Pioglitazone inhibits platelet function and potentiates the effects of aspirin: A prospective observation study

• Published in: Thrombosis research 2012-06, Vol.129 (6), p.760-764
• Main Authors: Mongan, John, Mieszczanska, Hanna Z, Smith, Brian H, Messing, Susan P, Phipps, Richard P, Francis, Charles W
• Format: Article
• Language: English
• Subjects: aspirin; Aspirin - administration & dosage; Aspirin - pharmacology; Biological and medical sciences; Blood and lymphatic vessels; Blood Platelets - drug effects; Blood Platelets - physiology; Cardiology. Vascular system; Cardiovascular system; Case-Control Studies; Diabetes Mellitus - blood; Diabetes Mellitus - drug therapy; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Drug Synergism; Female; Hematology, Oncology and Palliative Medicine; Humans; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - pharmacology; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; pioglitazone; Platelet Aggregation - drug effects; platelet function; Platelet Function Tests; platelet release; Prospective Studies; thiazolidinediones; Thiazolidinediones - administration & dosage; Thiazolidinediones - pharmacology; Vasodilator agents. Cerebral vasodilators
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/j.thromres.2011.12.019

Abstract Background Thiazolidinediones (TZDs) are agonists of PPARγ and exert beneficial metabolic effects in patients with diabetes. They may also affect platelet function. Objectives To characterize potential platelet inhibitory effect of pioglitazone alone and in the presence of aspirin. Methods 20 normal and 20 diabetic subjects were enrolled in a prospective study. On day 1, a blood sample was obtained at baseline and a second one after ingestion of 30 mg of pioglitazone. PRP was prepared and platelet aggregation and release were evaluated using ADP, collagen and arachidonic acid as agonists. Subjects returned at 6–9 days later after ingesting a single 81 mg dose of aspirin and a third blood sample was obtained. The subjects then again ingested 30 mg of pioglitazone and a fourth and final blood sample was obtained. Platelet aggregation and release were measured. PRP was incubated with thrombin to activate platelets, and the serum was separated and assayed for thromboxane B2, TGFβ and CD40L Results Pioglitazone alone did not affect aggregation with arachidonic acid. However, following ingestion of both aspirin and pioglitazone aggregation was significantly decreased compared to aspirin alone (P < 0.0001). Pioglitazone also potentiated aspirin-induced inhibition of ATP release using either arachidonic acid or collagen. Following pioglitazone alone, TXB2 release was 32,719 ± 3,585 pg/ml which was significantly reduced compared to baseline (42,075 ± 4,479, P = 0.0004). Pioglitazone also potentiated the inhibition of TXB2 release by aspirin. Conclusion Pioglitazone inhibits platelet function and potentiates the inhibitory effects of aspirin.