CHS Research Grants for 2005

The bleeding tendency of people with severe hemophilia varies considerably. This can be explained by differences in levels of their deficient proteins (clotting factor VIII or IX) which are too small to be easily measurable. We think that an additional source of variability could lie in fibrinolysis, the process by which blood clots dissolve. Severe hemophilia patients who have rapid fibrinolysis (clots that dissolve quickly) might tend to bleed more severely than others. In this project, we propose to conduct a thorough and systematic study to test the hypothesis that the bleeding tendency in severe hemophilia is correlated with increased fibrinolytic activity. We will measure the levels of four key blood proteins which contribute to fibrinolysis in 100 severe hemophilia patients. We will also monitor the number of bleeding episodes as well as the amount of factor VIII or IX concentrate that these patients have needed over the preceding 2 years. We will statistically determine whether increased values of the fibrinolytic proteins correlate with increased bleeding tendency, and vice versa. At the end of this project, we hope to better our understanding of why bleeding tendencies in severe hemophilia patients are variable. If our hypothesis is confirmed, we will be able to provide a novel rationale for individualized management approaches. These may include selecting target amount of factor VIII or IX for treatment or prevention of bleeding in hemophilia patients. It may also include selecting patients for prophylaxis with clotting factor concurrently with factor VIII or IX replacement therapy, after surgery and other interventions. We may also be able to predict the risk of clotting of central venous catheters, a serious complication of propylactic factor VIII or IX treatment in young children.