Skip to main content
SpringerLink
Log in

Anticoagulants and Antiplatelet Agents in Pregnancy

  • Chapter
Disorders of Thrombosis and Hemostasis in Pregnancy

Abstract

Management of anticoagulant or antiplatelet therapy in pregnant women is challenging because of a paucity of data on its efficacy and safety during pregnancy. Current recommendations are based largely on extrapolation of data from non-pregnant patients, and case reports and case series of pregnant women. The treating physician has to consider the potential complications for both mother and fetus, and the possible impact of the frequently altered pharmacokinetics and pharmacodynamics of anticoagulants during pregnancy. Decision making should also be informed by the values and preferences of the pregnant woman. Here we collate and discuss current information and consensus guidance on the safety and efficacy of anticoagulants and several antiplatelet agents during pregnancy and lactation, providing a tool to aid management.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Hirsh J. Heparin. N Engl J Med. 1991;324(22):1565–74.

    CAS  PubMed  Google Scholar 

  2. Windsor E, Freeman L. Investigation of routes of administration of heparin other than injection. Am J Med. 1964;37(3):408–16.

    CAS  PubMed  Google Scholar 

  3. Hull RD, Raskob GE, Hirsh J, Jay RM, Leclerc JR, Geerts WH, et al. Continuous intravenous heparin compared with intermittent subcutaneous heparin in the initial treatment of proximal vein thrombosis. N Engl J Med. 1986;315(18):1109–14.

    CAS  PubMed  Google Scholar 

  4. Pini M, Pattacini C, Quintavalla R, Poli T, Megha A, Tagliaferri A, et al. Subcutaneous vs intravenous heparin in the treatment of deep venous thrombosis—a randomized clinical-trial. Thromb Haemost. 1990;64(2):222–6.

    CAS  PubMed  Google Scholar 

  5. De Swart CAM, Nijmeyer B, Roelofs JMM, Sixma JJ. Kinetics of intravenously administered heparin in normal humans. Blood. 1982;60(6):1251–8.

    PubMed  Google Scholar 

  6. Garcia DA, Baglin T, Weitz JI, Samama MM, American College of Chest Physicians. Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e24S–43.

    CAS  PubMed Central  PubMed  Google Scholar 

  7. Glimelius B, Busch C, Hook M. Binding of heparin on surface of cultured human endothelial cells. Thromb Res. 1978;12(5):773–82.

    CAS  PubMed  Google Scholar 

  8. Mahadoo J, Hiebert L, Jaques LB. Vascular sequestration of heparin. Thromb Res. 1978;12(1):79–90.

    CAS  PubMed  Google Scholar 

  9. Bjornsson TD, Wolfram KM, Kitchell BB. Heparin kinetics determined by 3 assay-methods. Clin Pharmacol Ther. 1982;31(1):104–13.

    CAS  PubMed  Google Scholar 

  10. Flessa HC, Kapstrom AB, Glueck HI, Will JJ. Placental transport of heparin. Am J Obstet Gynecol. 1965;93(4):570–3.

    CAS  PubMed  Google Scholar 

  11. Schneider D, Heilmann L, Harenberg J. Placental transfer of low-molecular heparin. Geburtshilfe Frauenheilkd. 1995;55(2):93–8.

    CAS  PubMed  Google Scholar 

  12. Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO, American College of Chest Physicians. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e691S–736.

    CAS  PubMed Central  PubMed  Google Scholar 

  13. Ginsberg JS, Kowalchuk G, Hirsh J, Brilledwards P, Burrows R. Heparin-therapy during pregnancy—risks to the fetus and mother. Arch Intern Med. 1989;149(10):2233–6.

    CAS  PubMed  Google Scholar 

  14. Royal College of Obstetricians and Gynaecologists. Reducing the risk of venous thromboembolism during pregnancy and the puerperium, Green-top guideline no 37a. London RCOG; 2015. https://www.rcog.org.uk/guidelines.

  15. Briggs GG, Freeman RK, Yaffee SJ. Drugs in pregnancy and lactation: a reference guide to fetal and neonatal risk. 9th ed. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins; 2011.

    Google Scholar 

  16. Weitz JI. Low-molecular-weight heparins. N Engl J Med. 1997;337(10):688–98.

    CAS  PubMed  Google Scholar 

  17. Handeland GF, Abildgaard U, Holm HA, Arnesen KE. Dose adjusted heparin treatment of deep venous thrombosis—a comparison of unfractionated and low-molecular-weight heparin. Eur J Clin Pharmacol. 1990;39(2):107–12.

    CAS  PubMed  Google Scholar 

  18. Harenberg J. Pharmacology of low-molecular-weight heparins. Semin Thromb Hemost. 1990;16(Suppl):12–8.

    PubMed  Google Scholar 

  19. Bara L, Samama M. Pharmacokinetics of low-molecular-weight heparins. Acta Chir Scand Suppl. 1988;543:65–72.

    Google Scholar 

  20. Pfizer. Summary of product characteristics: Fragmin (dalteparin) 10,000 units/ml—treatment of VTE. The electronic medicines compendium. 2013. https://www.medicines.org.uk/emc/.

  21. Dunn CJ, Jarvis B. Dalteparin—an update of its pharmacological properties and clinical efficacy in the prophylaxis and treatment of thromboembolic disease. Drugs. 2000;60(1):203–37.

    CAS  PubMed  Google Scholar 

  22. Sanofi-Aventis. Summary of product characteristics: Clexane (enoxaparin) pre-filled syringes and Clexane multidose vial. The electronic medicines Compendium. 2014. https://www.medicines.org.uk/emc/.

  23. Siddiqui MAA, Wagstaff AJ. Enoxaparin—a review of its use as thromboprophylaxis in acutely ill, nonsurgical patients. Drugs. 2005;65(7):1025–36.

    CAS  PubMed  Google Scholar 

  24. Leo-Laboratories. Summary of product characteristics: Innohep (tinzaparin) 20,000 IU/ml and InnohepSyringe 20,000 IU/ml. The electronic medicines compendium. 2015. https://www.medicines.org.uk/emc/.

  25. Cheer SM, Dunn CJ, Foster R. Tinzaparin sodium—a review of its pharmacology and clinical use in the prophylaxis and treatment of thromboembolic disease. Drugs. 2004;64(13):1479–502.

    CAS  PubMed  Google Scholar 

  26. Samama MM, Gerotziafas GT. Comparative pharmacokinetics of LMWHs. Semin Thromb Hemost. 2000;26:31–8.

    CAS  PubMed  Google Scholar 

  27. Boneu B, Caranobe C, Sie P. Pharmacokinetics of heparin and low-molecular-weight heparin. Baillieres Clin Haematol. 1990;3(3):531–44.

    Google Scholar 

  28. Davison JM, Noble MCB. Serial changes in 24-hour creatinine clearance during normal menstrual cycles and the first trimester of pregnancy. Br J Obstet Gynaecol. 1981;88(1):10–7.

    CAS  PubMed  Google Scholar 

  29. Anderson GD. Pregnancy-induced changes in pharmacokinetics—a mechanistic-based approach. Clin Pharmacokinet. 2005;44(10):989–1008.

    CAS  PubMed  Google Scholar 

  30. Paaby P, Nielsen A, Mollerpetersen J, Raffn K. Cyclical changes in endogenous overnight creatinine clearance during the 3rd trimester of pregnancy. Acta Med Scand. 1988;223(5):459–68.

    CAS  PubMed  Google Scholar 

  31. Casele HL, Laifer SA, Woelkers DA, Venkataramanan R. Changes in the pharmacokinetics of the low-molecular-weight heparin enoxaparin sodium during pregnancy. Am J Obstet Gynecol. 1999;181(5):1113–7.

    CAS  PubMed  Google Scholar 

  32. Blomback M, Bremme K, Hellgren M, Lindberg H. A pharmacokinetic study of dalteparin (Fragmin (R)) during late pregnancy. Blood Coagul Fibrinolysis. 1998;9(4):343–50.

    CAS  PubMed  Google Scholar 

  33. Lebaudy C, Hulot JS, Amoura Z, Costedoat-Chalumeau N, Serreau R, Ankri A, et al. Changes in enoxaparin pharmacokinetics during pregnancy and implications for antithrombotic therapeutic strategy. Clin Pharmacol Ther. 2008;84(3):370–7.

    CAS  PubMed  Google Scholar 

  34. Rodie VA, Thomson AJ, Stewart FM, Quinn AJ, Walker ID, Greer IA. Low-molecular-weight heparin for the treatment of venous thromboembolism in pregnancy: a case series. BJOG. 2002;109(9): 1020–4.

    Google Scholar 

  35. Jacobsen AF, Qvigstad E, Sandset PM. Low-molecular-weight heparin (dalteparin) for the treatment of venous thromboembolism in pregnancy. BJOG. 2003;110(2):139–44.

    Google Scholar 

  36. Barbour LA, Oja JL, Schultz LK. A prospective trial that demonstrates that dalteparin requirements increase in pregnancy to maintain therapeutic levels of anticoagulation. Am J Obstet Gynecol. 2004;191(3):1024–9.

    CAS  PubMed  Google Scholar 

  37. Friedrich E, Hameed AB. Fluctuations in anti-factor Xa levels with therapeutic enoxaparin anticoagulation in pregnancy. J Perinatol. 2010;30(4):253–7.

    CAS  PubMed  Google Scholar 

  38. Kitchen S, Iampietro R, Woolley AM, Preston FE. Anti-Xa monitoring during treatment with low-molecular-weight heparin or danaparoid: inter-assay variability. Thromb Haemost. 1999;82(4):1289–93.

    Google Scholar 

  39. Baglin T, Barrowcliffe TW, Cohen A, Greaves M, British Committee for Standards in Haematology. Guidelines on the use and monitoring of heparin. Br J Haematol. 2006;133(1):19–34.

    CAS  PubMed  Google Scholar 

  40. Levine MN, Planes A, Hirsh J, Goodyear M, Vochelle N, Gent M. The relationship between anti-factor Xa level and clinical outcome in patients receiving Enoxaparine low-molecular weight heparin to prevent deep-vein thrombosis after hip-replacement. Thromb Haemost. 1989;62(3):940–4.

    CAS  PubMed  Google Scholar 

  41. Greaves M. Limitations of the laboratory monitoring of heparin therapy. Thromb Haemost. 2002;87(1): 163–4.

    CAS  PubMed  Google Scholar 

  42. Dolovich LR, Ginsberg JS, Douketis JD, Holbrook AM, Cheah G. A meta-analysis comparing low-molecular-weight heparins with unfractionated heparin in the treatment of venous thromboembolism—examining some unanswered questions regarding location of treatment, product type, and dosing frequency. Arch Intern Med. 2000;160(2):181–8.

    CAS  PubMed  Google Scholar 

  43. Gould MK, Dembitzer AD, Doyle RL, Hastie TJ, Garber AM. Low-molecular-weight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis—a meta-analysis of randomized, controlled trials. Ann Intern Med. 1999;130(10):800–9.

    CAS  PubMed  Google Scholar 

  44. Nurmohamed MT, Rosendaal FR, Buller HR, Dekker E, Hommes DW, Vandenbroucke JP, et al. Low-molecular-weight heparin versus standard heparin in general and orthopedic surgery—a metaanalysis. Lancet. 1992;340(8812):152–6.

    CAS  PubMed  Google Scholar 

  45. Lopaciuk S, Bielska-Falda H, Noszczyk W, Bielawiec M, Witkiewicz W, Filipecki S, et al. Low-molecular-weight heparin versus acenocoumarol in the secondary prophylaxis of deep vein thrombosis. Thromb Haemost. 1999;81(1):26–31.

    Google Scholar 

  46. van der Heijden JF, Prins MH, Buller HR. Low-molecular-weight heparins: are they interchangeable? Haemostasis. 2000;30:148–57.

    PubMed  Google Scholar 

  47. Pini M, Aiello S, Manotti C, Pattacini C, Quintavalla R, Poli T, et al. Low-molecular-weight heparin versus warfarin in the prevention of recurrence after deep vein thrombosis. Thromb Haemost. 1994;72(2):191–7.

    CAS  PubMed  Google Scholar 

  48. Greer IA, Nelson-Piercy C. Low-molecular-weight heparins for thromboprophylaxis and treatment of venous thromboembolism in pregnancy: a systematic review of safety and efficacy. Blood. 2005;106(2):401–7.

    CAS  PubMed  Google Scholar 

  49. Waterstone M, Bewley S, Wolfe C. Incidence and predictors of severe obstetric morbidity: case-control study. Br Med J. 2001;322(7294):1089–93.

    CAS  Google Scholar 

  50. Forestier F, Daffos F, Capellapavlovsky M. Low-molecular-weight heparin (PK-10169) does not cross the placenta during the 2nd trimester of pregnancy by direct fetal blood-sampling under ultrasound. Thromb Res. 1984;34(6):557–60.

    Google Scholar 

  51. Forestier F, Daffos F, Rainaut M, Toulemonde F. Low-molecular-weight heparin (CY216) does not cross the placenta during third trimester of pregnancy. Thromb Haemost. 1987;57(2):234.

    Google Scholar 

  52. Robertson AF. Reflections on errors in neonatology III. The “experienced” years, 1970 to 2000. J Perinatol. 2003;23:240–49.

    Google Scholar 

  53. Richter C, Sitzmann J, Lang P, Weitzel H, Huch A, Huch R. Excretion of low-molecular-weight heparin in human milk. Br J Clin Pharmacol. 2001;52(6): 708–10.

    Google Scholar 

  54. GlaxoSmithKline. Summary of product characteristics: Arixtra (fondaparinux) 2.5mg, 5mg, 7.5mg, 10mg solution for injection, pre-filled syringe. The electronic medicines Compendium. 2013. 12 June 2011.

    Google Scholar 

  55. Samama MM, Gerotziafas GT. Evaluation of the pharmacological properties, and clinical results of the synthetic pentasaccharide (fondaparinux). Thromb Res. 2003;109(1):1–11.

    CAS  PubMed  Google Scholar 

  56. Lagrange F, Vergnes C, Brun JL, Paolucci F, Nadal T, Leng JJ, et al. Absence of placental transfer of pentasaccharide (Fondaparinux, Arixtra) in the dually perfused human cotyledon in vitro. Thromb Haemost. 2002;87(5):831–5.

    CAS  PubMed  Google Scholar 

  57. Dempfle CEH. Minor transplacental passage of fondaparinux in vivo. N Engl J Med. 2004;350(18):1914–5.

    CAS  PubMed  Google Scholar 

  58. Winger E, Reed J. Fondaparinux versus enoxaparin treatment in women with infertility or pregnancy loss. Haematologica. 2009;95:0455.

    Google Scholar 

  59. Knol HM, Schultinge L, Erwich J, Meijer K. Fondaparinux as an alternative anticoagulant therapy during pregnancy. J Thromb Haemost. 2010;8(8):1876–9.

    CAS  PubMed  Google Scholar 

  60. Linkins LA, Dans AL, Moores LK, Bona R, Davidson BL, Schulman S, Crowther M, American College of Chest Physicians. Treatment and prevention of heparin-induced thrombocytopenia: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e495S–530.

    CAS  PubMed Central  PubMed  Google Scholar 

  61. Rauova L, Poncz M, McKenzie SE, Reilly MP, Arepally G, Weisel JW, et al. Ultralarge complexes of PF4 and heparin are central to the pathogenesis of heparin-induced thrombocytopenia. Blood. 2005; 105(1):131–8.

    CAS  PubMed  Google Scholar 

  62. Horsewood P, Warkentin TE, Hayward CPM, Kelton JG. The epitope specificity of heparin-induced thrombocytopenia. Br J Haematol. 1996;95(1):161–7.

    CAS  PubMed  Google Scholar 

  63. Watson H, Davidson S, Keeling D. Guidelines on the diagnosis and management of heparin-induced thrombocytopenia: second edition. Br J Haematol. 2012;159(5):528–40.

    PubMed  Google Scholar 

  64. Martel N, Lee J, Wells PS. Risk for heparin-induced thrombocytopenia with unfractionated and low-molecular-weight heparin thromboprophylaxis: a meta-analysis. Blood. 2005;106(8):2710–5.

    CAS  PubMed  Google Scholar 

  65. Kalkwarf HJ, Specker BL. Bone mineral changes during pregnancy and lactation. Endocrine. 2002; 17(1):49–53.

    CAS  PubMed  Google Scholar 

  66. Koo WW, Walters JC, Esterlitz J, Levine RJ, Bush AJ, Sibai B. Maternal calcium supplementation and fetal bone mineralization. Obstet Gynecol. 1999;94(4):577–82.

    CAS  PubMed  Google Scholar 

  67. Khastgir G, Studd J. Pregnancy-associated osteoporosis. Br J Obstet Gynaecol. 1994;101(10):836–8.

    CAS  PubMed  Google Scholar 

  68. Khovidhunkit W, Epstein S. Osteoporosis in pregnancy. Osteoporos Int. 1996;6(5):345–54. 2.

    CAS  PubMed  Google Scholar 

  69. Murphy MS, John PR, Mayer AD, Buckels JA, Kelly DA. Heparin therapy and bone fractures. Lancet. 1992;340(8827):1098.

    CAS  PubMed  Google Scholar 

  70. Rupp WM, McCarthy HB, Rohde TD, Blackshear PJ, Goldenberg FJ, Buchwald H. Risk of osteoporosis in patients treated with long-term intravenous heparin therapy. Curr Surg. 1982;39(6):419–22.

    CAS  PubMed  Google Scholar 

  71. Sackler JP, Liu L. Heparin-induced osteoporosis. Br J Radiol. 1973;46(547):548–50.

    CAS  PubMed  Google Scholar 

  72. Muir JM, Hirsh J, Weitz JI, Andrew M, Young E, Shaughnessy SG. A histomorphometric comparison of the effects of heparin and low-molecular-weight heparin on cancellous bone in rats. Blood. 1997;89(9):3236–42.

    CAS  PubMed  Google Scholar 

  73. Bhandari M, Hirsh J, Weitz JI, Young E, Venner TJ, Shaughnessy SG. The effects of standard and low-molecular-weight heparin on bone nodule formation in vitro. Thromb Haemost. 1998;80(3):413–7.

    Google Scholar 

  74. 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(4):1368–73.

    CAS  PubMed  Google Scholar 

  75. Rajgopal R, Bear M, Butcher MK, Shaughnessy SG. The effects of heparin and low-molecular-weight heparins on bone. Thromb Res. 2008;122(3):293–8.

    Google Scholar 

  76. Dahlman TC, Sjoberg HE, Ringertz H. Bone-mineral density during long-term prophylaxis with heparin in pregnancy. Am J Obstet Gynecol. 1994;170(5):1315–20.

    CAS  PubMed  Google Scholar 

  77. 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(2):254–7.

    CAS  PubMed  Google Scholar 

  78. 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(4):1265–70.

    CAS  PubMed  Google Scholar 

  79. Pettila V, Kaaja R, Leinonen P, Ekblad U, Kataja M, Ikkala E. Thromboprophylaxis with low-molecular-weight heparin (dalteparin) in pregnancy. Thromb Res. 1999;96(4):275–82.

    Google Scholar 

  80. 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(5):1062–8.

    CAS  PubMed  Google Scholar 

  81. Carlin AJ, Farquharson RG, Quenby SM, Topping J, Fraser WD. Prospective observational study of bone mineral density during pregnancy: low-molecular-weight heparin versus control. Hum Reprod. 2004;19(5):1211–4.

    Google Scholar 

  82. Le Templier G, Rodger MA. Heparin-induced osteoporosis and pregnancy. Curr Opin Pulm Med. 2008;14(5):403–7.

    PubMed  Google Scholar 

  83. Matziolis G, Perka C, Disch A, Zippel H. Effects of fondaparinux compared with dalteparin, enoxaparin and unfractionated heparin on human osteoblasts. Calcif Tissue Int. 2003;73(4):370–9.

    CAS  PubMed  Google Scholar 

  84. Handschin AE, Trentz OA, Hoerstrup SP, Kock HJ, Wanner GA, Trentz O. Effect of low-molecular-weight heparin (dalteparin) and fondaparinux (Arixtra) on human osteoblasts in vitro. Br J Surg. 2005;92(2):177–83.

    Google Scholar 

  85. Merck Sharp & Dohme. Summary of product characteristics: Orgaran (danaparoid). The electronic medicines compendium. 1998.

    Google Scholar 

  86. Wilde MI, Markham A. Danaparoid—a review of its pharmacology and clinical use in the management of heparin-induced thrombocytopenia. Drugs. 1997;54(6):903–24.

    CAS  PubMed  Google Scholar 

  87. Danhof M, Deboer A, Magnani HN, Stiekema JCJ. Pharmacokinetic considerations on Orgaran (ORG-10172) therapy. Haemostasis. 1992;22(2): 73–84.

    CAS  PubMed  Google Scholar 

  88. Farner B, Eichler P, Kroll H, Greinacher A. A comparison of danaparoid and lepirudin in heparin-induced thrombocytopenia. Thromb Haemost. 2001;85(6):950–7.

    CAS  PubMed  Google Scholar 

  89. Newman PM, Swanson RL, Chong BH. Heparin-induced thrombocytopenia: IgG binding to PF4-heparin complexes in the fluid phase and cross-reactivity with low-molecular-weight heparin and heparinoid. Thromb Haemost. 1998;80(2):292–7.

    Google Scholar 

  90. Keng TB, Chong BH. Heparin-induced thrombocytopenia and thrombosis syndrome: in vivo cross-reactivity with danaparoid and successful treatment with r-Hirudin. Br J Haematol. 2001;114(2):394–6.

    CAS  PubMed  Google Scholar 

  91. Peeters LLH, Hobbelen PMJ, Verkeste CM, Vogel GMT, Hasenack HG, Meuleman DG, et al. Placental transfer of Org-10172, a low-molecular-weight heparinoid, in the awake late pregnant guinea-pig. Thromb Res. 1986;44(3):277–83.

    CAS  PubMed  Google Scholar 

  92. Magnani HN. An analysis of clinical outcomes of 91 pregnancies in 83 women treated with danaparoid (Orgaran). Thromb Res. 2010;125(4):297–302.

    CAS  PubMed  Google Scholar 

  93. Chapman ML, Martinez-Borges AR, Mertz HL. Lepirudin for treatment of acute thrombosis during pregnancy. Obstet Gynecol. 2008;112(2):432–3.

    PubMed  Google Scholar 

  94. Furlan A, Vianello F, Clementi M, Prandoni P. Heparin- induced thrombocytopenia occurring in the first trimester of pregnancy: successful treatment with lepirudin. A case report. Haematologica. 2006;91(8 Suppl):ECR40.

    PubMed  Google Scholar 

  95. Harenberg J, Jorg I, Bayerl C, Fiehn C. Treatment of a woman with lupus pernio, thrombosis and cutaneous intolerance to heparins using lepirudin during pregnancy. Lupus. 2005;14(5):411–2.

    CAS  PubMed  Google Scholar 

  96. Mehta R, Golichowski A. Treatment of heparin induced thrombocytopenia and thrombosis during the first trimester of pregnancy. J Thromb Haemost. 2004;2(9):1665–6.

    CAS  PubMed  Google Scholar 

  97. Lindhoff-Last E, Bauersachs R. Heparin-induced thrombocytopenia—alternative anticoagulation in pregnancy and lactation. Semin Thromb Hemost. 2002;28(5):439–45.

    CAS  PubMed  Google Scholar 

  98. Markwardt F, Fink G, Kaiser B, Kloecking HP, Nowak G, Richter M, et al. Pharmacological survey of recombinant hirudin. Pharmazie. 1988;43(3):202–7.

    CAS  PubMed  Google Scholar 

  99. Bates SM, Greer IA, Pabinger I, Sofaer S, Hirsh J. Venous thromboembolism, thrombophilia, antithrombotic therapy, and pregnancy. Chest. 2008; 133(6):844S–86.

    CAS  PubMed  Google Scholar 

  100. Mitsubishi-Pharma-Europe. Summary of product characteristics Exembol (argatroban) 100mg/mL concentrate for solution for infusion. The electronic medicines compendium. 2014. https://www.medicines.org.uk/emc/.

  101. Ekbatani A, Asaro LR, Malinow AM. Anticoagulation with argatroban in a parturient with heparin-induced thrombocytopenia. Int J Obstet Anesth. 2010;19(1):82–7.

    CAS  PubMed  Google Scholar 

  102. Tanimura K, Ebina Y, Sonoyama A, Morita H, Miyata S, Yamada H. Argatroban therapy for heparin-induced thrombocytopenia during pregnancy in a woman with hereditary antithrombin deficiency. J Obstet Gynaecol Res. 2012;38(4):749–52.

    PubMed  Google Scholar 

  103. Young SK, Al-Mondhiry HA, Vaida SJ, Ambrose A, Botti JJ. Successful use of argatroban during the third trimester of pregnancy: case report and review of the literature. Pharmacotherapy. 2008;28(12): 1531–6.

    PubMed  Google Scholar 

  104. Hale TW. Medication and mother’s milk 2012: a manual of lactational pharmacology. 15th ed. Amarillo: Hale Publishing; 2012.

    Google Scholar 

  105. Wockhardt. Summary of product characteristics: Prosulf (protamine sulphate) 10mg/ml solution for injection. The electronic medicines compendium. 2010. https://www.medicines.org.uk/emc/.

  106. Hirsh J, Levine MN. Low-molecular-weight heparin. Blood. 1992;79(1):1–17.

    CAS  PubMed  Google Scholar 

  107. Majerus PW. Arachidonate metabolism in vascular disorders. J Clin Invest. 1983;72(5):1521–5.

    CAS  PubMed Central  PubMed  Google Scholar 

  108. Patrono C, Baigent C, Hirsh J, Roth G. Antiplatelet drugs. Chest. 2008;133(6):199S–233.

    CAS  PubMed  Google Scholar 

  109. Loll PJ, Picot D, Garavito RM. The structural basis of aspirin activity inferred from crystal structure of inactivated prostaglandin H-2 synthase. Nat Struct Biol. 1995;2(8):637–43.

    CAS  PubMed  Google Scholar 

  110. Roth GJ, Majerus PW. The mechanism of the effect of aspirin on human platelets. I. Acetylation of a particulate fraction protein. J Clin Invest. 1975;56(3):624–32.

    CAS  PubMed Central  PubMed  Google Scholar 

  111. Burch JW, Stanford N, Majerus PW. Inhibition of platelet prostaglandin synthetase by oral aspirin. J Clin Invest. 1978;61(2):314–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  112. Patrono C, Ciabattoni G, Patrignani P, Pugliese F, Filabozzi P, Catella F, et al. Clinical-pharmacology of platelet cyclooxygenase inhibition. Circulation. 1985;72(6):1177–84.

    CAS  PubMed  Google Scholar 

  113. Pedersen AK, Fitzgerald GA. Dose-related kinetics of aspirin—presystemic acetylation of platelet cyclooxygenase. N Engl J Med. 1984;311(19): 1206–11.

    CAS  PubMed  Google Scholar 

  114. Bhatt DL, Scheiman J, Abraham NS, Antman EM, Chan FKL, Furberg CD, American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents, et al. ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use. Am J Gastroenterol. 2008;103(11): 2890–907.

    CAS  PubMed  Google Scholar 

  115. de Abajo FJ, Garcia Rodriguez LA. Risk of upper gastrointestinal bleeding and perforation associated with low-dose aspirin as plain and enteric-coated formulations. BMC Clin Pharmacol. 2001;1:1.

    PubMed Central  PubMed  Google Scholar 

  116. Källén BA. Use of omeprazole during pregnancy—no hazard demonstrated in 955 infants exposed during pregnancy. Eur J Obstet Gynecol Reprod Biol. 2001;96(1):63–8.

    PubMed  Google Scholar 

  117. Diav-Citrin O, Arnon J, Shechtman S, Schaefer C, Tonningen MR, Clementi M, et al. The safety of proton pump inhibitors in pregnancy: a multicentre prospective controlled study. Aliment Pharmacol Ther. 2005;21(3):269–75.

    CAS  PubMed  Google Scholar 

  118. Plante L, Ferron GM, Unruh M, Mayer PR. Excretion of pantoprazole in human breast milk. J Reprod Med. 2004;49(10):825–7.

    PubMed  Google Scholar 

  119. Marshall JK, Thomson ABR, Armstrong D. Omeprazole for refractory gastroesophageal reflux disease during pregnancy and lactation. Can J Gastroenterol. 1998;12(3):225–7.

    CAS  PubMed  Google Scholar 

  120. Tulppala M, Viinikka L, Ylikorkala O. Thromboxane dominance and prostacyclin deficiency in habitual abortion. Lancet. 1991;337(8746):879–81.

    CAS  PubMed  Google Scholar 

  121. Ylikorkala O, Viinikka L. The role of prostaglandins in obstetrical disorders. Baillieres Clin Obstet Gynaecol. 1992;6(4):809–27.

    CAS  PubMed  Google Scholar 

  122. Kaaja R, Julkunen H, Viinikka L, Ylikorkala O. Production of prostacyclin and thromboxane in lupus pregnancies—effect of small dose of aspirin. Obstet Gynecol. 1993;81(3):327–31.

    CAS  PubMed  Google Scholar 

  123. Corby DG. Aspirin in pregnancy—maternal and fetal effects. Pediatrics. 1978;62(5):930–7.

    CAS  PubMed  Google Scholar 

  124. Slone D, Siskind V, Heinonen OP, Monson RR, Kaufman DW, Shapiro S. Aspirin and congenital-malformations. Lancet. 1976;1(7974):1373–5.

    CAS  PubMed  Google Scholar 

  125. Kozer E, Nikfar S, Costei A, Boskovic R, Nulman I, Koren G. Aspirin consumption during the first trimester of pregnancy and congenital anomalies: a meta-analysis. Am J Obstet Gynecol. 2002;187(6): 1623–30.

    PubMed  Google Scholar 

  126. Norgard B, Puho E, Czeizel AE, Skriver MV, Sorensen HT. Aspirin use during early pregnancy and the risk of congenital abnormalities: a population-based case-control study. Am J Obstet Gynecol. 2005;192(3):922–3.

    CAS  PubMed  Google Scholar 

  127. CLASP Collaborative Group. Low dose aspirin in pregnancy and early childhood development: follow up of the collaborative low dose aspirin study in pregnancy. CLASP collaborative group. Br J Obstet Gynaecol. 1995;102(11):861–8.

    Google Scholar 

  128. Palmisano P, Cassady G. Salicylate exposure in the perinate. JAMA. 1969;209(4):556–8.

    CAS  PubMed  Google Scholar 

  129. Levy G, Garretts LK. Kinetics of salicylate elimination by newborn-infants of mothers who ingested aspirin before delivery. Pediatrics. 1974;53(2): 201–10.

    CAS  PubMed  Google Scholar 

  130. Noschel H, Bonow A, Moller R, Estel C, Muller B. Placental passage of sodium salicylate. Zentralbl Gynakol. 1972;94(13):437–42.

    CAS  PubMed  Google Scholar 

  131. Benigni A, Gregorini G, Frusca T, Chiabrando C, Ballerini S, Valcamonico A, et al. Effect of low-dose aspirin on fetal and maternal generation of thromboxane by platelets in women at risk for pregnancy-induced hypertension. N Engl J Med. 1989;321(6): 357–62.

    CAS  PubMed  Google Scholar 

  132. Viinikka L, Hartikainensorri AL, Lumme R, Hiilesmaa V, Ylikorkala O. Low-dose aspirin in hypertensive pregnant-women—effect on pregnancy outcome and prostacyclin thromboxane balance in mother and newborn. Br J Obstet Gynaecol. 1993;100(9):809–15.

    CAS  PubMed  Google Scholar 

  133. Sibai BM, Caritis SN, Thom E, Shaw K, McNellis D. Low dose aspirin in nulliparous women—safety of continuous epidural block and correlation between bleeding time and maternal-neonatal bleeding complications. Am J Obstet Gynecol. 1995;172(5): 1553–7.

    CAS  PubMed  Google Scholar 

  134. Horlocker TT, Wedel DJ, Rowlingson JC, Enneking FK, Kopp SL, Benzon HT, et al. Regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy: American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines (Third Edition). Reg Anesth Pain Med. 2010;35(1):64–101.

    CAS  PubMed  Google Scholar 

  135. Gogarten W, Vandermeulen E, Van Aken H, Kozek S, Llau JV, Samama CM. Regional anaesthesia and antithrombotic agents: recommendations of the European Society of Anaesthesiology. Eur J Anaesthesiol. 2010;27(12):999–1015.

    CAS  PubMed  Google Scholar 

  136. Lewis RB, Schulman JD. Influence of acetylsalicylic acid, an inhibitor of prostaglandin synthesis, on duration of human gestation and labor. Lancet. 1973;2(7839):1159–61.

    CAS  PubMed  Google Scholar 

  137. Joint Formulary Committee. British National Formulary (BNF). 66th ed. London/Chicago: Pharmaceutical Press; 2013.

    Google Scholar 

  138. Kauffman RE, Banner W, Berlin CM, Blumer JL, Gorman RL, Lambert GH, et al. The transfer of drugs and other chemicals into human milk. Pediatrics. 1994;93(1):137–50.

    Google Scholar 

  139. Sweetman SC, editor. Martindale: the complete drug reference. 37th ed. London: Pharmaceutical Press; 2011.

    Google Scholar 

  140. Sanofi-Aventis. Summary of product characteristics: Plavix (clopidogrel) 75mg film-coated tablets. The electronic medicines Compendium. 2015. https://www.medicines.org.uk/emc/.

  141. De Santis M, De Luca C, Mappa I, Cesari E, Mazza A, Quattrocchi T, et al. Clopidogrel treatment during pregnancy: a case report and a review of literature. Intern Med. 2011;50(16):1769–73.

    PubMed  Google Scholar 

  142. Klinzing P, Markert UR, Liesaus K, Peiker G. Case report: successful pregnancy and delivery after myocardial infarction and essential thrombocythemia treated with clopidrogel. Clin Exp Obstet Gynecol. 2001;28(4):215–6.

    CAS  PubMed  Google Scholar 

  143. Santiago-Díaz P, Arrebola-Moreno AL, Ramírez-Hernández JA, Melgares-Moreno R. Platelet antiaggregants in pregnancy. Rev Esp Cardiol. 2009;62(10):1197–8 [Article in English, Spanish].

    PubMed  Google Scholar 

  144. Al-Aqeedi RF, Al-Nabti AD. Drug-eluting stent implantation for acute myocardial infarction during pregnancy with use of glycoprotein IIb/IIIa inhibitor, aspirin and clopidogrel. J Invasive Cardiol. 2008;20(5):E146–9.

    PubMed  Google Scholar 

  145. Shah P, Dzavik V, Cusimano RJ, Sermer M, Okun N, Ross J. Spontaneous dissection of the left main coronary artery. Can J Cardiol. 2004;20(8):815–8.

    PubMed  Google Scholar 

  146. Boehringer-Ingelheim. Summary of product characteristics Persantin (dipyridamol) 100mg tablets. The electronic medicines compendium. 2015.

    Google Scholar 

  147. Eikelboom JW, Hirsh J, Spencer FA, Baglin TP, Weitz JI. Antiplatelet drugs: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e89S–119.

    CAS  PubMed Central  PubMed  Google Scholar 

  148. Hall JG, Pauli RM, Wilson KM. Maternal and fetal sequelae of anticoagulation during pregnancy. Am J Med. 1980;68(1):122–40.

    CAS  PubMed  Google Scholar 

  149. Chan WS, Anand S, Ginsberg JS. Anticoagulation of pregnant women with mechanical heart valves—a systematic review of the literature. Arch Intern Med. 2000;160(2):191–6.

    CAS  PubMed  Google Scholar 

  150. Schaefer C, Hannemann D, Meister R, Elefant E, Paulus W, Vial T, et al. Vitamin K antagonists and pregnancy outcome—a multi-centre prospective study. Thromb Haemost. 2006;95(6):949–57.

    CAS  PubMed  Google Scholar 

  151. Vitale N, De Feo M, De Santo LS, Pollice A, Tedesco N, Cotrufo M. Dose-dependent fetal complications of warfarin in pregnant women with mechanical heart valves. J Am Coll Cardiol. 1999;33(6): 1637–41.

    CAS  PubMed  Google Scholar 

  152. Chong MB, Harvey D, Deswiet M. Follow-up-study of children whose mothers were treated with Warfarin during pregnancy. Br J Obstet Gynaecol. 1984;91(11):1070–3.

    CAS  PubMed  Google Scholar 

  153. Wesseling J, Van Driel D, Heymans HSA, Rosendaal FR, Geven-Boere LM, Smrkovsky M, et al. Coumarins during pregnancy: long-term effects on growth and development of school-age children. Thromb Haemost. 2001;85(4):609–13.

    CAS  PubMed  Google Scholar 

  154. Orme ML, Lewis PJ, Swiet MD, Serlin MJ, Sibeon R, Baty JD, et al. May mothers given warfarin breast feed their infants. Br Med J. 1977;1(6076):1564–5.

    CAS  PubMed Central  PubMed  Google Scholar 

  155. McKenna R, Cole ER, Vasan U. Is warfarin sodium contraindicated in the lactating mother. J Pediatr. 1983;103(2):325–7.

    CAS  PubMed  Google Scholar 

  156. Clark SL, Porter TF, West FG. Coumarin derivatives and breast-feeding. Obstet Gynecol. 2000;95(6): 938–40.

    CAS  PubMed  Google Scholar 

  157. Boehringer-Ingelheim. Summary of product characteristics Pradaxa 75mg, 110mg and 150mg hard capsules The electronic medicines compendium. 2013.

    Google Scholar 

  158. Eikelboom JW, Connolly SJ, Brueckmann M, Granger CB, Kappetein AP, Mack MJ, et al. RE-ALIGN Investigators. Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med. 2013;369(13):1206–14.

    Google Scholar 

  159. Eriksson BI, Quinla DJ, Weitz JI. Comparative pharmacodynamics and pharmacokinetics of oral direct thrombin and factor Xa inhibitors in development. Clin Pharmacokinet. 2009;48(1):1–22.

    CAS  PubMed  Google Scholar 

  160. Di Nisio M, Middeldorp S, Büller HR. Direct thrombin inhibitors. N Engl J Med. 2005;353(10): 1028–40.

    PubMed  Google Scholar 

  161. Baetz BE, Spinler SA. Dabigatran etexilate: an oral direct thrombin inhibitor for prophylaxis and treatment of thromboembolic diseases. Pharmacotherapy. 2008;28(11):1354–73.

    CAS  PubMed  Google Scholar 

  162. Eisert WG, Hauel N, Stangier J, Wienen W, Clemens A, van Ryn J. Dabigatran. An oral novel potent reversible nonpeptide inhibitor of thrombin. Arterioscler Thromb Vasc Biol. 2010;30(10):1885–9.

    CAS  PubMed  Google Scholar 

  163. Perzborn E, Strassburger J, Wilmen A, Pohlmann J, Roehrig S, Schlemmer KH, et al. In vitro and in vivo studies of the novel antithrombotic agent BAY 59-7939—an oral, direct Factor Xa inhibitor. J Thromb Haemost. 2005;3(3):514–21.

    CAS  PubMed  Google Scholar 

  164. Wong PC, Pinto DJP, Zhang D. Preclinical discovery of apixaban, a direct and orally bioavailable factor Xa inhibitor. J Thromb Thrombolysis. 2011;31(4):478–92.

    CAS  PubMed Central  PubMed  Google Scholar 

  165. Bayer. Summary of product characteristics Xarelto 10mg and 20mg film coated tablets. The electronic medicines compendium. 2013.

    Google Scholar 

  166. Bristol-Myers Squibb-Pfizer. Summary of product characteristics Eliquis (apixaban) 5mg film-coated tablets. The electronic medicines compendium. 2013.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free London NHS Foundation Trust, Pond Street, London, NW3 2QG, UK

    Anja B. Drebes MB ChB, MRCP, FRCPath

  2. Pharmacy Department, University College London Hospitals NHS Foundation Trust, London, NW1 2PG, UK

    Carolyn Gates MBChB,BPharm(Hons),MSc,MRPharmS & Fiona Maguire BPharm, ClinDipPharm, MRPharmS

Authors
  1. Anja B. Drebes MB ChB, MRCP, FRCPath
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carolyn Gates MBChB,BPharm(Hons),MSc,MRPharmS
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fiona Maguire BPharm, ClinDipPharm, MRPharmS
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anja B. Drebes MB ChB, MRCP, FRCPath .

Editor information

Editors and Affiliations

  1. Department of Haematology, University College London Hospitals NHS Foundation Trust, London, United Kingdom

    Hannah Cohen

  2. Institute for Women's Health, University College London Hospitals NHS Foundation Trust, London, United Kingdom

    Patrick O'Brien

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer-Verlag London

About this chapter

Cite this chapter

Drebes, A.B., Gates, C., Maguire, F. (2015). Anticoagulants and Antiplatelet Agents in Pregnancy. In: Cohen, H., O'Brien, P. (eds) Disorders of Thrombosis and Hemostasis in Pregnancy. Springer, Cham. https://doi.org/10.1007/978-3-319-15120-5_2

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-15120-5_2

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-15119-9

  • Online ISBN: 978-3-319-15120-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation