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LMWH does not improve pregnancy outcomes for women with thrombophilia, prior miscarriages
Low–molecular-weight heparin did not appear to confer any benefit for the prevention of recurrent pregnancy loss in women with inherited thrombophilia, according to the results of a systematic review and meta-analysis.
“We now have a solid evidence base to not use low–molecular-weight heparin [LMWH] to prevent pregnancy loss in thrombophilic women with prior late pregnancy loss,” Marc A. Rodger, MD, MSc, FRCPC, professor of medicine, chief and chair of hematology, and head of the thrombosis program at University of Ottawa, told HemOnc Today. “We can also stop performing costly thrombophilia testing in women with prior pregnancy loss if there is no beneficial therapy that can be offered to them.”
Defined as three or more consecutive miscarriages, recurrent pregnancy loss affects 1% of all women. Although half of these cases occur with no cause identified, inherited and acquired thrombophilias have been evaluated as a potential cause for pregnancy loss, according to study background.
Thus, Rodger and colleagues sought to observe whether prophylactic LMWH reduced the risk for loss of pregnancy in women with inherited thrombophilia.
They searched Medline, Embase and other relevant medical databases for randomized controlled trials of women with inherited thrombophilia and prior late ( 10 weeks) or early (< 10 weeks) pregnancy loss, assigned to LMWH or no LMWH.
The researchers identified eight trials that met their inclusion criteria, which included data from 483 women. Four trials included an arm combining LMWH with aspirin, and five trials included a LMWH-monotherapy arm. The control arms of these trials included aspirin only, placebo or no treatment.
Rodger and colleagues observed no significant differences in the rate of live birth among women assigned LMWH compared with women assigned no LMWH (RR = 0.81; 95% CI, 0.55-1.19).
A sensitivity analysis including only multicenter trials further showed no significant differences in outcomes (RR = 1.04; 95% CI, 0.93-1.16).
Similar results persisted in subgroup analyses of women with late pregnancy loss (RR = 0.81; 95% CI, 0.38-1.72) and recurrent pregnancy loss (RR = 0.97; 95% CI, 0.8-1.19).
The researchers acknowledged study limitations, including the relatively small patient cohort and the inclusion of studies that assigned LMWH in combination with aspirin.
“Our results will be surprising to many physicians and policy-makers who have long assumed that LMWH prevents pregnancy loss in this high-risk patient population,” Rodger said. “These doctors have routinely prescribed this expensive and burdensome therapy. Further trials are needed to gain confidence in the recommendation that LMWH use should not be prescribed to women with thrombophilia who have experienced recurrent early pregnancy loss.” – by Cameron Kelsall
For more information:
Marc A. Rodger, MD, MSc, FRCPC, can be reached at mrodger@ohri.ca.
Disclosure: Rodger reports grant support from Boehringer Ingelheim, as well as a paid expert position with the Canadian Agency for Drugs and Technologies in Health. Other researchers report grant support and/or honoraria from Leo Pharma, Pfizer and Sanofi Aventis.