Correction by factor VIII of the impaired platelet adhesion to subendothelium in von Willebrand disease

Abstract

The interaction of platelets with subendothelium has been studied by circulating citrated blood at arterial shear rates through a chamber containing everted segments of rabbit aorta from which the endothelium has been previously removed by balloon catheter. Using this technique, impaired platelet adhesion to subendothelium has been described in patients with von Willebrand disease. The defect was more striking if the vessel segments had been digested with α-chymotrypsin, producing a surface whose platelet reactivity was due primarily to fibrillar collagen. In order to determine whether this defect in platelet adhesion could be corrected by factor VIII, studies were performed in six patients with von Willebrand disease. Cryoprecipitate was chromatographed on Bio-gel A-15m and the following fractions were collected: early-eluting fractions (column buffer), void-volume fractions (factor VIII), and late-el uting fractions which contained the peak absorbance at 280 nm but were devoid of factor VIII activity (“albumin” control). For each of the six patients, perfusion studies were performed on five aliquots of citrated blood to which had been added (1) nothing, (2) column buffer 1,(3) factor VIII, (4) albumin control, or (5) column buffer 2. Adhesion (percent surface coverage) of platelets to α-chymotrypsin digested segments was determined by a morphometry technique. Adhesion values (percent adhesion ± SE) were as follows: (1)8.2 ± 1.1, (2) 9.8 ± 1.5, (3) 24.7 ± 2.9, (4) 12.5 ± 1.8, and (5) 10.3 ± 1.8 (normal values 28.2 ± 2.1). The corrective effect of factor VIII was more striking in the three patients with the lowest levels of the factor VIII complex. In one patient, platelet adhesion was corrected after transfusion of cryoprecipitate. The finding that factor VIII is required for the adhesion of platelets to subendothelium may be relevant to both hemostasis and to the pathogenesis of atherosclerosis.