September 26, 2013
Heparin is a widely used blood thinner given to patients to prevent blood clots. However, the drug is sometimes its own worst enemy, as some of its components can cause the very thing it is supposed to stop.
Jian Liu, PhD, a professor at the UNC Eshelman School of Pharmacy, has received a grant to help the Food and Drug Administration sniff out those potentially dangerous components in heparin. Liu says the research could help improve the drug’s safety, which has been a hot-button issue since a contaminated supply of heparin caused more than eighty deaths and hundreds of adverse reactions in 2008.
“The FDA is paying a lot of attention to heparin because of its safety issues,” Liu says. “The research supported by this grant could help modernize the quality control of heparin and improve its safety.”
Identifying the Culprits
Natural heparin, which is extracted from animal tissues, is a mixture of compounds. Not all of these components have anticoagulant properties. Some of them—it is not known which ones—could even trigger the opposite effect and cause heparin-induced thrombocytopenia, where the body develops an immune response to the drug and produces blood clots through a mechanism different from the one that heparin is designed to stop. About 0.2 to 5 percent of patients receiving heparin for more than four days develop HIT. The condition can be life-threatening and often leads to amputations.
Liu’s FDA grant will provide up to $1.2 million over five years to support efforts to identify structural components of heparin that are likely to cause HIT. Liu will tackle the task with two collaborators.
- Liu’s lab will chemically synthesize individual molecules of heparin fragments with defined structures.
- Robert Lindhardt, PhD, a Senior Constellation Professor at Rensselaer Polytechnic Institute, will verify the structures of those fragments.
- Gow Arepally, MD, an associate professor of medicine and pathology at Duke University, will test whether those heparin fragments cause HIT.
Screening for the Culprits
Once the FDA knows which components might cause HIT, it needs to be able to screen for their concentrations in heparin mixtures. That is difficult to do, Liu says, because the components of a natural heparin mixture cannot be easily disentangled and measured.
“It’s like if you mixed Tylenol and aspirin, it would be very hard to tell which part of that mixture comes from Tylenol and which part comes from aspirin,” Liu says. “When you’re dealing with a mixture, you can only determine an average structure.”
Liu says this project could provide a tool to paint a more precise picture of the makeup of heparin mixtures. The heparin fragments created by his lab will carry distinct molecular fingerprints. The FDA could use those fragments as references and look for those fingerprints in a heparin mixture.
“If you see a specific fingerprint, then you know it’s coming from a particular fragment,” Liu says. “Potentially, these references will help the FDA determine what percentage of a heparin compound is made up of which fragment.”
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