Ddavp-Induced Alterations In The Multimeric Composition Of Factor Viii/Von Willebrand Factor In Normal And Von Willebrand’S Disease Plasma
DDAVP is known to induce increases in plasma FVIII/von Willebrand Factor (FVIII/vWF) concentration by release of tissue stores. We have now found that the multimeric composition of plasma FVIII/vWF alters following DDAVP administration to resemble that seen in platelets. Multimers were resolved by thin-layer SDS-agarose and SDS-agarose acrylamide electrophoresis and were identified by reaction of the fixed gels with 125I-laben ej antibody followed by autoradiography. Fifteen minutes after DDAVP infusion, larger multimers appeared in normal plasma than were present during the resting state. These larger multimers were also present in resting normal platelets, suggesting that DDAVP causes their release from tissue stores. In Type I von Willebrand s disease (vWd), there is a decreased quantity of circulating FVIII/vWF but the multi meric composition is normal in plasma and platelets. The response to DDAVP was qualitatively similar to that in normal individuals. In Type IIA vWd large multimers are absent both from plasma and platelets. Even though DDAVP induced a threefold rise in FVIII/vWF plasma concentration, these large forms did not appear. In 11B vWd only intermediate and small multimers are present in plasma but there is a normal complement of multimers in platelets. Following DDAVP there was a rapid correction of the plasma multimeric composition so that it was identical with the pattern seen in normals after DDAVP. However, this correction was transitory and the abnormal basal pattern soon reappeared. These disparate changes in plasma FVIII/vWF multimeric composition following DDAVP suggest that platelet FVIII/vWF is representative of releasable tissue stores. They also provide insight into the variable hemostatic response to this agent and suggest different pathogenic mechanisms for the vWa subtypes.