Our work will focus on developing evidence as to whether or not there is allotypy of the Factor VIII molecule in the human population. This will be pursued in the following three ways: (1) Precise quantitative assay of the potency of inhibitor antibodies from two or three different hemophilic patients will be obtained using a panel of Factor VIII donors; the hypothesis here is that the antibody will exhibit a higher titer against a Factor VIII source which coincides closely to the antigenic specificity of that antibody than it will against a Factor VIII source having significantly different determinants. (2) A specific quantitative assay for Factor VIII cross- reacting material (VIII-CRM), based on rabbit antibody neutralization which is in the final developmental stages, will be similarly applied to a variety of normal, hemophilic, and von Willebrand's subjects' plasmas in order to detect differences in antigenic determinants. (3) Attempts will be made to convert the non-precipitating human antibody-Factor VIII complex to a precipitating reaction, starting with the hypothesis that it is the large size of normal polymeric Factor VIII which imposes steric hindrance on lattice formation. Thus we have begun work with small molecular weight Factor VIII monomers with a view to using a quantified precipitin reaction as another index of similarity or difference in antigenicity. Other projects include: measures to neutralize the thrombin which contaminates some lots of commercial, therapeutic prothrombin complex concentrates by preincubation of the preparation with plasma (for its antithrombin content) and heparin; and development of techniques for detection of early thrombus formation in coronary vessels by study of coronary sinus samples drawn through catheters in patients being studied as candidates for coronary bypass surgery.