Platelet Function and Hyperglycemia in Acute Coronary Syndrome

Abstract

The literature provides strong evidence showing that platelet function is altered in patients with diabetes mellitus (DM) and that the platelet hyperactivation associated with hyperglycemia is produced by a number of thromboxane A2-independent pathways, such as those responsible for the release of adenosine diphosphatase, thrombin, epinephrine, and von Willebrand factor, among others. Being that they are independent of thromboxane A2, none of these platelet activation pathways are affected by the potential beneficial effect of the classical antiplatelet therapy with acetylsalicylic acid (ASA) or more modern compounds like clopidogrel. For this reason, the search for novel therapeutic approaches designed to control platelet reactivity, especially in diabetic individuals and not only in atherosclerosis not associated with DM, has been an object of interest in recent years, particularly if we take into consideration that diabetics have a certain resistance to the antiplatelet effect of ASA. Diabetic thrombocytopathy is due to the activation of multiple pathways that play a role in platelet function, the most relevant of which are the modification of platelet membrane components, the alteration of calcium and magnesium homeostasis (increasing and decreasing mobilization, respectively), increases in arachidonic acid metabolism and in thromboxane A2 synthesis, a decrease in prostacyclin and nitric oxide synthesis, and increased expression of certain adhesion molecules such as glycoprotein IIb/IIIa (GPIIb/IIIa) and P-selectin. The platelets of patients with DM, both type 1 and type 2, exhibit increased reactivity in early stages of the disease, and these phenomena are relevant because they contribute to the excessive rates of cardiovascular morbidity and mortality associated with this disease. Thus, the knowledge of these plateletrelated phenomena from the pathophysiological point of view, and of their eventual normalization, has been of great interest; in fact, the clinical practice guidelines on DM have incorporated, to a greater or lesser extent, recommendations concerning antiplatelet therapy. The platelets of diabetic patients express greater amounts of adhesion molecules such as activated GPIIb/IIIa, lysosomal GP53, thrombospondin, and P-selectin. In addition to supporting greater platelet aggregability, this may play a role in