The Activated Megakaryocyte-Platelet-System Vascular Disease: Focus on Diabetes

Abstract

Vascular diseases and related complications still represent the main cause of death. In diabetes neuropathy, nephropathy, retinopathy and disturbed nutritive tissue perfusion result from reduced capillary microcirculation. These disturbances are diabetes specific, whereas macroangiopathy does not differ structurally from atherosclerotic lesions of non-diabetic subjects, but leads to accelerated cerebral, coronary and peripheral artery disease. Occurrence of life terminating thrombotic events which are superimposed to those vascular lesions is increased. Thus, morbidity and mortality of diabetes depend mainly on vascular complications. Normal blood flow is a prerequisite of adequate organ perfusion and results from vasomotion, plasma components, corpuscular blood elements, vascular architecture and the undisturbed interaction of these components at the endothelial interface. Functional thromboresistance of the endothelial layer is reduced in the diabetic state. Increased intravascular thrombin generation, reduced fibrinolytic potential and hyperactive platelets lead to a prethrombotic state. This thrombotic diathesis raises the permanent danger of acute flow disruption. Activated platelets operate by three mechanisms: 1. microembolization of the capillaries; 2. local progression of preexisting vascular lesions by secretion of constrictive, mitogenic, and oxidative substances; and 3. trigger of the prognosis limiting arterial thrombotic event. We were able to show that the increased functional properties of diabetic platelets result from the primary release of larger platelets with enhanced thromboxane formation capacity and increased numbers of functional glycoprotein receptors GPIB and GPIIB/IIIA which are synthesized in the megakaryocytes. The megakaryocyte-platelet system is turned on in diabetes mellitus. It could be demonstrated with the Duesseldorf III method of flow cytometric activation marker testing (CD62, CD63, thrombospondin) that predominantly large platelets circulate in an activated state in diabetes mellitus. From these considerations antiplatelet therapy may be regarded as a useful adjunct to metabolic therapy.

Key words:

Platelets - megakaryocytes - flow cytometry - diabetes - antiplatelet therapy