Platelet adherence

Dismption of the endothehal surface of blood vessels expose coUagen fibers and connective tissue. These provide surfaces that promote platelet adherence, platelet release reaction, and subsequent platelet aggregation. Substances Hberated from the platelets stimulate further platelet aggregation, eg, adenosine diphosphate maintain vasoconstriction, eg, serotonin and participate in blood coagulation, eg, platelet Factors III and IV. In addition, the release reaction modifies platelet membranes in a manner that renders phosphoHpid available for coagulation. The thrombin [9002-04-4] elaborated by the coagulation mechanism is a potent agent in the induction of the platelet release reaction. 

Platelets adherent to collagen change shape and spread out on the subendothelium. They release the contents of their storage granules (the dense granules and the alpha granules) secretion is also stimulated by thrombin. 

O The cause of an acute coronary syndrome is the rupture of an atherosclerotic plaque with subsequent platelet adherence, activation, and aggregation, and the activation of the clotting cascade. Ultimately, a clot forms composed of fibrin and platelets. 

The rat carotid artery injured by a balloon catheter has been widely used as a model of angioplasty. The rat model is a proliferation model without foam cells (93). This form of injury causes immediate coagulation and thrombosis cascade in which platelets adhere, spread, and degranulate on the denuded surface of the artery, and approximately 24 hours later SMC begin to proliferate. Liposomal BPs, clodronate, and alendronate were injected to male sabra rats, 15 and 3mg/kg, respectively (52,69,76). Marked neointimal formation and decreased luminal area were observed in control animals. Neointima/media (N/M) ratio was 1.3 0.2, and luminal stenosis was 44 3%. LC and LA suppressed intimal growth when administered intravenously on day -1 and day 6. N/M ratios were reduced by 60% and 69% for LC and LA, respectively. 

Physiologically, the maintenance of blood circulating freely in the vascular system reflects a meticulous balance between coagulation and fibrinolysis. After microvascular injury subendothelial structures are exposed to which platelets adhere. This is followed by their aggregation and activation of the coagulation cascade with the ultimate conversion of fibrinogen to fibrin. 

Tumoko and coworkers [485] showed that polymers based on acrylamide, methyl propane sulfonic acid and butyl methacrylate in conjunction with poly(2 methacryloyloxyethyl phosphorylcholine-co-butyl methacrylate) are capable of suppressing platelet adherence. Similar results [486] were found on poly(gamma benzyl 1 glutamate-co-leucine) neutralized with sodium. 

Okano et al. [84] measured changes in cytoplasmic Ca2+ concentrations in platelets adhering to HEMA-STY block copolymer (HSB) surfaces by means of fluorescence microscopy combined with a high performance image processor. Comparative studies were also carried out with the HEMA-STY random (HSR) copolymer of poly HEMA and polystyrene. Their results showed that cytoplasmic free calcium levels in platelets that were in contact with the HEMA-STY... 

Fig. 8. R/Platelet in individual platelets adhering to polymer surfaces. HSB data were statistically confirmed to be different from PSt (P < 0.5), HSR (P < 0.5) and PHEMA (P < 0.5) after 40 s R/Platelet (an index of cytoplasmic free calcium concentration) is the ratio of fluorescence emission intensitie of a Ca2 + indicator dye (Fura 2) loaded in platelets when they are excited at 340 nm and 380 nm. (Reproduced from J Biomed Mater Res [Ref 84 Prevention of changes in platelet cytoplasmic free calcium levels by interaction with 2-hydroxyethyl methacrylate/styrene block copolymer surfaces] through the courtesy of John Wiley Sons, Inc.)...

Rodent KC and HC, as well as human HC, express an inducible NO synthase under septic or inflammatory conditions. In vivo in endotoxemia, this expression is transient. Our in vivo data indicate that this induced -NO serves a protective role in the liver and reduces hepatic injury in endotoxemia. This protective action may be mediated by the capacity of NO to neutralize oxygen radicals and prevent platelet adherence and aggregation. Our in vitro studies show that HC-derived -NO can activate soluble guanylate cyclase. Other in vitro effects include the nonspecific suppression of protein synthesis and a small reduction in mitochondrial aconitase activity. The relevance of these in vitro actions to hepatic function in vivo remains to be determined. 

Modification of the aorta surface with Number of platelets adhered per 1 mm2... 

Quite significant is the fact that the amount of platelets adhered depends on the synthesis procedure for HCP. For example, the platelet adhesion onto silicone rubbers heparinized via the TDMAC procedure was 150000 platelets/cm2, while the very same rubbers that were heparinized via y-aminopropyltriethoxysilane adhered only 90000 platelets/cm2 88). The platelets are to a greater extent adhered by the polymers containing covalently immobilized heparin than by those that elute heparin into the bloodstream n3) although the immobilized heparin itself does not interact with the platelets 21 . 

However, in spite of the significant diversity in the quantitative evaluation of platelet adhesion, the platelets adhered onto heparinized surfaces are neither aggregated nor activated 4-78>. In other words, the intracellular contents of the adhered platelets, which may otherwise contribute to the blood clotting process, is not evolved into the bloodstream. This conclusion is verified by the results of Table 12, which indicate that the increased platelet adhesion does not result in a worse thrombo-resistance the blood clotting time at a HCP surface is an order of magnitude higher than that at the surface of the initial non-heparinized polymer. 

Fig. 15 SEM images of platelets adhered onto functionalised PE film surface a PE-AA, b PE-PTMG, c PE-POH, d PE-PCe...

During thrombosis platelets adhere to blood vessel walls and aggregate to form a blood clot or thrombus. Platelet aggregation is dependent on the intraplatelet Ca2 + concentration. Nitric oxide is able to inhibit thrombosis by indirectly decreasing... 

See color plate.) The primar/ hemostatic response. Following loss of vascular integrity platelets adhere to subendothelial wall matrix, which triggers their activation. Abbreviations HT, hydroxy tryptamine TFPI, tissue factor pathway inhibitor. 

Schematic view of the role of coagulation factor Xa in arterial thrombosis. After endothelial injury, platelets adhere to the subendothelial matrix. The procoagulant activity of the arterial clot can be attributed to the formation of the prothrombinase complex on the platelet surface which cleaves prothrombin and produces thrombin. Thrombin subsequently acts as a strong agonist of further platelet aggregation.

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