Pioglitazone inhibits platelet function and potentiates the effects of aspirin: a prospective observation study.
BACKGROUND
Thiazolidinediones (TZDs) are agonists of PPARγ and exert beneficial metabolic effects in patients with diabetes. They may also affect platelet function.


OBJECTIVE
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 30mg of pioglitazone. PRP was prepared and platelet aggregation and release were evaluated using ADP, collagen and arachidonic acid as agonists. Subjects returned at 6-9days later after ingesting a single 81mg dose of aspirin and a third blood sample was obtained. The subjects then again ingested 30mg 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, TXB(2) release was 32,719±3,585pg/ml which was significantly reduced compared to baseline (42,075±4,479, P=0.0004). Pioglitazone also potentiated the inhibition of TXB(2) release by aspirin.


CONCLUSIONS
Pioglitazone inhibits platelet function and potentiates the inhibitory effects of aspirin.
University of Rochester Medical Center, Department of Medicine - Hematology/Oncology, Rochester, NY 14642, USA.
John
J
Mongan
Hanna Z
HZ
Mieszczanska
Brian H
BH
Smith
Susan P
SP
Messing
Richard P
RP
Phipps
Charles W
CW
Francis
D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D016022:Case-Control Studies; D003920:Diabetes Mellitus / Q000097:blood* / Q000188:drug therapy*; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D010974:Platelet Aggregation / Q000187:drug effects; D010979:Platelet Function Tests; D011446:Prospective Studies; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000494:pharmacology*
D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D001241:Aspirin; D000077205:Pioglitazone