Immunologic Evidence That the Antihemophilic Factor ( Factor VIH ) - like Material in Hemophilic Plasma Possesses a Nonfunctional Low

Antihemophilic factor (AHF, factor VIII) is a macromolecule that can be dissociated into two subcomponents. One, of high molecular weight (MW), forms precipitates with heterologous antiserum against AHF and supports ristocetin-induced aggregation of platelets. The other, of lower MW, has procoagulant activity. The plasma of patients with classic hemophilia contains a form of AHF with properties resembling those of the high MW subcomponent. Studies of Hoyer and Breckenridge have suggested that the low MW subcomponent is present in a minority of patients whose plasmas inhibit human “circulating anticoagulant” anti bodies against AHF. The present studies provide further evidence that such individuals, said to be CRM+, have a species of AHF possessing a nonfunctional variant of the low MW subcomponent. CRM+ hemophilic plasma or serum, like the low MW subcomponent of normal AHF, blocked the inhibitory properties of circulating anticoagulants, in contrast to the high MW subcomponent of normal AHF. A nonfunctional low MW subcomponent has been identified in partially purified AHFlike material separated from the plasmas of both CRM+ and CRMhemophiliacs, the latter being patients whose plasmas do not neutralize circulating anticoagulants. This low MW subcomponent, like that of normal AHF, inhibited antiserum against the normal low MW subcomponent, but not antiserum against the normal high MW subcomponent. Thus, the defect in the hemophilic plasmas tested was not associated with the absence of the low MW subcomponent of AHF.