L-asparaginase induced antithrombin III deficiency: evidence against the production of a hypercoagulable state

L-asparaginase, a chemotherapeutic agent employed in the treatment of acute lymphocytic leukemia (ALL), is known to depress the synthesis of numerous plasma proteins. The plasma concentration of the major protease inhibitor of the coagulation mechanism, antithrombin III, is substantially decreased in patients receiving this drug. This observation has generated speculation that L-asparaginase may induce a hypercoagulable state in humans. To examine this hypothesis, we studied ten patients with ALL in remission who were being treated with the above chemotherapeutic agent. Our data revealed that infusion of this enzyme leads to a marked decrease in the plasma concentrations of prothrombin as well as antithrombin III. However, we have also observed a constant level of thrombin generation during the same period of time as monitored by plasma levels of prothrombin activation fragment (F1 + 2) and thrombin-antithrombin complex (TAT). Based upon these findings we suggest that administration of L-asparaginase does not usually lead to the induction of a hypercoagulable state.