Low-molecular-weight heparins in pregnancy

We conducted a systematic review, with MEDLINE and Cochrane Library data base searches and bibliographic reviews, of English-language reports describing therapy with low-molecular-weight heparin (LMWH) in pregnancy. Altogether 40 citations, excluding abstracts, were identified. When the quality of evidence was categorized according to the method outlined by the U.S. Preventive Services Task Force, 2 articles were level I, 3 were level II-1, 3 were level II-2, 4 were level II-3, 9 were level III, and the remaining 19 were classified as other (i.e., below level III). Of the 728 pregnant women and 1 postpartum woman described in the 40 citations, 340 (47%) received dalteparin, 192 (26%) enoxaparin, 108 (15%) certoparin, 54 (7%) nadroparin, 30 (4%) other LMWH, and 6 (< 1%) unspecified. The indication for LMWH in most patients (606 pregnancies, 83%) was for thromboprophylaxis. Daily doses ranged from 2500-22,000 U for dalteparin, 20 mg (2000 U)-80 mg (8000 U) for enoxaparin, 3000 U for certoparin, and 2050-15,000 U for nadroparin. Regimens included fixed dosages, increasing dosages as pregnancy progressed, dosages based on body weight, and dosages titrated according to anti-Xa levels. Duration of therapy ranged from a single dose to 476 days. Maternal anti-Xa levels were reported for 255 pregnancies. Target anti-Xa levels ranged from 0.1-0.6 U/ml and measured values from 0.0-0.7 U/ml. Major maternal findings were 18 local and generalized skin reactions, 27 bleeding complications, 9 thromboembolic events, 8 deep vein thromboses, 1 bilateral renal vein thrombosis, 4 pulmonary emboli, 1 hepatic infarction, 4 cases of thrombophlebitis, 12 cases of preeclampsia, 1 placental abruption, and 2 osteoporotic vertebral fractures. A major fetal finding was lack of anti-Xa activity in fetal or cord blood. Published experience suggests that LMWHs are generally safe and effective when administered for thromboprophylaxis during pregnancy. Until prospective, randomized, controlled trials comparing them with unfractionated heparin are performed, their benefits in pregnancy will remain inconclusive.