(May 23, 2011—Toronto, ON) In the first study of its kind, Mount Sinai Hospital researchers have discovered a new mechanism for a common blood thinning drug to prevent severe high blood pressure in pregnancy, and the ensuing, potentially fatal effects on a developing baby.
The study was published online today in the leading medical journal Obstetrics and Gynecology.
Heparin is an anticoagulant commonly used to prevent or treat blood clots. In pregnancy, the drug is often prescribed in lower doses, in an attempt to prevent recurrent miscarriages and other pregnancy-related complications that are thought to be due to placental blood clots, or thrombosis. However, the exact mechanism by which the drug exerts its effects in pregnant women with severe pregnancy-related high blood pressure (a serious condition called pre-eclampsia) was unknown.
“Our new findings have considerable significance for the use of heparin to prevent serious pregnancy-related complications,” said senior study author Dr. John Kingdom, Maternal Fetal-Medicine Specialist in the Department of Obstetrics and Gynaecology at Mount Sinai Hospital and a scientist at the hospital’s Samuel Lunenfeld Research Institute. “Our data present a novel and exciting picture of exactly how heparin exerts its beneficial effects on the placenta to prevent the development of pre-eclampsia.”
In a woman with pre-eclampsia, tiny blood vessels surrounding the baby’s placenta (called placental villi) release natural inhibitory factors important for its growth but which interfere with the mother’s own blood vessels and increase her blood supply.
Dr. Kingdom and Mount Sinai colleagues Drs. Mara Sobel and Sascha Drewlo added regular and low molecular weight (shorter chains of the full molecule) forms of heparin to samples of placental villi from healthy women in early and late pregnancy, and from those with severe pre-eclampsia.
Surprisingly, the researchers found that placental villi from healthy early pregnancies have the same inhibitory effect on blood vessels, but it fades to normal as healthy pregnancy proceeds. Heparin completely reversed this effect in early pregnancy, and was able to restart a limited degree of new blood vessel growth (angiogenesis) in some of the pre-eclamptic pregnancies, thus reducing the risk of high blood pressure. Both forms of heparin were effective, but the more commonly used low molecular weight type of heparin had a more pronounced impact.
“In women with a previous history of severe pre-eclampsia, heparin significantly reduces the risk of recurrent disease. The mechanism of action is likely due to a direct action on blood vessels, rather than as an anticoagulant, or blood thinner,” said Dr. Kingdom. “Heparin is a complex molecule—we can remove the anticoagulant properties of the drug to make it potentially safer, and thus in the future attempt to reverse pre-eclampsia by giving higher doses of ‘optimized heparin’ that could restore better vascular function and lower blood pressure.” Dr. Kingdom added that a clearer understanding of how heparin works in pregnancy opens new avenues for more effective, safer use of the drug in other areas of obstetrics.”
He also noted that additional, larger studies will still need to be conducted to determine the full effects of heparin in women with, for example, mild cases of pre-eclampsia.
Pre-eclampsia occurs in about 7 to 10 per cent of pregnancies and may develop from 20 weeks’ gestation, often leading to pre-term delivery or poor fetal growth. Apart from Caesarean section or induction of labour, there is no known cure and previous drug approaches have been unsuccessful. It is the most common and dangerous pregnancy-related complication that affects both mother and unborn child.
The study received support from the Canadian Institutes of Health Research, the Rose Torno Chair at Mount Sinai Hospital and the Molly Towell Research Foundation of Canada.