MULTIMERIC COMPOSITION OF FACTOR-VIII VONWILLEBRAND-FACTOR FOLLOWING ADMINISTRATION OF DDAVP - IMPLICATIONS FOR PATHO-PHYSIOLOGY AND THERAPY OF VONWILLEBRANDS DISEASE SUBTYPES

Abstract

The modifications in the multimeric composition of plasma factor VIII/von Willebrand factor and the breeding time response following administration of 1-deamino-[8-D-arginine]-vasopressin (DDAVP) to patients with different subtypes of von Willebrand''s disease were studied. In type I, all multimers were present in plasma in the resting state, though they were decreased in concentration. Administration of DDAVP resulted in an increased concentration of these forms as well as the appearance of larger forms than were previously present. There was concomitant correction of the bleeding time. In type IIA, large multimers were absent in the resting state, and although DDAVP induced an average 3-fold increase in the plasma concentration of factor VIII/von Willebrand factor, the larger multimers did not appear and the bleeding time, although shortened, was not corrected. The larger multimers that were also absent from type IIB plasma in the resting state rapidly appeared following DDAVP administration. Their appearance was transitory and the bleeding time, as in IIA patients, was shortened but not corrected. The characteristic multimeric composition of platelet factor VIII/von Willebrand factor in given subtypes predicted the alteration in plasma factor VIII/von Willebrand factor induced by DDAVP. The different subtypes of von Willebrand''s disease apparently represent distinct abnormalities of factor VIII/von Willbrand factor. Complete hemostatic correction following DDAVP can be routinely expected only in type I von Willebrand''s disease, and only if factor VII/von Willebrand factor can be raised to normal levels.