Accumulation of low molecular mass heparin during prophylactic treatment in pregnancy

A history of thromboembolism is associated with an increased risk of new thromboembolic events during pregnancy. Prophylaxis with heparin during pregnancy implicates long-term treatment with daily injections with either unfractionated heparin (UFH) or low molecular mass heparin (LMMH). Prolonged treatment with heparin may result in endothelial absorption and drug accumulation. In order to test this hypothesis, anti-FXa activity during pregnancy was measured in four women allergic to conventional UFH, who were treated with LMMH (dalteparin; Pharmacia). It was found that, at the commencement of treatment, it took more than 8 days to reach a steady maximum peak value, located 3 h after the given dose. One daily dosage of 5,000 IU anti-Xa resulted in a measurable level of FXa for 24 h in pregnancy week 40, compared with 17h at pregnancy week 37. The implications of an elevated anti-FXa activity during pregnancy, especially during the third trimester and at partus, are discussed. We present a reduced dose regime near term and during delivery.