New Possible Cause for Unexplained Miscarriages

Researchers at St. Michael’s Hospital in Toronto, Ont., Canada, have identified a potential new cause for unexplained miscarriages in mice. In addition, they have identified two possible treatments to prevent these miscarriages, which have broader implications for the development of new drugs to treat heart attacks and strokes.

The researchers found that the same kind of blood clotting in coronary arteries or blood vessels in the brain that causes heart attacks and strokes also happens in the placenta. The massive clotting can destroy the placenta, block blood flow to the fetus and cause miscarriages. This condition is known as fetal and neonatal immune thrombocytopenia (FNIT), a bleeding disorder that affects between one in 800 and one in 1,500 live births (most commonly among Caucasians) in which mothers generate antibodies that attack and destroy platelets in their fetuses and newborns. In severe cases, FNIT may lead to bleeding in the brains of the fetuses and newborns and cause neurological impairment or even death.

Seventy-five percent to 95 percent of FNIT cases are caused by maternal antibodies to one specific platelet antigen, HPA-1. However, these researchers discovered that another antigen, HPA-2, causes a type of FNIT never described before that can lead to miscarriages in more than 83 percent of mice. They also discovered that the HPA-2 antibodies sometimes not only destroy platelets, but activate them and cause massive clotting in the placentas. Because only six to eight reported live human births in the world with FNIT caused by HPA-2 have been reported, this research suggests that the reason these cases are so rare is that most of the affected fetuses died through miscarriages before doctors examined them.

In mice, these miscarriages can be prevented using at least two therapies.One is the transfusion of immune globulin (IVIG). The other is the transfusion of an antibody known as anti-FcRn, which blocks the attacking maternal antibodies from crossing the placenta.

The research was reported in the November issue of the Journal of Clinical Investigation. It is hoped that the findings will be important in the development of safer antithrombotic drugs, which are under development by several companies.