Grant: Project Grant

Clotting factors are proteins found in the blood that react to blood vessel damage to form a clot and prevent blood loss. If these clotting factors are not present or are defective, bleeding can occur. Severe hemophilia B (HB) is a bleeding disorder caused by insufficient activity of factor IX (FIX) and it is characterized by recurrent spontaneous bleeding, mainly in the joints and muscles. Replacement of the missing clotting factor (FIX) requires intravenous injections 2-3 times a week to maintain optimal levels in the blood. However, blood levels of FIX do not always predict bleeding risk as accurately as blood levels of other clotting factors. FIX is a unique clotting factor because it has been found to localize in the various organs and tissues of the body where it binds to collagen, a very common protein in the connective tissue that supports the structure of the skin, tendon, vessels, muscle, and other organs and tissues. We have obtained preliminary data showing that this specific localization of FIX could be important for the prevention of bleeding in HB patients. This might be relevant for the treatment of HB patients, especially now that there are several new FIX products available for the treatment of hemophilia. Some of these have been modified in a way that prevents them to migrate to the extravascular space, thus losing the ability to bind collagen. This study aims to investigate the function of FIX in the tissues to improve the therapeutic management of hemophilia B patients.