Enhanced platelet sensitivity to prostacyclin in patients in an active stage of Takayasu arteritis.
Patients in an active stage of Takayasu arteritis are often complicated with thrombosis in the affected vessels. We investigated whether alteration of platelet sensitivity to prostacyclin is involved in platelet function in these patients. Twelve female patients in an active stage (48.3+/-11.8 years, mean+/-S.D.), diagnosed clinically by a persistently elevated erythrocyte sedimentation rate (>40 mm/h) with typical symptoms, along with 10 gender- and age-matched patients in an inactive stage and 12 control subjects were enrolled. Half-maximal concentration (EC(50)) for platelet aggregation to collagen was determined in the presence and absence of 1 nM iloprost, a stable prostacyclin analog. Sensitivity of platelets to prostacyclin was quantified by the ratio of EC(50) (R) in the presence of iloprost to that in its absence. Patients in an active stage exhibited enhanced platelet aggregation, as demonstrated by significantly lower EC(50) to collagen and increased plasma thromboxane B(2) concentration. However, R values in these patients were significantly higher (4.00+/-1.05; P<.001) than those in the inactive patients or controls (2.58+/-0.62 and 2.43+/-0.68, respectively), suggesting enhanced sensitivity to prostacyclin in patients with active disease. Plasma 6-keto-PGF1 alpha levels were lower in the active patients than those in other groups of subjects. We conclude that platelets in an active stage of TA may be sensitive not only to collagen but also to prostacyclin. The increase in sensitivity of the platelets to prostacyclin could be a compensatory mechanism against a decrease in the prostanoid production, presumably associated with endothelial dysfunction.
Watanabe
T
T
Department of Cardiovascular Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Kishi
Y
Y
Numano
F
F
Isobe
M
M
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000328:Adult; D001792:Blood Platelets / Q000187:drug effects*; D016022:Case-Control Studies; D003094:Collagen / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D016285:Iloprost / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D013625:Takayasu Arteritis / Q000097:blood*; D013929:Thromboxane B2 / Q000097:blood
D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D003094:Collagen; D011464:Epoprostenol; D016285:Iloprost