Versiti Blood Research Institute Articles
Exploring the Causes of Heparin-Induced Thrombocytopenia
Investigator Renren Wen, PhD, is digging deeper into HIT to better understand why some patients, after heparin treatment, experience a drop in platelet counts, which is sometimes accompanied by life-threatening thrombosis.
Oftentimes, to prevent clots or treat them after they develop, patients are treated with the blood thinner heparin, an effective and relatively low-cost medication that controls coagulation. But an estimated 30-50% of patients who take heparin can develop antibodies to the drug, with some experiencing adverse reactions that could lead to irreversible damage or loss of life.
Some patients develop heparin-induced thrombocytopenia (HIT), a reaction to heparin treatment that occurs when an individual develops an antibody response to a complex formed between heparin and the platelet protein PF4 (PF4/H complex) that causes their platelet count to drop and, paradoxically, blood to coagulate. Patients diagnosed with HIT are typically taken off heparin immediately and are prescribed other anticoagulants. But these alternative medications are much more costly and can sometimes cause patients to experience even worse side effects, including life-threatening bleeding. Versiti Blood Research Institute Investigator Renren Wen, PhD, is digging deeper into HIT to understand what causes it and why, with a goal of finding better diagnosis and treatment options.
Whereas a high percent of patients treated with heparin develop antibodies to PF4/H complex, only a subset of such patients develop HIT. Dr. Wen believes that B cells are the key to understanding why some patients develop HIT and others do not. B cells are an essential part of the body’s immune system that can react to antigens by generating antibodies. It has been thought that there are at least two types of PF4/H-binding antibodies – those that can activate platelets and are thus called “pathogenic” antibodies, and those that cannot activate platelets and are thus called “non-pathogenic” antibodies. To understand the difference between the “pathogenic” and “non-pathogenic” antibodies, Dr. Wen and her group cloned these two types of antibodies from HIT patients and observed that the “pathogenic” antibodies have structural signatures that distinguish them from the “non-pathogenic” ones.
Dr. Wen believes that the cloned “pathogenic” antibodies and the associated structural signatures can be used to facilitate better understanding of the molecular pathogenesis of HIT and to develop novel diagnosis and treatment for HIT. “This could have the potential for better diagnosis and treatment of HIT,” she said.
Dr. Wen often collaborates with other investigators who research HIT and treat patients with the disease, which helps propel lifesaving discoveries. “Versiti Blood Research Institute is a positive environment where people talk to each other and work together toward a common goal,” she said.