Comment: The quality of evidence is downgraded by study quality (unclear allocation concealment and lack of blinding), by inconsistency (heterogeneity in interventions and outcomes), and by imprecise results (limited study size for each compariosn).
Summary
SummaryA Cochrane review included 19 studies but only 16 studies with a total of 2 592 women contributed data to the review. Six of them compared methods of antenatal prophylaxis; low molecular weight heparin (LMWH) versus unfractionated heparin (UF) (4 studies), and heparin versus no treatment/placebo (2 studies). Nine studies assessed postnatal prophylaxis after caesarean section; one compared hydroxyethyl starch (HES) with UF, 4 compared heparin with placebo, 3 compared LMWH with UF, and one compared five-day versus 10-day LMWH. One study examined prophylaxis in the postnatal period (including following vaginal births).
For antenatal prophylaxis, none of the included trials reported on maternal mortality, and no differences were detected for the other primary outcomes of symptomatic thromboembolic events, symptomatic pulmonary embolism (PE) and symptomatic deep venous thrombosis (DVT) when LMWH or UFH was compared with no treatment/placebo or when LMWH was compared with UFH. The risk ratios for symptomatic thromboembolic events were: antenatal LMWH/UFH versus no heparin, RR 0.33 (95% CI 0.04 to 2.99; 2 studies, n=56); and antenatal LMWH versus UFH, RR 0.47 (95% CI 0.09 to 2.49; 4 studies, n=404). No differences were shown when antenatal LMWH or UFH was compared with no treatment/placebo for any secondary outcomes. Antenatal LMWH was associated with fewer adverse effects sufficient to stop treatment (RR 0.07, 95% CI 0.01 to 0.54; 2 studies, n=226), and fewer fetal losses (RR 0.47, 95% CI 0.23 to 0.95; 3 studies, n=343) when compared with UFH. In two studies, antenatal LMWH compared with UFH was associated with fewer bleeding episodes (defined in one trial of 121 women as bruises > 1 inch, RR 0.18, 95% CI 0.09 to 0.36; and in one trial of 105 women as injection site haematomas of ≥ 2 cm, bleeding during delivery or other bleeding, RR 0.28, 95% CI 0.15 to 0.53), however in a further trial of 117 women no difference between groups was shown for bleeding at delivery.
For post-caesarean/postnatal prophylaxis, only one trial comparing five-day versus 10-day LMWH after caesarean section reported on maternal mortality, observing no deaths. No differences were seen across any of the comparisons for the other primary outcomes (symptomatic thromboembolic events, symptomatic PE and symptomatic DVT). The RRs for symptomatic thromboembolic events were: post-caesarean LMWH/UFH versus no heparin, RR 1.30 (95% CI 0.39 to 4.27; 4 studies, n=840); post-caesarean LMWH versus UFH, RR 0.33 (95% CI 0.01 to 7.99; 3 studies, n=217); post-caesarean five-day versus 10-day LMWH, RR 0.36 (95% CI 0.01 to 8.78; 1 study, n=646); postnatal UFH versus no heparin, RR 0.16 (95% CI 0.02 to 1.36; 1 study, n=210). For prophylaxis after caesarean section, in one study (n=580), women receiving UFH and physiotherapy were more likely to have bleeding complications than women receiving physiotherapy alone (RR 5.03, 95% CI 2.49 to 10.18). In two additional trials, that compared LMWH with placebo, no difference between groups in bleeding episodes were detected. No other differences in secondary outcomes were shown when LMWH was compared with UFH post-caesarean, nor when post-caesarean HES was compared with UFH, post-caesarean five-day LMWH was compared with 10-day LMWH, or when UFH was compared to no heparin postnatally.
Clinical comment
Clinical commentIn the absence of clear randomised controlled trial evidence practitioners must rely on consensus-derived clinical practice guidelines or recommendations.