ABSTRACT

Endothelial cells are the principal site of production, storage and release of fibrinolytic activators, that is, u-PA and t-PA. Impaired release of plasminogen activators from the endothelium results in a reduction in fibrinolytic activity in vivo and may contribute to the pathogenesis of thrombus formation.42 In addition, endothelial cells may produce PAI-1, the main inhibitor of plasminogen activation, and it has been shown in vitro that activation of endothelial cells results in enhanced production and release of this inhibitor of fibrinolysis. Elevated levels of PAI-1 are associated with the occurrence of thrombotic disease.43 Recent reports indicate that endothelial damage may result in endothelial dysfunction, leading to impaired release of plasminogen activators and increased levels of PAI-1, and thus resulting in an overall antifibrinolytic state. For example, it has been shown that cyclosporin A-induced damage to endothelial cells results in a reduction of fibrinolytic activity caused by these mechanisms.44 In cancer patients with TTP, a similar pattern has been shown regarding the fibrinolytic activation and inhibition: impaired release of plasminogen activators and enhanced levels of PAI-1.45,46 There are only limited data in the literature on endothelial function as related to fibrinolysis after treatment with high-dose chemotherapy;47 however, on the basis of the above-mentioned observations, it may be hypothesized that chemotherapy-induced endothelial injury results in an antifibrinolytic condition that may contribute to the pathogenesis of thrombotic microangiopathy.