NEW YORK (Reuters Health) – For pregnant women who require chronic anticoagulation, low molecular weight heparin (LMWH) is an alternative to warfarin, but not an ideal one, according to a report in the November 1 American Journal of Cardiology.

Given that warfarin is known to pass through the placental barrier, causing fetal hemorrhage and malformations, many pregnant women are understandably reluctant to use it.

Their risks for cardiac and fetal complications will still be high with LMWH, however.

At the University of Toronto, Ontario, Canada, Dr. Candice K. Silversides and colleagues reviewed maternal and fetal outcomes in 23 pregnancies in 17 women with mechanical heart valves, all of whom were treated with LMWH and low-dose aspirin throughout their pregnancies.

Anti-Xa levels were monitored every two 2 to 4 weeks throughout all pregnancies, the authors note. LMWH was given subcutaneously twice daily to maintain 4-hour postinjection anti-Xa levels of 1 to 1.2 U/mL.

Fifteen pregnancies were in women with mechanical mitral valves and 9 were in women with mechanical aortic valves (including 1 pregnancy in a woman with both). Most women (96%) were asymptomatic before pregnancy and were in New York Heart Association functional class I.

There was one maternal thromboembolic event (4%) in a 37-year-old woman with an anti-Xa level of 1U/ml. Both mother and fetus died at 26 weeks. This woman had a history of bicuspid aortic valve disease, aortic insufficiency, and a dilated aortic root. Autopsy showed that her aortic valve thrombosis involved approximately half the valve circumference.

Other cardiac complications occurred in 5 pregnancies (22%), including arrhythmias in 3, pulmonary edema in 2, and endocarditis in 1. Three women had postpartum hemorrhage despite appropriate anti-Xa levels.

There were two first-trimester miscarriages. Excluding the two early miscarriages, a total of 9 pregnancies (39%) had fetal or neonatal adverse events, including 2 intrauterine fetal deaths at 21 and 34 weeks of gestation.

There were 19 live births (83%). The mean gestational age at delivery was 36 weeks. Four infants born at term were small for gestational age. Premature deliveries occurred in 4 pregnancies, including the one with maternal/fetal death.

Fifty-eight percent of the women delivered vaginally, the others delivered by cesarean section for obstetric reasons.

“The pharmacokinetics of LMWH have been shown to be altered during pregnancy,” the authors warn. “The clearance and the volume distribution of LMWH are higher during pregnancy, and consequently, the plasma concentration is significantly lower. Therefore, the administration of LMWH on the basis of weight alone is inadequate, and the measurement of anti-Xa levels is necessary to ensure effective anticoagulation.”

The researchers conclude that carefully monitored LMWH might be a “suitable” approach for anticoagulation in pregnant women who are unwilling to take warfarin.

Still, they acknowledge, “This group of women remains at risk for maternal cardiac and fetal complications.” Their experience, they add, “highlights current limitations with anticoagulation in this population.”

Reference:
Am J Cardiol 2009.