Low-Molecular-Weight Heparin Fails to Boost Live Birth Rates in Women with Recurrent Miscarriage

Antithrombotic medications are often prescribed to women with histories of unexplained recurrent miscarriages, although there is little evidence of the efficacy of this approach. But the use of low-molecular-weight heparin (LMWH) in non-thrombophilic women with unexplained recurrent miscarriages did not improve live birth rates, according to a report in Blood.

Given these results, clinicians should stop prescribing LMWH in this particular patient population, lead investigator Elisabeth Pasquier, MD, of Brest University Hospital in Brest, France, told ASH Clinical News.

The theory that women with recurrent miscarriages and negative tests for antiphospholipid antibodies (or negative tests for inherited thrombophilia) may have some other blood clotting disorder resulted in the use of LMWH therapy among these patients, Dr. Pasquier explained.

Dr. Pasquier and colleagues conducted a randomized, double-blind, placebo-controlled trial of enoxaparin in 256 women with a history of two or more consecutive miscarriages before 15 weeks gestation and a negative thrombophilia work-up at 13 French hospital centers from April 2007 to October 2012. About 70 percent of the women had three or more consecutive miscarriages.

Most of the patients were early in their pregnancy, between 5 to 6 weeks’ gestation, at the time of study enrollment. After training for self-injection, the participants were randomly assigned to receive enoxaparin 40 mg or saline-solution placebo daily. Baseline characteristics were similar among the groups.

Therapy began on the enrollment visit and continued until 35 weeks’ gestation. Patients maintained a log of their injection site and treatment time on a daily basis to ensure protocol compliance.

Nearly 70 percent of all women in the study had a live and viable birth, the study’s primary outcome: 66.6 percent of the enoxaparin patients and 72.9 percent of the placebo patients.

The rates of live and viable births did not differ significantly between groups (absolute difference in live-birth rates = –6% [95% CI −17.1 to 5.1; p = 0.34]), the researchers noted. There were also no significant differences in secondary outcomes (rates of miscarriage, obstetric complications, maternal thrombocytopenia, bleeding episodes, and skin reaction) among the groups.

Over the course of the study, 30.4 percent of the enoxaparin group and 23.7 percent of the placebo group had another miscarriage (RR = 1.28, 95% CI 0.85 to 1.93), with the majority (84.3%) occurring before ten weeks’ gestation.

“Prophylactic doses of LMWH do not improve the chance of a live birth in non-thrombophilic women with unexplained recurrent miscarriage and should consequently no longer be routinely prescribed in this clinical setting,” the researchers stated.

Asked if aspirin may prove more effective in this patient population, Dr. Pasquier explained that the Scottish Pregnancy Intervention (SPIN) study, which assessed LWMH and low-dose aspirin in women with recurrent miscarriage, “showed no efficacy of open-label LMWH plus aspirin versus intense pregnancy surveillance alone.”

“However, because a detrimental effect of aspirin could not be ruled out and might explain the lack of efficacy of the combination with LMWH, it was important to investigate the effect of LMWH alone – as we did in our study,” she added.


References

  • Pasquier E, de Saint Martin L, Bohec C, et al. Enoxaparin for prevention of unexplained recurrent miscarriage: a multicenter randomized double-blind placebo-controlled trial. Blood. 2015 January 30. [Epub ahead of print]
  • Clark P, Walker ID, et al. SPIN (Scottish Pregnancy Intervention) study: a multicenter, randomized controlled trial of low-molecular-weight heparin and low-dose aspirin in women with recurrent miscarriage. Blood. 2010 May 27. [Epub ahead of print]

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