Low Molecular Weight Heparin as Thromboprophylaxis in Pregnancy

Thomas Wahlberg, MD, Besvärsv 5, S-194 40 Upplands väsby (Sweden) Sir, Low molecular weight (LMW) heparins are gradually replacing heparin in the main thromboprophylaxis indication of medium-and high-risk surgery for prevention of thromboembolism. However, since these products have been on the market for only the last years, there exist limited data as to the safety of these drugs in long-term use. Controlled studies with heparin for thromboprophylaxis in pregnancy are practically nonexisting, however, due to the fact that heparin does not cross the placental barrier, it is preferred to oral anticoagulants. Not only with anticoagulants but also with heparin significant malformation rates could occur [ 1 ]. This might be related to the general high-risk profile in pregnant women with a thrombotic disposition. Heparin is also associated with osteoporosis [2]. Since heparin has to be injected at least twice daily and should continuously be monitored by coagulation assays during the later stages of pregnancy, there is a need of more convenient and safe antithrombotic drugs. A possible candidate would be LMW heparins because they do not cross the placental barrier [3] and could have a lower risk of osteoporosis than heparin [4]. Before planning controlled studies with LMW heparin, we made a retrospective analysis comprising 184 pregnant women obtaining the LMW heparin Fragmin (Dalteparin, Kabi Pharmacia) for thromboprophylaxis in 14 European obstetric clinics. The primary objective was to obtain a crude estimation of the safety/efficacy profile in comparison with heparin. We used a specially designed questionnaire where demographic data and medical history, focused on thrombosis risk, were asked for. The LMW heparin dosages and existing anti-FXa measurements, both in patients and newborn children were noted, together with thromboembolic, bleeding, and other adverse events as well as obstetric complications. Fragmin was used in a low dose, 2,500 IU, in 65% of the given treatments. 5,000 IU was used in 27% of the medication periods and higher dosages (7,200-16,000 IU) were only given in 8% of all Fragmin treatments. The median thromboprophylactic period was 42.5 days (range 1-476). Only in 36 patients, assessments of anti-FXa were made and only 24 patients had their dosages changed (19 were increased and 5 decreased). The criteria for dose adjustments were not possible to estimate in this study. No placental passage of anti-FXa was found (9 patients investigated). One child, but no mother died. The malformation rate was 3.3%, which would not be abnormal in pregnant patients, needing thromboprophylaxis [5]. Four