Effect of Clopidogrel on Platelet CD Markers in Normal Individuals and in Patients with Untreated Type 2 Diabetes Mellitus.

The objective of this study was to evaluate the effect of clopidogrel response in patients with untreated type 2 diabetes mellitus as compared with normal individuals. One hundred and seven subjects i.e. 32 normal and 75 patients with untreated type 2 diabetes mellitus were enrolled in this study. In the first step, normal subjects as well as diabetic patients were selected and tested for various laboratory parameters and platelets flow cytometry. In the second step, an antiplatelet drug (clopidogrel) was administered for 10 days to each individual enrolled in the study. After 10 days blood samples were collected for platelets flow cytometry. CD41 and CD61 did not show any change after the administration of clopidogrel in resting and activated platelets. CD63 and CD62p positivity was increased in normal and in diabetic patients' platelets after activation with ADP before clopidogrel. It was decreased in normal resting and ADP stimulated platelets after clopidogrel treatment. CD63 and CD62p positivity in resting and ADP stimulated patients' platelets was also decreased after clopidogrel treatment. The change was, however, not as marked as in normal subjects.

Functional status of vascular endothelium in diabetes mellitus.

Normal endothelial cells synthesize and release biologically active substances. These substances maintain homeostasis through adequate blood flow, delivery of nutrients, activation and inhibition of coagulation proteins, prevention of thrombosis and diapedesis of leukocyte. Endothelial dysfunction implies failure of vascular endothelium to perform its normal functions of vasodilatation and vasoconstriction. It results from an imbalance between endothelium derived constricting and relaxing factors. Altered endothelial cell activity predisposes to increased production of vasoconstrictors, i.e., prostaglandins, endothelins, glycated proteins, endothelial adhesion molecules and platelet and vascular growth factors. These changes enhance vasomotor tone, vascular permeability, growth and remodeling of the vessels. Diabetes is associated with abnormalities of vascular endothelium. Several regulatory vasodilators and vasoconstrictors are altered in diabetes leading to diabetic vascular complications. Balance between dilating and constricting substances is altered and is shifted towards vasoconstriction in diabetes. Disturbances in the endothelial functions lead to increased platelet adhesion and aggregation in patients with diabetes. Activated platelets interact with endothelial cells and leukocytes in the genesis of atherosclerosis. High level of Von Willebrand factor (vWF) is a consistent finding in diabetes. Increased vWF level is one of the major risk factors for the development of micro vascular complications. High levels of vWF may predict cardiovascular disease progression in diabetes mellitus.

Platelet receptors; an instrumental of platelet physiology.

Platelets play an important role in hemostasis, inflammation, host defense, tumor growth and metastasis. Platelets receptors are instrumental in platelet-platelet aggregation and interaction of platelets with leukocytes, endothelial cells and coagulation factors. These receptors are also the targets for antiplatelet drugs. This review focuses on the role of platelet receptors in human physiology. Data were extracted from peer-reviewed journals using MEDLINE and EMBASE databases, and the following terms (platelets, platelet receptors, CD markers, integrins, tetraspanins, transmembrane receptors, prostaglandin receptors, immunoglobulin superfamily receptors) were used.

New horizons in platelets flow cytometry.

Platelet flow cytometry is an emerging tool in diagnostic and therapeutic hematology. It is eminently suited to study the expression of platelet surface receptors both qualitatively as well as quantitatively. It can serve as a useful marker for the documentation of in vivo platelet activation, and thus, fore-warn the risk of thromboembolism in patients with diabetes mellitus, coronary syndromes, peripheral vascular diseases, and pre-eclampsia. This technique can also be extended to study and compare the effect of various antiplatelet drugs on the level of activation of platelets and to establish any dose-effect relationship of these drugs. Topographical localization of platelet granules and study of platelet-platelet and platelet-leukocyte interaction is also possible by this procedure. All these parameters serve as pointers towards the presence of activated platelets in the circulation with its thromboembolic consequences. This is a simple reliable and cost effective technique which has a wide application in the diagnosis of various inherited and acquired platelet disorders. Study of platelet cluster of differentiation (CD) markers in various inherited disorders i.e. Bernard Soulier's disease, von Willebrand disease, Glanzman's disease, and Grey platelet syndrome may help categories the molecular lesions in these oft under-studied disorders.