Hemophilia A and B are hereditary bleeding disorders caused by deficiencies in factor VIII (FVIII) and factor IX (FIX), respectively. Hemophilia is often treated with replacement factors (ex. recombinant or plasma-derived FVIII or FIX), or bypassing agents (ex. recombinant activated factor VIIa, anti-inhibitor coagulation complex, or recombinant porcine FVIII). We have shown effects of novel hemostatic agents on fibrin formation, structure, and stability, including recombinant factor VIIa (NovoSeven) (Wolberg et al, Allen et al, Gray et al) and factor XIII. We are continuing these investigations to understand how replacement and bypassing therapies modify fibrin quality, and identify new, improved drugs to reduce bleeding in persons with hemophilia.