Platelet coronary artery thrombosis

The ACCP Conference on Antithrombotic Therapy recommended against the use of aspirin as the primary method of VTE prophylaxis.2 Antiplatelet drugs clearly reduce the risk of coronary artery and cerebrovascular events in patients with arterial disease, but aspirin produces a very modest reduction in VTE following orthopedic surgeries of the lower extremities. The relative contribution of venous stasis in the pathogenesis of venous thrombosis compared with that of platelets in arterial thrombosis likely explains the reason for this difference. 

About 1.5 million individuals in the USA will have an acute myocardial infarction per year 50% will be fetal and 50 will be a premature event. Thus, there are about 750,000 deaths from coronary artery thrombosis per year. Of these coronary fiurombotic events, 67% of patients harbor a coagulation blood protein or platelet defect leading to thrombosis. Fifty percent of these coagulation protein or platelet defects will be hereditary, thus Figure... 

To maintain hemostasis, blood must be retained in the vasculature as fluid. At the same time, blood components must be able to respond rapidly with a clot when a vascular injury occurs. To repair a vascular injury, platelets in blood first adhere as aggregates to the endothelial cells at the affected site and form an initial blood clot. Platelets then stimulate and activate coagulation factors found in plasma to form a more stable fibrin clot. As the injury is resolved and healed, the clot is degraded. Thrombosis is a pathological event wherein a blood clot occludes a blood vessel, resulting in ischemic necrosis of the tissue fed by the blood vessel. Ischemic necrosis involves local anemia and oxygen deprivation. Thrombosis of a coronary artery may lead to myocardial infarction or unstable angina [20]. 

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. 

Thrombus Formation. The thromboxanes, especially TXA2, cause platelet aggregations that result in blood clot formation.73 It is unclear whether excessive thrombus formation (as in deep vein thrombosis or coronary artery occlusion) is initiated by abnormal thromboxane production. Certainly, inhibition of thromboxane synthesis will help prevent platelet-induced thrombus formation in individuals who are prone to specific types of excessive blood clotting.84... 

Finally, aspirin has also been used to prevent thrombus formation in peripheral veins (deep vein thrombosis [DVT]), and aspirin is sometimes used as an adjunct or alternative to anticoagulants (heparin, warfarin) that are routinely used to treat DVTs.8 Aspirin can likewise be administered to prevent thromboembolism following surgical procedures such as coronary artery bypass, arterial grafts, endarterectomy, and valve replacement 45,78 By preventing platelet-induced thrombogenesis, aspirin helps maintain patency and prevent reocclusion of vessels following these procedures. 

Thrombosis in stenosed human coronary arteries is one of the most common thrombotic diseases leading to unstable angina, acute myocardial infarction or sudden death. Treatment with angioplasty, thrombolysis, or bypass grafts can expose new thrombogenic surfaces and re-thrombosis may occur. The mechanisms responsible for this process include interactions of platelets with the damaged arterial wall and platelet aggregation. 

In order to study new drugs for their antithrombotic potential in coronary arteries, Folts and Rowe (1974) developed the model of periodic acute platelet thrombosis and cyclic flow reductions (CFRs) in stenosed... 

Benedict CR, Mathew B, Rex KA et at. (1986) Correlation of plasma serotonin changes with platelet aggregation in an in vivo dog model of spontaneous occlusive coronary thrombus formation. Circ Res 58 58-67 Guarini S (1996) A highly reproducible model of arterial thrombosis in rats. J Pharmacol Toxicol Meth 35 101-105 Hladovec J (1973) Experimental arterial thrombosis in rats with continuous registration. Thromb Diath Haemorrh 29 407 110... 

Shebuski RJ, Storer BL, Fujita T (1988) Effect of thromboxane synthetase inhibition on the thrombolytic action of tissue-type plasminogen activator in a rabbit model of peripheral arterial thrombosis. Thromb Res 52 381-392 Yasuda T, Gold HK, Fallon JT et al. (1988) Monoclonal antibody against the platelet glycoprotein (GP) Ilb/IIIa receptor prevents coronary artery reocclusion after reperfusion with recombinant tissue type plasminogen activator. J Clin Invest 81 1284-1291... 

Several cases of intravenous immunoglobulin-related thrombosis have been reported (78,79). It can be either venous or arterial (80). It has been suggested that thrombosis can be caused by platelet activation and increased plasma viscosity (79). In patients with vascular risk factors, such as old age, hypertension, and a history of stroke or coronary artery disease, complications, such as myocardial infarction, pulmonary embolism, stroke, and acute spinal cord events, have been described (80). Intravenous immunoglobulin enhances platelet aggregation and the release of adenosine triphosphate in human platelets in vitro. In addition, there is a dose-related increase in plasma viscosity with increasing plasma immunoglobulin concentration (79,80). 

Electrically induced thrombosis [41], [42], [43] electrode placed directly into a coronary artery causing endothelial disruption Platelet rich, but significant fibrin/ red cell content Coronary artery blood flow (e.g. electromagnetic flow probe) Efficacy of antithrombotic agents adjunctive agents in thrombolysis... 

Thrombin induced thrombosis [48] stenosis, endothelial damage (by arterial clamping) and thrombin/blood injection Fibrin and red cell rich initial thrombus platelet rich reocclusion Coronary artery blood flow Adjunctive agents in thrombolysis (but not for effects on lysis of platelet rich thrombus)... 

In the Folts model, tirofiban (0.3mg/kg i.v.) gave 85% inhibition of ADP or collagen induced platelet aggregation, and abolished cyclic flow variations in the canine left circumflex coronary artery, with a short duration of action (18min). In the electrically induced thrombosis model, an infusion of tirofiban (10 g/kg/min), which produced 90% inhibition of platelet aggregation ex vivo, delayed or fully prevented occlusive thrombosis in the canine left circumflex coronary artery [145],... 

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