Activationof the Kinin-FormingSystem

Venous blood kininogen is significantly decreased during therapy with cyclophosphamide in cases of advanced breast cancer. The maximum decrease in plasma kininogen coincided with onset of maximal leukopenia in the peripheral venous blood. In vitro studies showed that both human whole blood and mononuclear cell suspensions liberate free kinin when incubated with cyclophosphamide, but plateletfree human plasma does not. Evidently, the kininforming system is activated during therapy with cyclophosphamide, and this may account for some of its reported side effects. The in vitro studies suggest that this activation results from damage to peripheral blood leukocytes by the cyclophosphamide, with the release of intracellular proteases.