Hemophilia Carriers at High Risk for Heavy Bleeding After Childbirth

Women who are hemophilia carriers are at a higher risk of experiencing heavy bleeding after giving birth, particularly those who are not on a prophylactic, or preventive, treatment regimen, a new review study has found.

Researchers say these findings indicate that more intensive preventive treatments might benefit carriers about to give birth.

The findings also highlight a need for more research into how best to care for these women as they go through pregnancy and childbirth.

The review study, “Maternal and neonatal bleeding complications in relation to peripartum management in hemophilia carriers: A systematic review,” was published in Blood Reviews.

Hemophilia type A and type B are both caused by mutations in genes found on the X chromosome. Since biological females usually have two copies of the X chromosome, it is possible for them to have one X chromosome with a hemophilia-causing mutation, while the other X chromosome has no mutation. Such individuals are said to be hemophilia “carriers,” because they do not have hemophilia themselves, but can still pass disease-causing genes to their biological children.

During pregnancy, the body enters a pro-coagulation or pro-clotting state in preparation for the bleeding that will occur during childbirth. During this state, there is an increase in the production of clotting factors — proteins that promote blood clotting — and a decrease in the production of anticoagulant factors, which prevent such clotting.

In hemophilia carriers, clotting factor levels do rise somewhat during pregnancy. But these levels are still generally much lower than those of women who are not carriers. As such, women who are hemophilia carriers may be at an increased risk of postpartum hemorrhage (PPH), or heavy bleeding following childbirth.

To better understand the risk of PPH in hemophilia carriers, and to assess strategies for managing these women during pregnancy and childbirth, researchers in the Netherlands conducted a review of published scientific literature.

The team reviewed data from 17 case reports and 11 group studies. Collectively, these studies described 502 deliveries, though individual patient data were not available for all births.

Notably, the researchers found these studies were generally of low quality, and that there was a high risk of publication bias — a phenomenon in which the type of outcome of a particular study influences the decision of whether or not it should be published and distributed within the scientific community.

“Overall poor quality evidence is available on peripartum [near-childbirth] management of carriers of hemophilia and therefore optimal peripartum management to prevent PPH remains to be elucidated by conducting larger prospective [group] studies,” the researchers wrote.

“National — and preferably international collaboration — is needed to collect sufficient data on available management strategies and outcome of pregnancy,” they wrote, adding that “only then, guidelines can be updated according to evidence based medicine to lower both the peripartum [pre-childbirth] maternal and neonatal [post-childbirth] bleeding risks.”

For 87 deliveries, there was available data on both prophylactic treatments and bleeds taking place around the time of birth.

Analyses of these deliveries showed the rate of PPH was significantly lower among individuals who were given preventive treatment, compared with those who were not (43.6% vs. 77.1%).

Common prophylactic treatments used included clotting factor concentrates (replacement therapies), blood products such as fresh frozen plasma, tranexamic acid, and desmopressin.

“The high risk for PPH seems apparent in hemophilia carriers,” the team wrote.

They noted that, while preventive treatment did seem beneficial, PPH was still common among women on prophylaxis. As such, “intensification of prophylactic management strategies during and after delivery seems prudent.”

Since carriers’ children may have hemophilia themselves, the researchers also assessed bleeding outcomes among newborns. A few instances of bleeding events in newborns were reported.

“But,” the researchers wrote, “insufficient information was provided to reliably investigate neonatal outcome in relation to management.”

The team noted that, among all cases of newborn bleeding reported, most occurred during assisted vaginal delivery — when a baby is born through the vaginal canal with the help of forceps or a vacuum device — or during an emergency cesarean section.

“Consequently, it remains preferable to avoid assisted vaginal delivery if possible and the pros and cons of an elective cesarean section should be discussed by healthcare providers with the hemophilia carrier to make a shared decision,” the researchers wrote.

Pain-blocking neuraxial techniques, such as epidural or spinal anesthetics, were generally not associated with bleeding events when clotting factor levels were sufficiently high (above 50 international units per deciliter). The researchers noted, however, that bleeding related to these techniques is very rare in general, and the number of patients with available data was “too low to ensure safety.”