Acquired alpha-2-antiplasmin deficiency in acute promyelocytic leukaemia.

We report a prospective study in nine consecutive adult patients with acute promyelocytic leukaemia (APL). The study objective was to assess the prevalence of activation of blood coagulation and/or activation of fibrinolysis in APL. Coagulation and fibrinolytic parameters relevant to the objective included antithrombin III, plasminogen, fibrin/fibrinogen degradation products and alpha-2 antiplasmin activity and antigen levels. The results of this study revealed consistently normal antithrombin III levels, both before and in the course of antileukaemic treatment. Plasminogen levels were slightly decreased or normal. However, a distinct alpha-2 antiplasmin activity deficiency in all patients was observed with levels even reaching zero in three patients, during chemotherapy. Alpha-2 antiplasmin activity levels were consistently lower than the alpha-2 antiplasmin antigen levels. The in vitro binding of alpha-2 antiplasmin activity to fibrin clots was severely reduced which appeared to be due to the reduced alpha-2 antiplasmin plasma levels. Upon crossed-immunoelectrophoresis against alpha-2 antiplasmin antiserum two alpha-2 antiplasmin antigen peaks were observed in the plasma of all nine patients. All abnormalities were reversible 4 d after completion of chemotherapy. In a second series of 12 consecutive APL patients we confirmed the consistency of the alpha-2 antiplasmin activity deficiency and normal antithrombin III plasma levels. In addition Protein C activity and antigen levels were normal or near normal in 10 and reduced in two patients. Thrombin-antithrombin III complexes were increased in 10 and normal in two patients. We conclude that some activation of blood coagulation is present in APL (increased thrombin-antithrombin III complex levels) but its contribution to the coagulopathy seems to be minor (normal antithrombin III and only slightly reduced protein C levels). The observed reduced alpha-2 antiplasmin content of the fibrin clot in vitro may result in vivo in a fibrin clot that is highly susceptible to fibrin degradation, thus aggravating the coagulopathy in APL.