Patients with thrombotic thrombocytopenic purpura that is refractory to conventional fresh frozen plasma (FFP) exchange therapy are sometimes switched to cryosupernatant as the replacement fluid, although its hemostatic properties are not well defined. We performed several key coagulation assays on three pools of four units from each of three ABO groups of cryosupernatant and FFP. Fibrinogen, factor VIII activity, and von Willebrand factor antigen (vWF:Ag) levels were all significantly lower in cryosupernatant compared with FFP, although at levels usually not considered clinically significant. We confirmed that group O FFP contained significantly less factor VIII activity and vWF:Ag compared with groups AB and B. In contrast to FFP, group AB cryosupernatant contained lower levels of fibrinogen, factor V activity, factor VIII activity, and vWF:Ag than groups O or B. Group AB cryosupernatant, with the lowest levels of vWF:Ag and universal ABO compatibility, may be the product of choice for refractory thrombotic thrombocytopenic purpura.