Low-molecular-weight heparins in pregnancy

We conducted a systematic review, with MEDLINE and Cochrane Library data ba se searches and bibliographic reviews, of English-language reports describi ng therapy with low-molecular-weight heparin (LMWH) in pregnancy. Altogethe r 40 citations, excluding abstracts, were identified. When the quality of e vidence was categorized according to the method outlined by the U.S. Preven tive Services Task Force, 2 articles were level I, 3 were level II-1, 3 wer e level II-2, 4 were level II-3, 9 were level III, and the remaining 19 wer e classified as other (i.e., below level III). Of the 728 pregnant women an d 1 postpartum woman described in the 40 citations, 340 (47%) received dalt eparin, 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 ran ged from 2500-22,000 U for dalteparin, 20 mg (2000 U)-80 mg (8000 U) for en oxaparin, 3000 U for certoparin, and 2050-15,000 U for nadroparin. Regimens included fixed dosages, increasing dosages as pregnancy progressed, dosage s based on body weight, and dosages titrated according to anti-Xa levels. D uration 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 finding s were 18 local and generalized skin reactions, 27 bleeding complications, 9 thromboembolic events, 8 deep vein thromboses, 1 bilateral renal vein thr ombosis, 4:pulmonary emboli, 1 hepatic infarction, 4 cases of thrombophlebi tis, 12 cases of preeclampsia, 1 placental abruption, and 2 osteoporotic ve rtebral fractures. A major fetal finding was lack of anti-Xa activity in fe tal or cord blood. Published experience suggests that LMWHs are generally s afe and effective when administered for thromboprophylaxis during pregnancy . Until prospective, randomized, controlled trials comparing them with unfr actionated heparin are performed, their benefits in pregnancy will remain i nconclusive.