Lepirudin in Pregnancy

Data on the treatment of HIT during pregnancy are limited (Lindhoff-Last and Bauersachs, 2002). In general, the use of lepirudin during pregnancy is not recommended, as it crosses the placenta. Zebrafish experiments indicate that thrombin has an important role in early embryogenesis and that inhibition by lepirudin may cause cell regulation defects (Jagadeeswaran et al., 1997). Experiments in rabbits showed a fetal hirudin plasma concentration that was 1/60th that of the maternal concentration (Markwardt et al., 1988), and embryotoxic effects were seen in rabbits at high, but not low, doses (30 mg/kg/day vs. 1-10 mg/kg/ day, respectively) (Berlex Laboratories, data on file).

A pregnant woman with systemic lupus erythematosus who was treated with dalteparin developed HIT at week 25. Her platelet count dropped from 230 to 59 X 10 /L, after which she was treated with lepirudin (15 mg sc twice daily), with aPTT and ECT used to monitor her dosage. Following delivery by cesarean section, she experienced no postpartum bleeding complications, and treatment with lepirudin was continued for several weeks thereafter (Huhle et al., 2000b). Another pregnant woman with lupus anticoagulant and HIT was successfully treated for 36 wk with lepirudin.

A case report described a breastfeeding woman diagnosed with HIT who was treated with sc lepirudin, 50 mg twice daily (Lindhoff-Last et al., 2000a). No lepirudin was detected in her breast milk, although plasma levels were within therapeutic range. Neither bleeding nor thrombosis occurred in mother or infant.

Lepirudin and danaparoid are each classified by the FDA as pregnancy category B, based on limited animal data. However, danaparoid does not cross the placenta, and it has been used for prophylaxis and therapy of HIT during pregnancy (Greinacher et al., 1993; Dager and White, 2002) (see Chapters 12 and 13).

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