Hemophilias A and B (deficiency in factors VIII or IX) are hereditary bleeding disorders. We are examining how these deficiencies modulate thrombin generation, and clot formation, structure and stability. We have observed that hemophilia causes the formation of clots with an abnormal structure that are weak and poorly formed, and have decreased stability in the presence of fibrinolytic enzymes. We hypothesize that hemophilic bleeding results from formation of poorly structured clots and that therapies that stop bleeding do so by normalizing clot structure and stability. We are comparing different strategies to treat hemophilic bleeding, including replacement therapy and bypass therapy with high dose factor VIIa, FEIBA, or novel bioengineered “superenzymes.”