Does having an inhibitor increase the risk of death among US males with severe hemophilia A?

People with hemophilia lack a protein (a clotting factor) necessary for blood to clot normally. This can lead to spontaneous bleeding as well as bleeding following injuries or surgery. The best way to treat hemophilia is to replace the missing blood clotting factor so that the blood can clot properly. This is done by infusing (giving through a needle into a vein) commercially prepared factor. However, up to 1 in 5 people with hemophilia develop an antibody (inhibitor) to the infused factor used to treat bleeding episodes. An inhibitor prevents the factor from working to stop bleeding and makes treatment for bleeding episodes much more difficult and expensive. While all people with hemophilia are at risk for developing an inhibitor, those with severe hemophilia are more likely to develop one than those with mild or moderate hemophilia. People with inhibitors are at increased risk for joint disease and other complications from bleeding, including death. Routine screening for inhibitors with a blood test can be lifesaving as it helps find inhibitors early when they are more likely to be treated successfully.

About this Study

CDC’s Division of Blood Disorders and Hemophilia Treatment Center (HTC) network investigators conducted a study among 7,386 U.S. males with severe hemophilia A over a 13-year period to see if having an inhibitor placed them at an increased risk of death. Hemophilia A is an inherited condition (runs in families), but because of the way it is inherited, most people affected with Hemophilia A are male. This study, published in the American Journal of Hematology used data from the Universal Data Collection System collected between May, 1998 and September 30, 2011, and information on patient deaths reported to CDC on mortality forms completed by HTC staff. During the study period, 432 participants died, among whom 48 were patients with an inhibitor. We invite you to read the study’s abstract here.

Main Findings from this Study

• Males with severe hemophilia A who have an inhibitor are at increased risk of death.
• Males with an inhibitor were 70% more likely to die compared to those without an inhibitor, even when other risks for death such as older age, liver disease, and infection with either HIV (the virus that causes AIDS) or hepatitis C virus were taken into account.
• Of the 48 patients with an inhibitor who died, 42% had a hemophilia-related cause of death (due to a bleeding complication) whereas only 12% of patients without an inhibitor died of a bleeding related complication.

Critical Gaps & Future Directions

More information is needed about the factors that increase a person’s risk for an inhibitor, so that strategies can be developed to prevent inhibitors from occurring. CDC is partnering with the U.S. Hemophilia Treatment Center Network by performing blood tests to screen for inhibitors in patients enrolled in the Community Counts Program. The results of this testing will be used to determine the number of people with inhibitors in the U.S. hemophilia population and collect information about when they occur. Routine screening through this program or a Hemophilia Treatment Center may uncover an inhibitor early in its development when treatment to eliminate it is more likely to be successful.

More Information

Please visit the following links for more information about:

Hemophilia: https://www.cdc.gov/ncbddd/hemophilia/index.html

Inhibitors: https://www.cdc.gov/ncbddd/hemophilia/inhibitors.html

Research on inhibitors: https://www.cdc.gov/ncbddd/hemophilia/features/inhibitors.html and https://www.cdc.gov/ncbddd/hemophilia/research.html

Inhibitor testing: http://www.hemophilia.org/Newsroom/Medical-News/CDC-Hosts-Inhibitor-Testing-Webinar

Paper Reference

Walsh, C.E., Soucie, J.M., Miller, C.H. and the Hemophilia Treatment Center Network Investigators (2015), Impact of inhibitors on hemophilia A mortality in the United States. American Journal of Hematology. doi: 10.1002/ajh.23957.