Venous Thromboembolism Treatment with Low-Molecular-Weight Heparin during Pregnancy: A Systematic Review.

Introduction Low-molecular-weight heparin (LMWH) has become the standard therapy for managing acute venous thromboembolism (VTE) during pregnancy. In the UK, Europe and Australasia, LMWH is widely used for the treatment of both deep-vein thrombosis and pulmonary embolism occurring during pregnancy, and this practice is endorsed by a peer-reviewed Royal College of Obstetricians and Gynaecologists (RCOG) guideline. However, there are currently no LMWHs licensed for use during pregnancy, and efficacy and safety data are derived mostly from small case series. Our aim was to evaluate the efficacy and safety of LMWH for VTE treatment during pregnancy by performing a systematic review of data from published literature.

Methods Data from published studies included in this systematic review were identified by searching MEDLINE and EMBASE up to the end of 2003. The reference lists from identified articles were also hand searched. Data on the LMWH treatment regime, VTE recurrence, and side effects of VTE treatment were extracted and entered into pre-piloted forms.

Results Sixteen studies (including six case reports) reporting 177 patients were included. One hundred and eight (61%) women were treated with enoxaparin, 49 (28%) with dalteparin and 20 (11%) with nadroparin. In 31 (18%) cases, VTE was initially treated with unfractionated heparin for two days to two weeks after diagnosis. LMWH was administered twice daily in 154 (87%) cases. Recurrent VTE was reported in three (1.7%) women: one receiving dalteparin 10,000 IU od, one receiving enoxaparin 40 mg bd, and one receiving enoxaparin 1mg/kg bd. There were no maternal deaths. Severe maternal bleeding occurred in three (1.7%) women. In two cases, the LMWH could have contributed to the extent of bleeding originating primarily from obstetric causes, and in the other from epistaxis. Minor allergic reactions occurred in two (1.1%) women, thrombocytopenia (unrelated to LMWH) in one (0.6%) woman, and osteoporosis in none.

Conclusion Our findings are consistent with LMWH being both effective and safe in the treatment of acute VTE during pregnancy.