Platelet activity and

Fibrinolytic agents have prothrombotic properties as well. The plasmin generated by thrombolysis leads to the production of thrombin, which is a potent platelet activator and converts fibrinogen to fibrin. Indeed, studies have shown early reocclusion in as many as 17% of the patients treated with lAT and 34% of the patients treated with IV rt-PA. Therefore, a strong rationale exists for the adjuvant use of antithrombotic agents. 

Administration of clopidogrel is recommended for all patients with STE ACS (Table 5—2).3 Clopidogrel blocks adenosine diphosphate receptors on platelets, preventing the expression of glycoprotein Ilb/IIIa receptors and thus platelet activation and aggregation. 

Schafer A, Schulz C, Eigenthaler M, et al. Novel role of the membrane-bound chemokine fractalkine in platelet activation and adhesion. Blood 2004 103(2) 407—412. 

Human platelets Platelet activation and aggregation by inducing Ca2+ influx [112]... 

Fig. 9.1. A dysfunctional or injured endothelium is at the basis for initiation of and progression to atherosclerosis. Several mechanisms, such as adhesion molecules or liberation of von Willebrand factor (vWf, upper panel), determine a series of phenomena, including platelet activation and aggregation. This participation of platelets involves the implication of molecules like glycoprotein Ilb/IIIa, fibrinogen, and von Willebrand factor. The endothelium also acts as a source of signals that regulate local functions, including VSMCs (lower panel). A list of the most relevant messengers produced by a functional and a dysfunctonal endothelium is presented in the lower panel...

Detwiler and co-workers were the first to demonstrate a role for csPDI in platelet physiology (Chen et al, 1995 Essex et al, 1995). Essex and co-workers (1999, 2001) and Hogg and co-workers (Burgess et al., 2000) showed that the inactivation of csPDI with anti-PDI antibodies and thiol alkylating agents inhibited platelet activation and aggregation. Recent studies have identified two distinct activities for csPDI. 

The pathogenesis of TTP is complex, and possibly involves a variety of mechanisms associated with endothelial cell and platelet activation and injury. Recently, however, the deficiency of vWF cleaving prolease aclivily has been idenlified as a hallmark of TTP (67, 68). In normal individuals, vWF is secreted from platelets and endothelial cells as variously sized multimers, resulting from the crosslinking of vWF monomers by disulfide bonds into multimers containing a minimum of 2 to a maximum of 50-100 monomer subunits. 

Kieffer, N., Guichard, J., and Breton-Gorius, J., Dynamic redistribution of major platelet surface receptors after contact-induced platelet activation and spreading. Am. J. Pathol. 140, 57-73... 

The drug has a short half-life with clearance that is 20% renal and the remainder metabolic. Bivalirudin also inhibits platelet activation and has been FDA-approved for use in percutaneous coronary angioplasty. 

In four patients with von Willebrand disease, desmopressin caused a significant but transient reduction in platelet count without an increase in plasma glycocalicin concentrations nor enhanced expression of P selectin, suggesting that acute thrombocytopenia after the administration of desmopressin in type 2B von Willebrand disease is not related to platelet activation and consumption (68). 

Demrow HS, Slane PR, Folts JD. 1995. Administration of wine and grape juice inhibits in-vivo platelet activity and thrombosis in stenosed canine coronary arteries. Circulation 91 1182-1188. 

Rein D, Paglieroni TG, Wun T, Pearson DA, Schmitz FIFI, Gosselin R, Keen CL. 2000. Cocoa inhibits platelet activation and function. Am J Clin Nutr 72 30-35. 

The chemotaxis of mononuclear leukocytes and the migration, growth, and activation of the multiple cell types within atherosclerotic lesions are critical for the chronic inflammatory and fibroproliferative response in atherosclerosis (Ml). Chemokine-mediated attraction of leukocytes to tissues has been shown in atherosclerotic lesions (G8). Studies using knockout and transgenic murine models indicated that chemokine receptor/ligand interactions are crucial in the development of atherosclerosis (P6). Moreover, chemokines may also interfere with smooth muscle cell migration and growth, and platelet activation and other well-defined features of the atherosclerotic process (A2). 

The above-mentioned agonists are important factors in platelets activation and in the thrombotic process and many of the receptors are targets in the development of drugs for thrombosis prevention (Table I). 

---