Adriamycin (A) Induces a Delayed Hypercoagulable and Prothrombotic State in Rats

F. Delaini, A. Popgi, T. Colombo, L. Komblihtt, I. Reyers, L. Mussoni, M.B. Donati
1979 VIIth International Congress on Thrombosis and Haemostasis   unpublished
The effects of anticancer agents. on the host's haemostatic mechanism have been given limited attention so far. We have studied the early and long-term changes in haemostatic parameters of normal rats given A. Single doses of A (5-10 mg/kg b.w.), at levels active as an anticancer agent in this animal species, did not induce any acute changes in platelets, fibrinogen or fibrinolytic activity, as long as plasma drug levels were measurable. Two weeks later, however, a hypercoagulable stat
more » ... lable stat developed, characterized by increased fibrinogen and F.VIII:C activity, short APTT, low total antithrombin and heparin cofactor levels and markedly depressed fibrinolytic activity (measured by euglobulin and dilute whole blood clot lysis times, plasminogen and antiplasmin amidolytic activity). These changes were dose-related and lasted at least five weeks after treatment. When the plasma antithrombin level was low, this inhibitor could be measured in the urine. A significant reduction in the occlusion time of an aortic loop was observed in A-treated rats. The occurrence of ascites, proteinuria and reduced plasma protein levels in the same animals suggests that A-induced nephrotoxicity (nephrotic syndrome?) could be involved in the pathogenesis of the hypercoagulable and prothrombotic state observed.Supported by Contract NIH-NCI-C-72-3242, NIH (USA) and Italian CNR Project "Control of Tumoral Growth".
doi:10.1055/s-0039-1687538 fatcat:ffnswa7svzfnlln6iyziufja2e