Human blood platelet adhesion to artery subendothelium is mediated by factor VIII–Von Willebrand factor bound to the subendothelium

Abstract

ONE of the early events in the haemostatic process is the adherence of blood platelets to collagen of the subendothelium. Subsequent platelet-to-platelet adhesion then leads to the formation of a haemostatic plug. The role of a plasma factor in this process was recognised after the discovery^1,2 that the prolonged bleeding time of patients with Von Willebrand disease could be corrected by transfusion of plasma or cryoprecipitate. This plasma factor, then named Von Willebrand factor, was later identified as factor VIII (anti-haemophilic factor A (ref. 3)). The current concept is that Von Willebrand factor and factor VIII are present in a complex, which can be dissociated in certain conditions. Despite this progress, little is yet known about the role of the factor VIII-Von Willebrand factor complex (factor VIII–VWF) in the haemostatic plug formation. Tschoppet al. showed that the Von Willebrand factor was required for normal adhesion of platelets to rabbit subendothelium in a perfusion chamber using blood from patients with Von Willebrand disease⁴. The role of factor VIII–VWF in platelet adhesion is also important for the development of atherosclerosis. In this process, adherence of platelets is followed by degranulation and concomitant secretion of factors causing intimai migration and proliferation of smooth muscle cells^5,6. Defective adherence of platelets was shown to protect against experimental atherosclerosis^7,8. We present here evidence that factor VIII–VWF binds to subendothelium of human arteries and that subendothelium-bound factor VIII–VWF mediates the platelet adhesion.