Download PDF
Semin Thromb Hemost 2002; 28(5): 439-446
DOI: 10.1055/s-2002-35284
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Heparin-Induced Thrombocytopenia-Alternative Anticoagulation in Pregnancy and Lactation

Edelgard Lindhoff-Last, Rupert Bauersachs
  • Department of Internal Medicine, Division of Angiology, University Hospital Frankfurt, Germany
Further Information

Publication History

Publication Date:
06 November 2002 (online)

    Permissions and Reprints

ABSTRACT

Heparin-induced thrombocytopenia (HIT) appears rarely in pregnant patients who are being treated with heparin. When HIT is suspected, heparin treatment should be discontinued and alternative anticoagulation should be started. The heparinoid danaparoid appears to be the drug of choice for acute treatment and prophylaxis because of its low placental permeability. Between the 12th and 36th weeks of pregnancy, either danaparoid may be continued or warfarin may be used after recovery of platelet counts. Before and during delivery, danaparoid should be preferred over warfarin in order to avoid bleeding complications in mother and infant. Hirudin should only be used when either cross-reactivity with heparin-induced antibodies or cutaneous allergy against heparinoids are observed. Postpartum warfarin seems to be the treatment of choice because breast-feeding can be continued. Alternative treatment with either danaparoid or hirudin is possible, but data on treatment with these reagents in lactating mothers are very limited.

KEYWORDS

Pregnancy - lactation - danaparoid - hirudin - heparin-induced thrombocytopenia

REFERENCES

  • 1 Toglia M R, Weg J G. Venous thromboembolism during pregnancy.  N Engl J Med . 1996;  335 108-114
    CrossrefPubMedGoogle Scholar
  • 2 Barbour L A. Current concepts of anticoagulant therapy in pregnancy.  Obstet Gynecol Clin North Am . 1997;  24 499-521
    CrossrefPubMedGoogle Scholar
  • 3 Ginsberg J S, Hirsh J. Use of antithrombotic agents during pregnancy.  Chest . 1998;  114 524-530
    PubMedGoogle Scholar
  • 4 Brenner B. Inherited thrombophilia and fetal loss.  Curr Opin Hematol . 2000;  7 290-295
    CrossrefPubMedGoogle Scholar
  • 5 Warkentin T E, Sheppard J AI, Horsewood P. Impact of the patient population on the risk for heparin-induced thrombocytopenia.  Blood . 2000;  96 1703-1708
    CrossrefPubMedGoogle Scholar
  • 6 Warkentin T E. Clinical picture of heparin-induced thrombocytopenia. In: Warkentin TE, Greinacher A, eds. Heparin-Induced Thrombocytopenia New York: Marcel Dekker 2000: 43-81
    Google Scholar
  • 7 Van der Weyden B M, Hunt H, McGrath K. Delayed-onset heparin-induced thrombocytopenia. A potentially malignant syndrome.  Med J Aust   1983;  2 132-135
    PubMedGoogle Scholar
  • 8 Meytes D, Ayalon H, Virag I, Weisbort Y, Zakut H. Heparin-induced thrombocytopenia and recurrent thrombosis in pregnancy. A case report.  J Reprod Med . 1986;  31 993-996
    PubMedGoogle Scholar
  • 9 Henny C P, ten Cate H, ten Cate W J. Thrombosis prophylaxis in an AT III deficient pregnant woman: application of a low molecular weight heparinoid (Letter).  Thromb Haemost . 1986;  55 301
    PubMedGoogle Scholar
  • 10 Copplestone A, Oscier D G. Heparin-induced thrombocytopenia in pregnancy (Letter).  Br J Haematol . 1987;  65 248
    PubMedGoogle Scholar
  • 11 Van Besien K, Hoffman R, Golichowski A. Pregnancy associated with lupus anticoagulant and heparin-induced thrombocytopenia: management with a low molecular weight heparinoid.  Thromb Res . 1991;  62 23-29
    CrossrefPubMedGoogle Scholar
  • 12 Greinacher A, Eckhardt T, Mussmann J, Mueller-Eckhardt C. Pregnancy complicated by heparin associated thrombocytopenia: management by a prospectively in vitro selected heparinoid (Org 10172).  Thromb Res . 1993;  71 123-126
    CrossrefPubMedGoogle Scholar
  • 13 Gill J, Kovacs M J. Successful use of danaparoid in treatment of heparin-induced thrombocytopenia during twin pregnancy.  Obstet Gynecol . 1997;  90 648-650
    CrossrefPubMedGoogle Scholar
  • 14 Boshkov L K, Hamilton P, Lee A, Boldt K. Successful therapy of heparin-induced thrombocytopenia with thrombosis (HITTS) in pregnancy with danaparoid sodium (Orgaran) (Abst).  Blood . 1999;  94(Suppl 1) 102b
    PubMedGoogle Scholar
  • 15 Macchi L, Sarfati R, Guicheteau M. Thromboembolic prophylaxis with danaparoid (Orgaran) in a high-thrombosis-risk pregnant woman with a history of heparin-induced thrombocytopenia (HIT) and Widal's disease.  Clin Appl Thromb Hemost . 2000;  6 187-189
    PubMedGoogle Scholar
  • 16 Taylor A A. Successful use of heparinoids in a pregnancy complicated by allergy to heparin.  Br J Obstet Gynaecol . 2001;  108 1011-1012
    PubMedGoogle Scholar
  • 17 Huhle G, Geberth M, Hoffmann U, Heene D L, Harenberg J. Management of heparin-induced thrombocytopenia in pregnancy with subcutaneous r-hirudin.  Gynecol Obstet Invest . 2000;  49 67-69
    CrossrefPubMedGoogle Scholar
  • 18 Bartz C, Rath W. R-hirudin plasma levels are not affected by pregnancy (Abst).  Int Angiol . 2001;  20 11
    PubMedGoogle Scholar
  • 19 Calhoun B C, Hesser J W. Heparin-associated antibody with pregnancy: discussion of two cases.  Am J Obstet Gynecol . 1987;  156 964-966
    PubMedGoogle Scholar
  • 20 Lindhoff-Last E, Willeke A, Thalhammer C, Bauersachs R. Hirudin treatment in a breastfeeding woman.  Lancet . 2000;  355 467-468
    PubMedGoogle Scholar
  • 21 Warkentin T E, Levine M N, Hirsh J. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin.  N Engl J Med . 1995;  332 1330-1335
    CrossrefPubMedGoogle Scholar
  • 22 Chong B H. Low molecular weight heparinoid and heparin-induced thrombocytopenia (Abst).  Aust NZ J Med . 1996;  26 331
    PubMedGoogle Scholar
  • 23 Magnani H N. Orgaran (danaparoid sodium) use in the syndrome of heparin-induced thrombocytopenia.  Platelets . 1997;  8 74-81
    PubMedGoogle Scholar
  • 24 Greinacher A, Völpel H, Janssens U. Recombinant hirudin (lepirudin) provides safe and effective anticoagulation in patients with the immunologic type of heparin-induced thrombocytopenia: a prospective study.  Circulation . 1999;  99 73-80
    CrossrefPubMedGoogle Scholar
  • 25 Greinacher A, Janssens U, Berg G. Lepirudin (recombinant hirudin) for parenteral anticoagulation in patients with heparin-induced thrombocytopenia.  Circulation . 1999;  100 587-593
    CrossrefPubMedGoogle Scholar
  • 26 Lewis B E, Wallis D E, Berkowith S D, for the ARG-911 Study investigators. Argatroban anticoagulant therapy in patients with heparin-induced thrombocytopenia.  Circulation . 2001;  103 1838-1843
    CrossrefPubMedGoogle Scholar
  • 27 Greinacher A, Warkentin T E. Treatment of heparin-induced thrombocytopenia: an overview. In: Warkentin TE, Greinacher A, eds. Heparin-Induced Thrombocytopenia New York: Marcel Dekker 2000: 261-290
    Google Scholar
  • 28 Warkentin T E, Elavathil L J, Hayward C PM. The pathogenesis of venous limb gangrene associated with heparin-induced thrombocytopenia.  Ann Intern Med . 1997;  127 804-812
    CrossrefPubMedGoogle Scholar
  • 29 Meuleman D G. Orgaran (Org 10172): its pharmacological profile in experimental models.  Haemostasis . 1992;  22 58-65
    PubMedGoogle Scholar
  • 30 Vun C H, Evans S, Chong B H. Cross-reactivity study of low molecular weight heparins and heparinoid in heparin-induced thrombocytopenia.  Thromb Res . 1996;  81 525-532
    CrossrefPubMedGoogle Scholar
  • 31 Newman P M, Swanson R L, Chong B H. IgG binding to PF4-heparin complexes in the fluid phase and cross-reactivity with low molecular weight heparin and heparinoid.  Thromb Haemost . 1998;  80 292-297
    PubMedGoogle Scholar
  • 32 Danhof M, de Boer A, Magnani H N, Stiekema J CJ. Pharmacokinetic considerations on Orgaran (Org 10172) therapy.  Haemostasis . 1992;  22 73-84
    PubMedGoogle Scholar
  • 33 Peeters L LH, Hobbelen P MJ, Verkeste C M. Placental transfer of Org 10172, a low molecular weight heparinoid, in the awake late-pregnant guinea pig.  Thromb Res . 1986;  44 277-283
    CrossrefPubMedGoogle Scholar
  • 34 Harrison S J, Rafferty I, McColl M D. Management of heparin allergy during pregnancy with danaparoid.  Blood Coagul Fibrinolysis . 2001;  12 157-159
    CrossrefPubMedGoogle Scholar
  • 35 Greinacher A. Recombinant hirudin for the treatment of heparin-induced thrombocytopenia. In: Warkentin TE, Greinacher A, eds. Heparin-Induced Thrombocytopenia New York: Marcel Dekker 2000: 313-339
    Google Scholar
  • 36 Weitz J I, Hudoba M, Massel D, Marganore J, Hirsh, J. Clot bound thrombin is protected from inhibition by heparin-antithrombin III but is susceptible to inactivation by antithrombin III-independent inhibitors.  J Clin Invest . 1990;  86 385-391
    CrossrefPubMedGoogle Scholar
  • 37 Markwardt F, Fink G, Kaiser B. Pharmacological survey of recombinant hirudin.  Pharmazie . 1988;  43 202-207
    PubMedGoogle Scholar
  • 38 Huhle G, Song X, Wang L C, Hoffman U, Harenberg J. Generation and disappearance of antihirudin antibodies during treatment with r-hirudin.  Fibrinolysis Proteolysis . 1998;  12 91-113
    PubMedGoogle Scholar
  • 39 Pötzsch B, Madlener K, Seelig C. Monitoring of r-hirudin anticoagulation during cardiopulmonary bypass-assessment of the whole blood ecarin clotting time.  Thromb Haemost . 1997;  77 920-925
    PubMedGoogle Scholar
  • 40 Lindhoff-Last E, Piechottka G P, Rabe F, Bauersachs R. Hirudin determination in plasma can be strongly influenced by the prothrombin level.  Thromb Res . 2000;  100 55-60
    CrossrefPubMedGoogle Scholar
  • 41 Harenberg J, Hoffmann U, Liebe V. Treatment of a woman with a lupus syndrome and cutaneous allergy to heparins/heparinoids by subcutaneous r-hirudin throughout pregnancy (Abst).  Ann Hematol . 2001;  80 87
    PubMedGoogle Scholar
  • 42 Aijaz A, Nelson J, Naseer N. Management of heparin allergy in pregnancy.  Am J Hematol . 2001;  67 268-269
    CrossrefPubMedGoogle Scholar
  • 43 Hirsh J, Dalen J E, Anderson D R. Oral anticoagulants: mechanism of action, clinical effectiveness and optimal therapeutic range.  Chest . 1998;  114 445-469
    CrossrefPubMedGoogle Scholar
  • 44 Hall J G, Pauli R M, Wilson K M. Maternal and fetal sequelae of anticoagulation during pregnancy.  Am J Med . 1980;  68 122-140
    CrossrefPubMedGoogle Scholar
  • 45 Ginsberg J S, Hirsh J, Turner C, Levine N, Burrows R. Risks to the fetus of anticoagulant therapy during pregnancy.  Thromb Haemost . 1989;  61 197-203
    PubMedGoogle Scholar
  • 46 Chan W S, Anana S, Ginsberg J. Anticoagulation in women with mechanical heart valves. A systematic review of the literature.  Arch Intern Med . 2000;  160 191-196
    CrossrefPubMedGoogle Scholar
  • 47 Ginsberg J S, Greer I, Hirsh J. Use of antithrombotic agents during pregnancy.  Chest . 2001;  119 122-131
    CrossrefPubMedGoogle Scholar
  • 48 Clark S I, Porter T F, West F G. Coumarin derivatives and breast-feeding.  Obstet Gynecol . 2000;  95 938-940
    CrossrefPubMedGoogle Scholar
  • 49 Le Orme L M, Lewis J, de Swiet M. May mothers given warfarin breast-feed their infants?.  BMJ . 1977;  1 1564-1565
    PubMedGoogle Scholar
  • 50 McKenna R, Cole B R, Vasan U. Is warfarin sodium contraindicated in the lactating mother?.  Pediatrics . 1983;  103 325-327
    CrossrefPubMedGoogle Scholar