Heparin-Induced Thrombocytopenia-Alternative Anticoagulation in Pregnancy and Lactation

Edelgard Lindhoff-Last; Rupert Bauersachs

doi:10.1055/s-2002-35284

Seminars in Thrombosis and Hemostasis, Inhaltsverzeichnis

Semin Thromb Hemost 2002; 28(5): 439-446
DOI: 10.1055/s-2002-35284

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

Abstract

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

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Referenzen

REFERENCES

1 Toglia M R, Weg J G. Venous thromboembolism during pregnancy. N Engl J Med . 1996; 335 108-114
2 Barbour L A. Current concepts of anticoagulant therapy in pregnancy. Obstet Gynecol Clin North Am . 1997; 24 499-521
3 Ginsberg J S, Hirsh J. Use of antithrombotic agents during pregnancy. Chest . 1998; 114 524-530
4 Brenner B. Inherited thrombophilia and fetal loss. Curr Opin Hematol . 2000; 7 290-295
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
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
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
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
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
10 Copplestone A, Oscier D G. Heparin-induced thrombocytopenia in pregnancy (Letter). Br J Haematol . 1987; 65 248
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
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
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
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
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
16 Taylor A A. Successful use of heparinoids in a pregnancy complicated by allergy to heparin. Br J Obstet Gynaecol . 2001; 108 1011-1012
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
18 Bartz C, Rath W. R-hirudin plasma levels are not affected by pregnancy (Abst). Int Angiol . 2001; 20 11
19 Calhoun B C, Hesser J W. Heparin-associated antibody with pregnancy: discussion of two cases. Am J Obstet Gynecol . 1987; 156 964-966
20 Lindhoff-Last E, Willeke A, Thalhammer C, Bauersachs R. Hirudin treatment in a breastfeeding woman. Lancet . 2000; 355 467-468
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
22 Chong B H. Low molecular weight heparinoid and heparin-induced thrombocytopenia (Abst). Aust NZ J Med . 1996; 26 331
23 Magnani H N. Orgaran (danaparoid sodium) use in the syndrome of heparin-induced thrombocytopenia. Platelets . 1997; 8 74-81
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
25 Greinacher A, Janssens U, Berg G. Lepirudin (recombinant hirudin) for parenteral anticoagulation in patients with heparin-induced thrombocytopenia. Circulation . 1999; 100 587-593
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
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
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
29 Meuleman D G. Orgaran (Org 10172): its pharmacological profile in experimental models. Haemostasis . 1992; 22 58-65
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
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
32 Danhof M, de Boer A, Magnani H N, Stiekema J CJ. Pharmacokinetic considerations on Orgaran (Org 10172) therapy. Haemostasis . 1992; 22 73-84
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
34 Harrison S J, Rafferty I, McColl M D. Management of heparin allergy during pregnancy with danaparoid. Blood Coagul Fibrinolysis . 2001; 12 157-159
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
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
37 Markwardt F, Fink G, Kaiser B. Pharmacological survey of recombinant hirudin. Pharmazie . 1988; 43 202-207
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
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
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
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
42 Aijaz A, Nelson J, Naseer N. Management of heparin allergy in pregnancy. Am J Hematol . 2001; 67 268-269
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
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
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
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
47 Ginsberg J S, Greer I, Hirsh J. Use of antithrombotic agents during pregnancy. Chest . 2001; 119 122-131
48 Clark S I, Porter T F, West F G. Coumarin derivatives and breast-feeding. Obstet Gynecol . 2000; 95 938-940
49 Le Orme L M, Lewis J, de Swiet M. May mothers given warfarin breast-feed their infants?. BMJ . 1977; 1 1564-1565
50 McKenna R, Cole B R, Vasan U. Is warfarin sodium contraindicated in the lactating mother?. Pediatrics . 1983; 103 325-327