Hiroyuki Sakai

Enhanced Shear-Induced Platelet Aggregation in Acute Myocardial Infarction

BACKGROUND Experiments under controlled flow conditions indicate that the binding of von Willebrand factor (vWF) to platelet glycoprotein (GP) Ibalpha and integrin alphaIIbbeta3 (GP IIb/IIIa complex) is crucial for aggregation at elevated shear rates. We have tested how the plasma of patients with acute myocardial infarction affects this process. METHODS AND RESULTS Citrated plasma was obtained from 18 patients with acute myocardial infarction within 6 hours from the onset of symptoms and from 26 control subjects with chest pain syndrome without evidence of ischemia. Aggregation of normal platelets at high shear rates was significantly greater in the presence of patient than control plasma and was inhibited by both anti-GP Ibalpha and anti-alphaIIbbeta3 monoclonal antibodies. The observed values (mean+/-SD) were 47.6+/-17.8% versus 30.1+/-9.9% at 10 800 s-1 (P<0.01) and 32.9+/-14.1% versus 17.5+/-9.5% at 7200 s-1 (P<0.01), respectively, and were positively correlated with plasma vWF antigen levels and ristocetin cofactor activities. In contrast, at the lower shear rate of 1200 s-1, aggregation was similar in the presence of control or patient plasma and was not inhibited by the anti-GP Ibalpha antibody. Both vWF antigen and platelet aggregation decreased 2 weeks after the onset of myocardial infarction. CONCLUSIONS Shear-induced platelet aggregation is enhanced in plasma in the presence of acute myocardial infarction, apparently as a result of increased vWF concentration. This may contribute to the onset of acute coronary artery thrombosis and early reocclusion after reperfusion treatment.

Functional compensation of the low platelet count by increased individual platelet size in a patient with May-Hegglin anomaly presenting with acute myocardial infarction

Platelets are known to play a crucial role in normal hemostasis as well as in thrombus formation at sites exposed to blood flow, as in coronary thrombosis. Thus, low platelet count is a strong negative risk factor for the occurrence of arterial thrombosis, such as occurs in acute myocardial infarction. We encountered a patient with May-Hegglin anomaly, presenting with acute myocardial infarction in his sixth decade, even though his platelet counts had always been less than 50 x 10(3)/microl. We investigated the characteristics of his platelets under the effect of shearing and found that shear-induced platelet aggregation and binding of soluble von Willebrand factor (vWF) to platelets could be induced, even when the patients platelet count was less than 10 x 10(3)/microl, but that virtually no aggregation or vWF binding by normal platelets could be induced by shearing when platelet counts were less than 50 x 10(3)/microl. We conclude that the low platelet counts in a patient with May-Hegglin anomaly can be functionally compensated for by larger individual platelets, in view of the vWF-dependent platelet thrombus formation occurring under the effect of blood flow and that that is why most patients with May-Hegglin anomaly do not have a bleeding tendency, even though their platelet counts are very low.

Enhanced Shear-induced von Willebrand Factor Binding to Platelets in Acute Myocardial Infarction

Recent investigations have suggested that von Willebrand factor (vWF) plays a crucial role in platelet thrombosis under flow conditions. The effects of plasma obtained from 15 patients with acute myocardial infarction and 10 patients with the chest pain syndrome as controls, on shear-induced vWF binding to platelets and subsequent platelet activation, as evidenced by microparticle release, were investigated by quantitative flow cytometry. Platelet-rich plasma was obtained from a 38-year-old healthy male volunteer with blood type O. Stored plasma from either the acute myocardial infarction or control patients was then added to the freshly prepared platelet-rich plasma in equal volumes. The mixtures were then exposed to specific shear rates in an optically modified cone-plate viscometer. The number of vWF molecules bound to the platelet surface and the number of microparticles released from the platelets were then measured by quantitative flow cytometry using an FITC-conjugated anti-vWF monoclonal antibody. The shear-induced increase in vWF binding to the platelet surface was enhanced in the presence of plasma from patients with acute myocardial infarction (acute myocardial infarction plasma). The shear-induced release of microparticles from platelets was enhanced from 889+/-134 in the presence of control plasma to 1045+/-222 in the presence of the acute myocardial infarction plasma (p<0.05). Acute myocardial infarction plasma also reduced the shear rate threshold required to induce measurable shear-induced vWF binding from 10800 s(-1) to 9000 s(-1). We conclude that the plasma of acute myocardial infarction patients contains factors that enhance shear-induced vWF binding and vWF-mediated platelet activation, which may contribute to thrombotic re-occlusions of the coronary arteries in patients who have received reperfusion treatments.