Br Med J 1974; 1: 215-217.
    CrossrefPubMedSearch in Google Scholar
  • 8 Tengborn L, Bergqvist D, Matzsch T, Bergqvist A, Hedner U. Recurrent thromboembolism in pregnancy and puerperium. Is there a need for thromboprophylaxis?. Am J Obstet Gynecol 1989; 160: 90-94.
    CrossrefPubMedSearch in Google Scholar
  • 9 Flessa HC, Kapstrom AB, Glueck HI, Will JJ. Placental transport of heparin. Am J Obstet Gynecol 1965; 93: 570-573.
    CrossrefPubMedSearch in Google Scholar
  • 10 Ginsberg JS, Hirsh J, Turner DC, Levine MN, Burrows R. Risks to the fetus of anticoagulant therapy during pregnancy. Thromb Haemost 1989; 61: 197-203.
    Thieme ConnectPubMedSearch in Google Scholar
  • 11 Ginsberg JS, Kowalchuk G, Hirsh J, Brill-Edwards P, Burrows R. Heparin therapy during pregnancy. Risks to the fetus and mother. Arch Intern Med 1989; 149: 2233-2236.
    CrossrefPubMedSearch in Google Scholar
  • 12 Hall JG, Pauli RM, Wilson KM. Maternal and fetal sequelae of anticoagulation during pregnancy. Am J Med 1980; 68: 122-140.
    CrossrefPubMedSearch in Google Scholar
  • 13 Becker MH, Genieser NB, Finegold M, Miranda D, Spackman T. Chondrodysplasis punctata:is maternal warfarin therapy a factor?. Am J Dis Child 1975; 129: 356-359.
    CrossrefPubMedSearch in Google Scholar
  • 14 Iturbe-Alessio I, Fonseca MC, Mutchinik O, Santos MA, Zajarias A, Salazar E. Risks of anticoagulant therapy in pregnant women with artificial heart valves. N Engl J Med 1986; 315: 1390-1393.
    CrossrefPubMedSearch in Google Scholar
  • 15 Hull R, Delmore T, Carter C, Hirsh J, Genton E, Gent M, Turpie G, McLaughlin D. Adjusted subcutaneous heparin versus warfarin sodium in the long-term treatment of venous thrombosis. N Engl J Med 1982; 306: 189-194.
    CrossrefPubMedSearch in Google Scholar
  • 16 Hull R, Hirsh J, Jay R, Carter C, England C, Gent M, Turpie AG, McLoughlin D, Dodd P, Thomas M, Raskob G, Ockelford P. Different intensities of oral anticoagulant therapy in the treatment of proximal-vein thrombosis. N Engl J Med 1982; 307: 1676-1681.
    CrossrefPubMedSearch in Google Scholar
  • 17 Anderson DR, Ginsberg JS, Burrows R, Brill-Edwards P. Subcutaneous heparin therapy during pregnancy: a need for concern at the time of delivery. Thromb Haemost 1991; 65: 248-250.
    Thieme ConnectPubMedSearch in Google Scholar
  • 18 Ginsberg JS, Kowalchuk G, Hirsh J, Brill-Edwards P, Burrows R, Coates G, Webber C. Heparin effect on bone density. Thromb Haemost 1990; 64: 286-289.
    Thieme ConnectPubMedSearch in Google Scholar
  • 19 Dahlman T, Lindvall N, Hellgren M. Osteopenia in pregnancy during long-term heparin treatment: a radiological study post partum. Br J Obstet Gynaecol 1990; 97: 221-228.
    CrossrefPubMedSearch in Google Scholar
  • 20 Barbour LA, Kick SD, Steiner JF, LoVerde ME, Heddleston LN, Lear JL, Baron AE, Barton PL. A prospective study of heparin-induced osteoporosis in pregnancy using bone densitometry. Am J Obstet Gynecol 1994; 170: 862-869.
    CrossrefPubMedSearch in Google Scholar
  • 21 Dahlman TC. Osteoporotic fractures and the recurrence of thromboembolism during pregnancy and the puerperium in 184 women undergoing thromboprophylaxis with heparin. Am J Obstet Gynecol 1993; 168: 1265-1270.
    CrossrefPubMedSearch in Google Scholar
  • 22 Douketis JD, Ginsberg JS, Burrows RF, Duku EK, Webber CE, Brill-Edwards P. The effects of long-term heparin therapy during pregnancy on bone density. A prospective matched cohort study. Thromb Haemost 1996; 75: 254-257.
    Thieme ConnectPubMedSearch in Google Scholar
  • 23 Anderson DR, Ginsberg JS, Brill-Edwards P, Demers C, Burrows RF, Hirsh J. The use of an indwelling Teflon catheter for subcutaneous heparin administration during pregnancy. A randomized crossover study. Arch Intern Med 1993; 153: 841-844.
    CrossrefPubMedSearch in Google Scholar
  • 24 O’Reilly R.. Anticoagulant, antithrombotic and thrombolytic drugs. In: Gilman AG, et al. eds. The pharmacologic basis of therapeutics. New York, NY: MacMillan; 1980: 1347-1366.
    Search in Google Scholar
  • 25 Orme ML, Lewis PJ, de Swiet M, Serlin MJ, Sibeon R, Baty JD, Breckenridge AM. May mothers given warfarin breast-feed their infants?. Br Med J 1977; 1: 1564-1565.
    CrossrefPubMedSearch in Google Scholar
  • 26 McKenna R, Cole ER, Vasan U. Is warfarin sodium contraindicated in the lactating mother?. J Pediatr 1983; 103: 325-327.
    CrossrefPubMedSearch in Google Scholar
  • 27 Gillis S, Shushan A, Eldor A. Use of low molecular weight heparin for prophylaxis and treatment of thromboembolism in pregnancy, Int. J Gynaecol Obstet 1992; 39: 297-301.
    PubMedSearch in Google Scholar
  • 28 Melissari E, Parker CJ, Wilson NV, Monte G, Kanthou C, Pemberton KD, Nicolaides KH, Barrett JJ, Kakkar VV. Use of low molecular weight heparin in pregnancy. Thromb Haemost 1992; 68: 652-656.
    Thieme ConnectPubMedSearch in Google Scholar
  • 29 Nelson-Piercy C, Letsky EA, de Swiet M. Low-molecular-weight heparin for obstetric thromboprophylaxis: experience of sixty-nine pregnancies in sixty-one women at high risk. Am J Obstet Gynecol 1997; 176: 1062-1068.
    CrossrefPubMedSearch in Google Scholar
  • 30 Hull RD, Raskob GE, Pineo GF, Green D, Trowbridge AA, Elliott CG, Lerner RG, Hall J, Sparling T, Brettell HR. et al Subcutaneous low-molecular-weight heparin compared with continuous intravenous heparin in the treatment of proximal-vein thrombosis. N Engl J Med 1992; 326: 975-982.
    CrossrefPubMedSearch in Google Scholar
  • 31 Prandoni P, Lensing AW, Buller HR, Carta M, Cogo A, Vigo M, Casara D, Ruol A, ten Cate JW. Comparison of subcutaneous low-molecular-weight heparin with intravenous standard heparin in proximal deep-vein thrombosis. Lancet 1992; 339: 441-445.
    CrossrefPubMedSearch in Google Scholar
  • 32 Nurmohamed MT, Rosendaal FR, Buller HR, Dekker E, Hommes DW, Vandenbroucke JP, Briet E. Low-molecular-weight heparin versus standard heparin in general and orthopaedic surgery: a meta-analysis. Lancet 1992; 340: 152-156.
    CrossrefPubMedSearch in Google Scholar
  • 33 Monreal M, Lafoz E, Olive A, del Rio L, Vedia C. Comparison of subcutaneous unfractionated heparin with a low molecular weight heparin (Fragmin) in patients with venous thromboembolism and contraindications to coumarin. Thromb Haemost 1994; 71: 7-11.
    Thieme ConnectPubMedSearch in Google Scholar
  • 34 Lensing AW, Prins MH, Davidson BL, Hirsh J. Treatment of deep venous thrombosis with low-molecular-weight heparins. A meta-analysis. Arch Intern Med 1995; 155: 601-607.
    CrossrefPubMedSearch in Google Scholar
  • 35 Siragusa S, Cosmi B, Piovella F, Hirsh H, Ginsberg JS. Low-molecular-weight heparins and unfractionated heparin in the treatment of patients with acute venous thromboembolism: results of a meta-analysis. Am J Med 1996; 100: 269-277.
    CrossrefPubMedSearch in Google Scholar
  • 36 Dolovich L, Ginsberg JS. Low-molecular-weight heparin in the treatment of venous thromboembolism: an updated meta-analysis. Vessels 1997; 3: 4-11.
    PubMedSearch in Google Scholar
  • 37 Forestier F, Daffos F, Capella-Pavlovsky M. Low molecular weight heparin (PK 10169) does not cross the placenta during the second trimester of pregnancystudy (according to PubMed) by direct fetal blood sampling under ultrasound. Thromb Res 1984; 34: 557-560.
    CrossrefPubMedSearch in Google Scholar
  • 38 Forestier F, Daffos F, Rainaut M, Toulemonde F. Low molecular weight heparin (CY 216) does not cross the placenta during the third trimester of pregnancy. Thromb Haemost 1987; 57: 234.
    Thieme ConnectPubMedSearch in Google Scholar
  • 39 Omri A, Delaloye JF, Andersen H, Bachmann F. Low molecular weight heparin does not cross the placenta during the second trimester of pregnancy. Thromb Haemost 1989; 61: 55-56.
    Thieme ConnectPubMedSearch in Google Scholar
  • 40 Shaughnessy SG, Young E, Deschamps P, Hirsh J. The effects of low molecular weight and standard heparin on calcium loss from fetal rat calvaria. Blood 1995; 86: 1368-1373.
    CrossrefPubMedSearch in Google Scholar
  • 41 Warkentin TE, Levine MN, Hirsh J, Horsewood P, Roberts RS, Gent M, Kelton JG. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med 1995; 332: 1330-1335.
    CrossrefPubMedSearch in Google Scholar
  • 42 Magnani HN. Heparin-induced thrombocytopenia (HIT): an overview of 230 patients treated with orgaran. Thromb Haemost 1993; 70: 554-561.
    Thieme ConnectPubMedSearch in Google Scholar
  • 43 Douketis JD, Kearon C, Bates S, Duku EK, Ginsberg JS. Risk of fatal pulmonary embolism in patients with treated venous thromboembolism. JAMA 1998; 279: 458-462.
    CrossrefPubMedSearch in Google Scholar
  • 44 Sbarouni E, Oakley CM. Outcome of pregnancy in women with valve prostheses. Br Heart J 1994; 71: 196-201.
    CrossrefPubMedSearch in Google Scholar
  • 45 Hirsh J. Heparin. N Engl J Med 1991; 324: 1565-1574.
    CrossrefPubMedSearch in Google Scholar
  • 46 Brill-Edwards P, Ginsberg JS, Johnston M, Hirsh J. Establishing a therapeutic range for heparin therapy. Ann Intern Med 1993; 119: 104-109.
    CrossrefPubMedSearch in Google Scholar
  • 47 Turpie AG, Gent M, Laupacis A, Latour Y, Gunstensen J, Basile F, Klimek M, Hirsh J. A comparison of aspirin with placebo in patients treated with warfarin after heart-valve replacement. N Engl J Med 1993; 329: 524-529.
    CrossrefPubMedSearch in Google Scholar
  • 48 Love PE, Santoro SA. Antiphospholipid antibodies: anticardiolipin and the lupus anticoagulant in systemic lupus erythematosus (SLE) and in non-SLE disorders. Prevalence and clinical significance. Ann Intern Med 1990; 112: 682-698.
    CrossrefPubMedSearch in Google Scholar
  • 49 Ginsberg JS, Brill-Edwards P, Johnston M, Denburg JA, Andrew M, Burrows RF, Bensen W, Cividino A, Long AA. Relationship of antiphospholipid antibodies to pregnancy loss in patients with systemic lupus erythematosus: a cross-sectional study. Blood 1992; 80: 975-980.
    PubMedSearch in Google Scholar