PLATELET ACTIVATION SUPPORTS THE DEVELOPMENT OF VENOUS THROMBOSIS IN HYPERLIPIDEMIC RATS

This investigation sought to determine how different components of the hemostatic system affect the development of venous thrombosis in rats displaying hyperlipidemia, either on a genetic basis or secondary to metabolic disorders. On employing an experimental model of collagen-tr iggered venous thrombosis, both spontaneously hyperlipidemic (Yoshida strain) and streptozotocin-induced diabetic rats generated about 2.3-f old greater thrombi than normolipidemic controls. This was associated with significant platelet activation, as revealed by increased levels of serum thromboxane B-2 in diabetics (1.5-fold) as well as in Yoshida (8-fold) rats, in comparison with controls. In contrast, ex vivo tota l fibrinolytic activity, as measured by euglobulin lysis time, did not differ between normo-and hyperlipidemic or diabetic animals. Plasmino gen activator inhibitor activity was lower in both Yoshida and diabeti c rats than in controls. However, tissue-type plasminogen activator ac tivity was differently affected by the genetic or the diabetes-related hyperlipidemia, showing significantly lower values in Yoshida (-26%), but significantly higher values in diabetic rats (+29%) than in normo lipidemic controls. We conclude that platelet activation, rather than consistent modifications of the fibrinolytic system, is likely to infl uence the enhanced thrombus development associated with primary or sec ondary forms of hyperlipidemia. (C) 1998 Rapid Science Ltd.