Platelet Activation in Flowing Blood Passing Growing Arterial Thrombi

Abstract

We investigated the combined effect of wall shear rate and immobilized collagen on platelet activation in flowing nonanticoagulated human blood. By combining an ex vivo model of thrombogenesis with flow cytometry, we showed that activated platelets can be detected in the bloodstream passing growing thrombi at a wall shear rate characteristic of moderately stenosed arteries (2600 s-1). The activation of the circulating platelets was clearly correlated with thrombus growth. Different antibodies against platelet activation-dependent surface markers had distinct sensitivity to the thrombotic process. alpha-Granule release detected by surface expression of CD62P seemed to be the most sensitive marker, as judged by both mean fluorescence intensity and fraction of platelets activated. The conformational change in glycoprotein IIb-IIIa, as detected by PAC-1, also seemed to be a sensitive marker and preceded binding of fibrinogen to activated glycoprotein IIb-IIIa, as detected by anti-fibrinogen. Large thrombi also elicited lysosome exocytosis, detected by surface expression of CD63. Finally, we observed a small decrease of glycoprotein Ib-IX expression, as detected by anti-CD42a. Thus, our study provides further information on the dynamics of platelet activation in relation to thrombus growth at arterial shear conditions in flowing nonanticoagulated human blood.

Cardiopulmonary Bypass Induces Release of Soluble CD40 Ligand

“…Given that platelet counts average 2.5ϫ10 8 platelets/mL, sufficient platelet-associated CD40L is available to account for the Ϸ1 ng/mL sCD40L observed in plasma after CPB. Second, the stimulation of platelets that occurred during CPB, typically monitored either by quantification of ␣-granule proteins in plasma (eg, PF4 and ␤-TG) 24 or activation markers on circulating platelets (eg, P-selectin, CD63, or activated GP IIb/IIIa), 26,27 provides a mechanism for the release of sCD40L. The patient cohort examined herein also showed procedurally induced platelet stimulation, as detected by a rise in plasma PF4 and ␤-TG.…”

Association between arterial stiffness and platelet activation

“…In such patients, platelets are activated at the site of atheroma 1 due to increased shear stress in the narrowed vessels. 2,3 Increased platelet activation is observed in patients with coronary risk factors and cardiovascular events. [4][5][6][7][8][9][10][11][12] Increased arterial stiffness, measured with pulse wave velocity (PWV), has been shown to be associated with atherosclerosis and risk factors of atherosclerotic cardiovascular disease, [13][14][15][16][17][18][19][20][21] and is an independent predictor of cardiovascular events, 22,23 Therefore, although platelets are likely to be activated in patients with atherosclerotic disease who exhibit increased arterial stiffness, little is known about the relation of arterial stiffness itself to platelet activation.…”

“…On the other hand, platelet activation can be detected directly by measuring surface antigen CD62P using flow cytometry. 2,3,5,9,10,12 Furthermore, detection of platelet-neutrophil complexes (PNC), which are formed as a result of interaction with CD62P provides an additional means to detect platelet activation. 24 The purpose of this study was to investigate the association between arterial stiffness and platelet activation by measuring PWV, P-selectin, and PNC in subjects without atherosclerotic disease.…”

Platelet Activation During Carotid Endarterectomy And the Antiplatelet effect of Dextran 40

“…5 Platelet activation has also been shown in flowing blood passing growing arterial thrombi using a combined effect of wall shear rate and immobilised collagen in an experimental model. 6 Thrombin, a potent platelet activator and procoagulant agent has been shown to be generated during CEA despite the use of unfractionated heparin. 7 This effect can persist perioperatively as thrombin is able to bind to the injured vessel wall.…”