Age-related changes in coagulation, fibrinolysis, and platelet aggregationin male WBN/Kob rats

We investigated the age-related changes in blood coagulation, fibrinolysis, and platelet aggregation in male WBN/Kob rats, animals that exhibit sponta neously diabetes mellitus at more than 6 months of age. The rats aged 6 mon ths or more showed significant hyperglycemia, hypoinsulinemia, and hyperlip idemia. As changes in coagulation parameters, the data indicated significan t increases in factors II, V, VII, VIII, IX, X, and XII activities; a signi ficant decrease in antithrombin III activity in rats more than 6 months of age; significant increases in fibrinogen level and factor XI activity; and significant decreases in prothrombin time and activated partial thromboplas tin time in those more than 9 months of age. As changes in fibrinolytic par ameters, the animals showed significant decreases in plasminogen and tissue -type plasminogen activator, and significant increases in alpha(2)-plasmin inhibitor and plasminogen activator inhibitor at more than 6 months of age. In addition, there were significant correlations between the plasma levels of coagulation/fibrinolytic markers and the 4-hour fasting glucose or lipi ds, Furthermore: they displayed significant increases in ADP- or collagen-i nduced platelet aggregation and in cholesterol/phospholipid molar ratio in platelets at more than 9 months of age. The increase in cholesterol/phospho lipid ratio may be responsible for hyperaggregation of platelets in diabeti c animals. These findings suggest that WBN/Kob rats are suitable for resear ch on blood coagulation abnormalities in diabetes. However, further studies are needed to clarify the details of the mechanisms involved. (C) 2000 Els evier Science Ltd. All rights reserved.