[Correction of the disturbed coagulation circadian rhythm in patients with type 1 diabetes mellitus treated by aspirin chronotherapy].

Circadian rhythms of hemostasis were studied in 20 healthy subjects and 30 patients with type 1 diabetes mellitus before and after conventional therapy (CT) with aspirin (125 mg thrice daily) and chronotherapy (ChN) with aspirin taken once daily at 22.00 (i.e., two hours before the acrophase of the blood coagulation activity revealed during a chronobiological study of hemostasis pripor to the initiation of the treatment). The parameters measured in the study included results of the auticoagulation test, hemolysate of the aggregation test, thrombin time, fibrinogen level, fibrinolytic activity, fibrinolygase activity, and antithrombin III level at 07 h 00 min, 11 hr 00 min, 15 hr 00 min, 19 hr 00 min, 23 hr 00 min, and 03 hr 00 min in 20 healthy subjects and 30 patients with type 1 diabetes mellitus. The data obtained were treated by cosinor analysis as described by F. Halberg. The results suggest internal and external synchronization of circadian rhythms and hemostatic parameters in healthy subjects. Coagulation activity, platelet aggregation in daytime, and blood anticoagulative potential at night increased. In diabetic patients, circadian patterns of hemostasis were disturbed by a combination of enhanced coagulation activity and platelet aggregation with a decrease of anticoagulative potential throughout 24 hours. The maximum disturbance (acrophase) occurred at night. Combined CT with aspirin and insulin therapy caused mean daily levels of plasma and platelet hemostasis to decrease in the absence of normalization of their circadian rhythms. CT not only decreased these parameters and increased anticoagulation activity but also tended to improve chronobiological structure of hemostasis. This effect was reached using thrice lower doses of aspirin.