Inhibition of von Willebrand factor-platelet interaction by fibrinogen.
The prolonged bleeding time and frequent haemorrhagic episodes in patients with severe von Willebrand's disease (vWD) attest to the importance of von Willebrand factor (vWF) in platelet adhesive functions. In in vitro systems, vWF is directly involved in platelet adhesion at high shear rates, and this participation may be mediated by platelet receptors for vWF. Two apparently distinct mechanisms have now been identified for enhancing 125I-vWF interaction with stimulated platelets: one is induced by ristocetin and apparently mediated by platelet membrane glycoprotein Ib (GPIb); a second mechanism has been identified more recently and is induced by the physiological stimuli ADP and thrombin. The failure of thrombin to support 125I-vWF binding to thrombasthenic platelets, which contain GPIb but lack GPIIb/IIIa, suggests that the mechanism of this interaction may be distinct from ristocetin-induced binding. As ADP and thrombin are released at sites of platelet accumulation, it is possible that these agonists regulate the vWF-platelet interactions in vivo. To test this hypothesis, we have examined ADP- and thrombin-supported 125I-vWF binding to platelets in the plasma of severe vWD patients, and report here that it is inhibited by fibrinogen. Thus, in addition to its role in coagulation and platelet aggregation, fibrinogen influences the binding of vWF to thrombin- and ADP-stimulated platelets.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000527:Alprostadil; D001779:Blood Coagulation Factors / Q000502:physiology*; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D005340:Fibrinogen / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D010980:Platelet Membrane Glycoproteins; D011458:Prostaglandins E / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000502:physiology; D013917:Thrombin / Q000502:physiology; D014841:von Willebrand Factor / Q000502:physiology*
D001779:Blood Coagulation Factors; D010980:Platelet Membrane Glycoproteins; D011458:Prostaglandins E; D011956:Receptors, Cell Surface; D014841:von Willebrand Factor; C028254:von Willebrand factor receptor; D000244:Adenosine Diphosphate; D005340:Fibrinogen; D013917:Thrombin; D000527:Alprostadil