Thrombosis, prostaglandins

Ali, M. and Thomson, M. (1995) Consumption of a garlic clove a day could be beneficial in preventing thrombosis. Prostaglandins Leukot. Essent. Fatty Acids. 53 211-212. 

In addition to their effects on coronary thrombosis, prostaglandins may play a role in modulating the degree of tissue injury in acute myocardial infarction. Infusion of prostacyclin in the isolated perfused heart limits hypoxic injury independent of its effects on tissue perfusion or platelet function, suggesting that prostacyclin exerts a direct myoprotective effect . Prostacyclin biosynthesis increases markedly following acute myocardial infarction in... 

NS AIDs Cyclooxygenases (COX-1, COX-2) l Prostaglandins l Thromboxanes l Sensitization of sensory neurons f Inhibition of spinal neurons Nonselective gastrointestinal ulcers, perforation, bleeding, renal impairment COX-2 thrombosis, myocardial infarction, stroke... 

Bourgain RH, Andries R, Braquet P. (1987). Effect of ginkgolide PAF-acether antagonists on arterial thrombosis. Adv Prostaglandin, Thromboxane, Leukotriene Res. 17B 815-17. 

Carbajal, D., M. L. Arruzazabala, R. Mas, V. Molina, and S.Valdes. Effect of policosanol on experimental thrombosis models. Prostaglandins Leukot Es-sent Fatty Acids 1994 50(5) 249-251. 

Abbreviations CEL, cellulose CHC, chlorohydrocarbon GP, glycoprotein GR. gianturco-roubin NA, not available Neo-R, neointima reduction PGI2. prostaglandin I2 PLLA(PLA), poly-L-lactic acid P-S, Palmaz-Schatz PUR. polyurethane Thr-R, thrombosis reduction. PEG. polyethyleneglycol ... 

Tada M, Esumi K, Yamageshi M et al. (1984) Reduction of prostaglandin synthesis as a possible cause of transient flow reduction in a partially constricted canine coronary artery. Mol Cell Biol 16 1137-1149 Uchida Y, Yoshimoto N, Murao S (1975) Cyclic fluctuations in coronary blood pressure and flow induced by coronary artery constriction. Jpn Heart J 16 454—464 Warltier DC, Lamping KA, Pelc LR, Gross GJ (1987) A canine model of thrombin-induced coronary artery thrombosis Effects of intracoronary streptokinase on regional myocardial blood flow, contractile function, and infarct size. J Pharmacol Meth 18 305-318... 

ASPIRIN, PROSTAGLANDINS AND PLATELET FUNCTION PHARMACOLOGY AND THROMBOSIS... 

These differences in the prostaglandins synthesised in endothelium and platelets are important. Intact vascular endothelium does not activate platelets because of the high concentration of prostacyclin in the intima. Subintimal tissues contain little prostacyclin and platelets, under the influence of thromboxane-Aj, immediately adhere and aggregate at any breach in the intima. Atheromatous plaques do not generate prostacyclin—which explains platelet adhesion and thrombosis at these sites. 

A causal relation between celecoxib and these thrombotic events cannot be established with certainty on the basis of the available evidence. However, the temporal relation between the start of treatment and the thrombotic event was impressive, at least in three patients, and the findings were consistent with the hypothesis that thrombosis is an adverse consequence of reduced production of systemic prostaglandin I2 brought about by COX-2 inhibition. Reduced synthesis of prostaglandin I2 may act in concert with other thrombotic risk factors (such as those occurring in this series of patients) to precipitate acute vascular occlusion. 

Omega-3 fatty acids are long-chain polyunsaturated fatty acids. The parent fatty acid of this group is alpha-linolenic acid, an essential fatty acid that the body is unable to synthesize alpha-linolenic acid can be converted in the body to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In animals and man, these acids reduce the production of several compounds that are involved in inflammation and thrombosis, such as eicosanoids (prostaglandins, thromboxanes, prostacyclin, and leukotrienes) and cytokines (interleukin II-l) (1). The extent of the conversion of alpha-linolenic acid to EPA and DHA is unclear. The conversion process appears to be inhibited by a high intake of linoleic acid, another essential fatty acid (2). In addition, alpha-linolenic acid is found in dark green vegetables and the oils of certain nuts and seeds, especially rape seeds and soya beans. 

Summary - Many diverse novel compounds that inhibit different platelet functions show great promise, not only for potential anti-thrombotic agents, but also for more specific effects on prostaglandin and/or thromboxane A2 synthesis, and serotonin or calcium uptake and release. Many active compounds can be used as tools in the search toward a more complete understanding of the physiologic interactions of the hemostatic mechanisms. This better understanding would lead to the development and use of more potent and selective synthetic compounds in the inhibition of platelet aggregation and fibrin formation, and in the enhancement of fibrinolysis for the control of both arterial and venous thrombosis. It is hoped that some of these new compounds will be evaluated clinically in the near fu ture. 

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