Study of Blood Inhibitors in Hemophilia Patients

Hemophilia is a disorder that causes blood not to clot properly, and because it is rare, it receives comparatively little funding for research. But for the estimated 20,000 people with hemophilia in the U.S., the health and economic effects of the disorder can be devastating.

Particularly challenged are the 7 to 10 percent of patients who develop antibodies, or inhibitors, which prevent the drugs used to treat their bleeds from working. Those with inhibitors are twice as likely to require hospitalization for bleeding. The costs for their hospital care are, on average, three to five times greater, with medical bills for many climbing above $1 million over a lifetime.

The problem is more serious than just a cut that won't stop bleeding. Hemophilia can lead to spontaneous internal bleeding that can cause severe damage to joints, organs and the neurological system.

Thanks to a CDC Foundation partnership with Baxter Bioscience and Pfizer Inc, a CDC team led by Michael Soucie, Ph.D., associate director of science for CDC’s Division of Blood Disorders, is closer to understanding why some people with hemophilia develop inhibitors and others don't.

"Understanding the risk factors for inhibitors will help to guide treatment for people at high risk for this complication and may lead to the development of products that are less likely to cause an inhibitor," says Soucie.

More Data Improves Patient Care

About 70 percent of all people with hemophilia in the U.S. receive some of their medical care from federally funded treatment centers located throughout the country. CDC already works closely with these centers to ensure the safety of blood products and to collect data on joint complications. Funding from the CDC Foundation partnership enabled CDC to expand this monitoring system to collect the additional blood specimens and data needed to study inhibitors.

Through the inhibitors study, researchers gather data from patients before an inhibitor develops and then closely analyze data from patients who later develop an inhibitor to determine which factors – like age, race/ethnicity, and frequency and type of treatment – are most strongly associated with inhibitor development. Another key factor is genotype, or the exact genetic mutation responsible for a person's hemophilia. There are more than 2,000 genotypes that cause hemophilia.

An initial $3 million grant from Wyeth Pharmaceuticals (now a part of Pfizer Inc) to the CDC Foundation in 2005 helped CDC launch a pilot study with 12 treatment centers. Following the successful pilot phase, in 2009 the CDC Foundation received $1.5 million from Baxter Healthcare Corporation and $1.5 million from Pfizer Inc to help CDC conduct the second phase of the study, adding five more treatment centers and a wider range of data collection and analyses. Most recently, Pfizer contributed an additional $800,000 to further expand genotype data collection.

“The advantage to what we’re doing is that it gives you the best scientific data. The down side is that it takes a long time and it’s expensive,” says Soucie. “There would be no way for outside partners to directly support our work were it not for the CDC Foundation.”

Digging Deep: Genetics May Hold Answer

A key component of the inhibitors study involves genotyping every participant. The resulting data have provided the first estimates of inhibitor risk by genotype for the U.S., allowing doctors to more accurately predict which patients are likely to develop inhibitors and take action to prevent complications. The data may also lead to better drugs to treat hemophilia.

“Drug manufacturers can change molecules of drugs, so knowing which molecules are most likely to trigger a problem allows them to make changes to lessen the risk,” says Soucie. “That’s a really unique factor of this study.”

The study has implications beyond hemophilia. Genotyping also holds the potential to inform research on treatments for everything from spina bifida and Down syndrome to muscular dystrophy. While rare disorders often receive less research funding than more high profile threats, the sheer number of rare disorders – over 7,000 – accelerates the race for answers.

“If you add them all up, an estimated 25 million people in the United States are affected by rare disorders, and another 35 million in Europe,” Soucie says. “So if you can learn about the genetic mutations, you can shape innovations that potentially will affect many more people. The implication for public health is huge.”

Shannon Easley is associate vice president for communications with the CDC Foundation