Elsevier

Thrombosis Research

Volume 104, Issue 2, 15 October 2001, Pages 77-83
Thrombosis Research

REGULAR ARTICLE
Enhanced Platelet Sensitivity to Prostacyclin in Patients in an Active Stage of Takayasu Arteritis

https://doi.org/10.1016/S0049-3848(01)00349-8Get rights and content

Abstract

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 (EC50) 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 EC50 (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 EC50 to collagen and increased plasma thromboxane B2 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-PGF1α 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.

Section snippets

Patient Selection

Twenty-two Japanese patients with TA and 12 gender- and age-matched control subjects entered this study after informed consent. All 22 patients were female, and met the diagnostic criteria for TA based on the report by the American College of Rheumatology [11]. Subject clinical characteristics are summarized in Table 1. Of the 22 patients, 12 were diagnosed as having active disease at the time of the study and the remaining 10 as having inactive disease. Active disease was defined primarily

Platelet Aggregation and Plasma Prostanoids

Fig. 1 shows collagen-induced platelet aggregation in patients with TA and the controls as demonstrated by EC50 values. Although EC50 values in patients with inactive disease were similar to those of the controls, those in patients with active disease were significantly lower, suggesting enhanced platelet aggregation. In accordance with this in vitro finding, plasma TXB2 levels were also found to be increased only in patients with active disease (Fig. 2, top panel). Conversely, in patients with

Discussion

Thrombogenic tendency in TA has been discussed by some reports in regards to coagulation, fibrinolysis and platelet function. Akazawa et al. reported that plasma levels of platelet factor 4, β-thromboglobulin, thrombin-antithrombin III complex and fibrinopeptide A were significantly increased in patients with TA, though they found no differences between active (ESR≥20 mm Hg) and inactive (ESR<20 mm Hg) patients [6]. In the present study, we also confirmed elevation of plasma TXB2, another

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