Senior Investigator Alan Mast, MD, PhD, is studying tissue factor pathway inhibitor (TFPI) and its impact on patients with bleeding and clotting disorders.
More than 3 million people across the United States are affected by bleeding disorders like hemophilia and von Willebrand disease. These patients’ blood doesn’t clot the way it should, which can cause greater health risks. Versiti Blood Research Institute Senior Investigator and Medical Director of Transfusion Medicine Alan Mast, MD, PhD, is hard at work researching the basic science of blood coagulation, hemostasis and thrombosis, and vascular biology, with the hope of developing new treatments for patients with bleeding and clotting disorders.
When you cut yourself and start to bleed, your blood comes in contact with tissues in your body. Tissue factor (TF), a protein found in the body’s tissues (but not in blood), helps your blood to clot and a scab to form. Tissue factor pathway inhibitor (TFPI) controls this TF-initiated process. It is the only protein found in the human body that inhibits the function of TF. Therefore, TFPI acts as an anticoagulant, making it difficult for blood to clot. In patients with hemophilia who lack Factor VIII or Factor IX, TFPI makes the clotting process even more difficult to initiate.
Patients with hemophilia are often treated with intravenous FVIII or Factor IX replacement proteins. Researchers like Dr. Mast are interested in learning more about blood clotting in an effort to develop other treatment options. TFPI is a therapeutic target protein for treatment of patients with hemophilia, since drugs that block TFPI make them bleed less. These new drugs could reduce the need for regular intravenous infusions and could be administered under the skin by the patient him- or herself.
Along the way, researchers have found that TFPI, an anticoagulant, and Factor V, a clotting protein found in blood, each contain a small portion of amino acid sequence that is the same within both proteins. Researchers are trying to understand the role this amino acid sequence plays in the functions of the two proteins. Dr. Mast and his laboratory team at Versiti Blood Research Institute are at the forefront of this research. They discovered that TFPI binds to activated Factor V (FVa). When these two factors bind together, TFPI controls how FVa promotes clot formation. Factor V Leiden, the most common pro-coagulant in Caucasians, is resistant to inhibition by TFPI, producing a lower threshold for formation of a blood clot. The more that investigators like Dr. Mast understand TFPI and how it interacts with coagulation proteins, the better they will understand blood clotting, allowing the development of new, more effective treatments for patients with bleeding and clotting disorders.
About the expert: Alan Mast, MD, PhD, is the medical director of transfusion medicine and senior investigator at Versiti Blood Research Institute.