cangrelor and Diabetes-Mellitus--Type-2

Type 2 diabetes (T2D) is associated with several abnormalities in haemostasis predisposing to thrombosis. Moreover, T2D was recently connected with a failure in antiplatelet response to clopidogrel, the most commonly used ADP receptor blocker in clinical practice. Clopidogrel high on-treatment platelet reactivity (HTPR) was repeatedly associated with the risk of ischemic adverse events. Patients with T2D show significantly higher residual platelet reactivity on ADP receptor blocker therapy and are more frequently represented in the group of patients with HTPR. This paper reviews the current knowledge about possible interactions between T2D and ADP receptor blocker therapy.

Topics: Adenosine; Adenosine Monophosphate; Blood Platelets; Cardiovascular Diseases; Clopidogrel; Diabetes Mellitus, Type 2; Drug Resistance; Humans; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Risk Factors; Ticagrelor; Ticlopidine; Treatment Outcome

Platelets from patients with diabetes mellitus are hyperactive. Hyperactivated platelets may contribute to cardiovascular complications and inadequate responses to antiplatelet agents in the setting of diabetes mellitus. However, the underlying mechanism of hyperactivated platelets is not completely understood.. We measured P2Y. Platelet P2Y

Topics: Adenosine Monophosphate; Animals; Blood Platelets; Cell Adhesion Molecules; Cell Line; Chlorides; Cyclic AMP; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Disease Models, Animal; Drug Inverse Agonism; Ferric Compounds; Fibrinolytic Agents; Humans; Male; Microfilament Proteins; NF-kappa B; Phosphoproteins; Platelet Aggregation; Platelet Aggregation Inhibitors; Rats; Rats, Wistar; Reactive Oxygen Species; Receptors, Purinergic P2Y12; Thrombosis

Ninety-eight diabetic patients (type 2) were studied together with 24 healthy normotensive controls. Microaggregates (particle scale, <25 microm) of platelets were detected by a laser scattering system. Microaggregates in the control group showed a time-dependent reversible change; however, they existed continuously in 82 of 98 diabetic patients. When platelets of diabetics were stimulated by a shear stress alone without ADP, 74 also showed spontaneous and irreversible microaggregates even though they were not observed in all control subjects. In control subjects, microaggregates were inhibited by MRS2279 (a P2Y1 antagonist), but not AR-C69931MX (a P2Y12 antagonist). However, AR-C69931MX prevented irreversible microaggregates in diabetic patients. When either aspirin or ticlopidine was administered to diabetic patients with irreversible microaggregates, both drugs significantly decreased microaggregates induced by a low dose of ADP. Ticlopidine additionally reduced the microaggregates induced by shear stress alone. In conclusion, microaggregates of platelets via P2Y12 receptors could play a key role in the hypersensitivity of platelets in diabetic patients, and the measurement of microaggregation could be a useful marker to estimate of thrombogenesis. These findings present a possible new means for patients with diabetes to prevent ischemic events.

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Aged; Diabetes Mellitus, Type 2; Female; Humans; Male; Membrane Proteins; Middle Aged; Piperazines; Piperidines; Platelet Aggregation; Purinergic P2 Receptor Antagonists; Receptors, Purinergic P2; Receptors, Purinergic P2Y12; Reference Values