Journal of Invasive Cardiology

Diabetes and platelet function. At the site of spontaneous or mechanical vessel injury, platelet deposition and thrombosis take place. Disruption of atherosclerotic plaque activates the coagulation cascade, leading to thrombin generation and exposure of deeper components of the plaque, which are powerful platelet activators.^11,12 Since platelets play a major role in acute vascular thrombosis, the increased risk of cardiovascular events among diabetic patients may be, in part, due to altered platelet function.
There is ample evidence that platelets of diabetic patients (“diabetic platelets”) are larger and hyperreactive, showing increased adhesion and aggregation, and increased platelet-dependent thrombin generation.¹³ Patients with diabetes mellitus have increased platelet-surface expression of glycoprotein Ib (GP Ib), which mediates binding to von Willebrand factor, and GP IIb/IIIa, which mediates platelet-fibrin interaction and represents the final common pathway of platelet activation, leading to platelet aggregation.¹ In diabetic patients with stable angina, blood glucose is an independent predictor of platelet-dependent thrombosis, with higher blood glucose levels causing more severe thrombosis.¹³ Moreover, in patients with type 2 diabetes, there is an association between glycemic control and blood thrombogenicity. Osende et al., using the Badimon ex vivo perfusion chamber, showed that improved glycemic control, as indicated by >= 0.5% reduction in HbA1c, resulted in a significant decrease in blood thrombogenicity.¹⁴ In a study of diabetic patients by Davi and colleagues, there was an enhanced biosynthesis of thromboxane A-2, which causes platelet aggregation. Interestingly, tight metabolic control resulted in a significant reduction in thromboxane A-2 biosynthesis.¹⁵ Furthermore, available data indicate that calcium hemostasis is abnormal in platelets of diabetic patients.¹⁶ Since intraplatelet calcium regulates platelet shape change, thromboxane A-2 formation and platelet aggregation, disordered calcium regulation may contribute significantly to abnormal platelet activity in diabetic patients.
Another hallmark of altered vascular hemostasis in diabetic patients is endothelial dysfunction, with hyperglycemia being the primary mediator of the injury. Since glucose entry into platelets does not depend on insulin, intraplatelet glucose concentration mirrors the extracellular concentration. In platelets as well as endothelial cells, elevated glucose levels leads to activation of protein kinase C, decreased production of nitric oxide and increased production of oxygen-free radicals. This ultimately results in impaired platelet-mediated, endothelium-dependent vasodilation.¹ Thus, diabetes as a “prothrombotic” state is characterized by the constellation of endothelial dysfunction, increased platelet adhesiveness and exaggerated platelet aggregation, ultimately resulting in intraluminal thrombus formation (Table 1).¹⁷ In this milieu of “diabetic heightened platelet activity”, therapy with antiplatelet agents is, therefore, expected to confer significant beneficial effects in reducing cardiovascular events.