thromboxane-b2 and Takayasu-Arteritis

The present study, using patients with Takayasu's disease (pulseless disease), characterized by segmentally affected arterial lesions and stenotic conditions with a nonspecific inflammatory morbid condition, was designed to assess whether or not a low dose of aspirin can practically exert its preventive effect against the aggregation of platelets that have just passed along a rough-surfaced arterial wall. Twenty Japanese women with Takayasu's disease were selected under the following criteria: A unilateral upper extremity was angiographically confirmed to be affected with the disease, while the contralateral limb was almost normal. Systolic blood pressure on the affected side was almost half that on the nonaffected side. The patients showed neither a positive CRP nor an accentuated ESR. In these patients, mean plasma levels of TXB2 and 3 microM ADP-induced platelet aggregation in blood obtained from the affected side were 156.5 +/- 17.7 pg/ml, and 59.5 +/- 6.0%, respectively, which were significantly high as compared with 104.5 +/- 17.6 and 41.7 +/- 8.8%, respectively, in samples from the nonaffected side. Forty and eighty mg of aspirin per day administered to two randomly composed groups, respectively, showed an improvement in platelet aggregability and TXB2 levels on the nonaffected side. In the affected limbs, though 80 mg/day led to significant decreases in TXB2 levels (108.0 +/- 7.8 pg/ml, p less than 0.05) and platelet aggregability (21.3 +/- 7.6%), the 40-mg regimen showed no significant reductions (134.6 +/- 9.4 pg/ml, 35.6 +/- 17.1%). Plasma levels of 6-keto PGF1 alpha revealed no differences between 40- and 80-mg regimens, or between before and after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aortic Arch Syndromes; Arm; Aspirin; Clinical Trials as Topic; Female; Humans; Platelet Aggregation; Random Allocation; Takayasu Arteritis; Thrombosis; Thromboxane B2

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.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Blood Platelets; Case-Control Studies; Collagen; Epoprostenol; Female; Humans; Iloprost; Kinetics; Male; Middle Aged; Platelet Aggregation; Takayasu Arteritis; Thromboxane B2

Plasma thromboxane B2 (TXB2), cyclic AMP and cyclic GMP levels in 31 women with Takayasu disease were measured and findings were compared with data on 34 age-matched healthy Japanese. Platelet aggregation determined by the screen filtration pressure (SEP) method and pulmonary lesions assessed by scintillation were studied in 21 patients. Plasma TXB2 levels in patients with Takayasu disease were 265.8 +/- 20.4 pg/ml, which were statistically higher than the levels of 196.3 +/- 10.7 in healthy controls. On the contrary, cyclic AMP levels in the patients were 9.6 +/- 0.7 pmols/ml, statistically lower levels than 13.5 +/- 1.0 seen in the healthy controls. A positive correlation among cyclic AMP, cyclic GMP and TXB2 levels was confirmed only in the controls. SEP values in the patients with pulmonary lesions were significantly higher than in those without lesions and also in the controls. A positive correlation was obtained between SEP and TXB2 levels in healthy controls, but not in the patients. Thus, thromboxane A2 may play an important role in the pathology of Takayasu disease.

Topics: Adult; Aortic Arch Syndromes; Cyclic AMP; Cyclic GMP; Female; Humans; Platelet Aggregation; Takayasu Arteritis; Thromboxane B2; Thromboxanes

In our ongoing studies of the interrelationship between platelets and the vascular wall we found that an accurate estimate could be made of the clinical condition and more effective therapy prescribed when we monitored alterations in the plasma levels of TXB2. For this purpose we devised a radioimmunoassay with I125-TXB2-Tyramide. Patients with ischemic heart disorders, cerebral apoplexy, diabetes mellitus, Buerger's disease, Takayasu disease etc., all had statistically high levels of TXB2 as compared with healthy controls. In particular, patients with myocardial infarction, cerebral thrombosis and/or hemorrhage all revealed increases in levels of TXB2 and these levels increased in parallel with a worsening of the clinical condition, and there was always a re-increase in TXB2 level before a recurrence of an attack. As plasma TXB2 levels clearly reflect thrombogenic disorders, the assessment of these levels on a routine basis, enables a more accurate diagnosis, an indication of possible recurrences, and more effective chemotherapy and rehabilitation.

Topics: Adolescent; Adult; Arteriosclerosis; Arteriosclerosis Obliterans; Child; Chromatography, Gel; Circadian Rhythm; Coronary Disease; Diabetes Mellitus; Dinoprost; Female; Humans; Intracranial Embolism and Thrombosis; Male; Middle Aged; Prostaglandins F; Takayasu Arteritis; Thromboangiitis Obliterans; Thromboxane B2; Thromboxanes