International collaboration aims to predict life-threatening reaction to heparin treatment

TUCSON, Ariz. – Each year, as many as 12 million hospitalized patients — one-third of all individuals hospitalized — are prescribed the anticoagulant medication, heparin.

Of those patients, as many as 2.4 percent will develop an adverse reaction to the drug, known as heparin-induced thrombocytopenia, a condition that has a greater than 30 percent mortality rate and can result in catastrophic, life-threatening complications, including thrombosis, the abnormal formation of blood clots in a blood vessel.

Thrombocytopenia is a deficiency of blood platelets, the cells that help blood clot. It occurs as a result of a separate disorder, such as an immune system problem, or it can be a side effect of taking certain medications, like heparin.

Despite the high mortality and serious complications, no tests exist to evaluate heparin-induced thrombocytopenia (HIT) risk before administering the medication. Furthermore, a knowledge gap exists regarding the molecular and cellular mechanisms of the condition.

To address this problem, Jason Karnes, PharmD, PhD, assistant professor in the UA College of Pharmacy, received a five-year, $769,000 K01 career development award from the National Institutes of Health to identify predictive and early diagnostic biomarkers for HIT. This research also will help develop effective, personalized preventive and therapeutic interventions.

“New clinical tools are needed to predict heparin-induced thrombocytopenia,” Dr. Karnes said. “If we could determine patients who may be predisposed to the condition, we could enable clinicians to avoid heparin in at-risk patients, monitor patients at high-risk and prevent complications or death related to the condition.”

The study will begin by examining samples from more than 5,000 international patients. The goal is to identify genetic predictors of individuals who have experienced HIT. The second phase will enroll 100 patients and identify RNA signatures — or gene expressions — that might signal the development of this condition. These RNA signatures then could be used to better understand HIT and develop early diagnostic tools.

“An understanding of heparin-induced thrombocytopenia genetic risk profiles may have broad-ranging implications for pathophysiology and treatment, as well as future research focusing on novel therapeutic targets,” Dr. Karnes said.

K01 career development awards support junior research scientists seeking both advanced research training and additional experience in specific areas of expertise. This is the first K01 award received by a faculty member in the College’s Department of Pharmacy Practice and Science. Dr. Karnes will be mentored by Joe G.N. “Skip” Garcia, MD, professor of medicine and physiology at the UA College of Medicine – Tucson, professor of pharmacology and toxicology at the UA College of Pharmacy and a professor with the UA BIO5 Institute.

“With the support of our laboratory and mentorship from expert clinicians, Dr. Karnes has facilitated an international collaboration aimed at identifying genomic predictors of this condition,” Dr. Garcia said. “Preliminary data from this collaboration serves as the basis of the research and constitutes some of the most exciting recent work in heparin-induced thrombocytopenia.”

The research team includes other UA faculty members as well as colleagues at other institutions, including Yves Lussier, MD, professor of medicine, associate vice president for data science for UA Health Sciences, director of the Center for Biomedical Informatics and Biostatistics, and director of informatics for the UA BIO5 Institute; Nancy Sweitzer, MD, PhD, professor of medicine and director of UA Sarver Heart Center; Jeff Frelinger, MD, PhD, professor of immunobiology, UA College of Medicine – Tucson and Dan Roden, MD, senior vice president for personalized medicine at Vanderbilt University Medical Center.

Research reported in this news release is supported by the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award No. K01HL143137. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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