Circadian variations of plasma levels of blood coagulation/fibrinolysis molecular markers in progressive systemic sclerosis (PSS)

Abstract

We measured plasma levels of the blood coagulation/fibrinolysis molecular markers, thrombin-antithrombin III complex (TAT), fibrinopeptide A (FPA), α 2-plasmin inhibitor plasmin complex (PIC), β-thromboglobulin (β-TG), platelet factor 4 (PF4), at 6:00, 12:00, 18:00 and 24:00 in 10 female patients with progressive systemic sclerosis (PSS) (severe and mild sclerosis groups, each n = 5), 3 cases of dermatomyositis (DM) (M:F = 2:1) and 5 female healthy controls (HC). Corticosteroid (predonisolon; 20–25 mg/day) was administered orally in six patients with PSS and dermatomyositis longer than one month. Plasma levels of TAT increased more than 3 ng/ml in 8 out of 10 cases (80%) of PSS, while the levels increased in only 2 of 8 cases (25%) of the non-PSS groups (DM and HC). The severe sclerosis group of PSS showed a peak at 6:00 in the circadian variations of plasma levels of TAT and FPA, while the mild sclerosis group of PSS showed a peak at 12:00 or 24:00, and both DM and HC at 24:00. However, there was no significant peak in circadian variations of the plasma levels of PIC in the severe sclerosis group of PSS, although there was a peak at 24:00 in other diseases. The synchonized peaks of TAT and PIC were seen in 4 of 8 cases (50%) of the non-PSS group. On the other hand, this synchronization was only detected in 1 of 10 cases (10%) of PSS. The plasma levels of β-TG and PF4 increased in 8 of 10 cases (80%) of PSS, but these levels did not increase in 8 non-PSS cases. Circadian variation of plasma levels of β-TG showed a peak at 6:00 in the severe sclerosis group of PSS, while the mild sclerosis group of PSS, DM and HC revealed peaks at different times of 18:00, 24:00 and 12:00, respectively. Additionally, the plasma levels of β-TG increased more than those of PF4 in the treated group with corticosteroid, although both β-TG and PF4 revealed a statistically significant correlation in the non-treated group. These results may suggest abnormalities of not only platelet activity, but also of blood coagulation/fibrinolysis system in both severe and mild sclerosis groups of PSS.