Shear-induced platelet aggregation requires von Willebrand factor and platelet membrane glycoproteins Ib and IIb-IIIa

Abstract

Different types of platelets in various types of plasma were subjected to levels of shear stress that produce irreversible platelet aggregation in normal platelet-rich plasma (PRP). At shear stresses of 90 or 180 dyne/cm2 applied for 30 seconds or five minutes, aggregation was either absent or only transient and reversible using severe von Willebrand's disease (vWD) PRP (less than 1% von Willebrand factor, vWF); Bernard-Soulier syndrome (BSS) PRP (platelets deficient in the membrane glycoprotein Ib, GPIb); normal PRP plus monoclonal antibody (MoAb) to GPIb; thrombasthenic PRP (platelets deficient in membrane glycoprotein IIb-IIIa complex, GPIIb-IIIa); and normal PRP plus MoAb to GPIIb-IIIa. Shear-induced aggregation was inhibited under the above conditions, even though the platelets were activated to release their granular contents. Sheared normal platelets in vWD plasma aggregated in response to added vWF. These studies demonstrate that the formation of stable platelet aggregates under conditions of high shear requires vWF and the availability of both GPIb and GPIIb-IIIa on platelet membranes. The experiments demonstrate that vWF-platelet interactions can occur in the absence of artificial agonists or chemical modification of vWF. They suggest a possible mechanism for platelet aggregation in stenosed or partially obstructed arterial vessels in which the platelets are subjected to relatively high levels of shear stress.

1‐deamino‐8‐D‐arginine vasopressin (DCAVP) increases platelet membrane expression of glycoprotein Ib in patients with disorders of platelet function and after cardiopulmonary bypass

“…The functional implications of these two findings are unclear. Increases in platelet membrane GPIb could potentially be associated with improved platelet adhesion because of the importance of this glycoprotein in mediating adhesion at high shear rate [43]. However, although platelets lacking GPIb have significant defects in platelet adhesiveness [44], no clinical data exist to relate quantitative GPIb expression to platelet adhesiveness.…”

Platelet activation mechanisms and markers in arterial thrombosis

“…Shear stresses of 50 dynes cm −# or higher trigger platelet activation, cause release of granules and induce platelet aggregation [7,32]. Shear stress of this magnitude occurs at arteries partly occluded by atherosclerosis and around artificial valves and circulation-assistant devices.…”

“…# 1996 Blackwell Science Ltd Journal of Internal Medicine 239 :[17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] …”

A V740L mutation in glycoprotein IIb defines a novel epitope (War) associated with fetomaternal alloimmune thrombocytopenia

“…This protein is a receptor for fibrinogen, von Willebrand factor, and other ligands and is essential to initiating PLT activation and ultimately clot formation. 11,12 The essential role of GPIIb/IIIa in maintaining hemostasis is highlighted in cases of Glanzmann's thrombasthenia where the absence or reduced expression of GPIIb/IIIa leads to a lifelong tendency of mucosal bleeding. 13,14 GPIIb/IIIa is a heterodimeric integrin consisting of the GPIIb (aIIb) encoded by the ITGA2B gene and the GPIIIa (b3) encoded by the ITGB3 gene.…”