Abstract
L-asparaginase, a unique anti-tumor agent that depletes L-asparagine, has been used as one of the effective drugs for human leukemias, especially for ALL.
However, this agent has been shown to exhibit various side effects which may cause serious problems clinically.
Although coagulation disturbance due to hypofibrinogenemia, among many side effects by the agent, has been well known, the mechanism involved has not been clearly defined.
In this study, we investigated the mechanism which may induce hypofibrinogenemia by administrating this agent to 10 cases of leukemias (7 cases of ALL, 1 case of AML, 1 case of AUL and 1 case of CML-BC).
1) In 9 out of 10 cases, hypofibrinogenemia (fibrinogen value is below to 200mg/dl) was observed but it did not have any significant correlation to doseor time-dependency.
2) PT and APTT in these cases were prolongedin parallel with the decrease in the fibrinogen value. FDP values were less than 20μg/ml.
3) The activities of other coagulation factores did not necessarily correspond to the decrease in the fibrinogen value.
4) The decrease in fibrinogen was followed by a decrease in serum albumin level.
5) In some cases, dysfunction of fibrinogen was observed at the stage of hypofibrinogenemia.
6) It was speculated that the mechanisms of hypofibrinogenemia after administration of L-asparaginase were due not only to inteference with protein synthesis but also to specific inhibiton of synthesis of fibrinogen and disturbance of its function.
