Thromboprophylaxis with low molecular weight heparin (Fragmin) in high risk pregnancies

TLDR: LWM heparin (Fragmin) appears to be efficacious in preventing recurrent thromboembolic disease in pregnant women at high risk, but it is notable that osteoporotic fractures occurred post partum in one woman.

Abstract: Venous thromboembolic disease remains the commonest cause of maternal death. The management of thromboprophylaxis in high risk women during pregnancy is contentious. Low molecular weight heparins (LMW) have theoretical advantages compared with unfractionated heparin and warfarin but have been poorly studied in pregnancy. We report on the use of LMW heparin (Fragmin) as thromboprophylaxis in thirty four high risk pregnancies. All the women had a previous thrombosis or a thrombosis in their current pregnancy +/- a recognised thrombophilic state (eleven had the antiphospholipid syndrome). Fragmin was given subcutaneously to maintain trough anti-Xa activity of 0.15-0.2 U/ml and 2 h post injection levels of 0.4-0.6 U/ml. The levels were checked monthly during pregnancy. Most women required 5,000U Fragmin once daily during the first trimester unless they were greater than 100 kg at the start of pregnancy. The mean time for dosage increase was 20.5 week (S.D. 8.2). 26/34 pregnancies (76%) required 5,000 twice daily at the end of pregnancy. Epidural anaesthesia was managed by omitting Fragmin dose or inserting the needle 6 hours after the previous Fragmin injection. There were no thromboembolic events thrombocytopenias or excessive haemorrhage. One woman had osteoporotic vertebral collapse post partum, she had no other risk factors for osteoporosis. LWM heparin (Fragmin) appears to be efficacious in preventing recurrent thromboembolic disease in pregnant women at high risk, but it is notable that osteoporotic fractures occurred post partum in one woman. Further trials are required to determine optimal dosage and safety.