Hypercoagulability during l‐asparaginase treatment: the effect of antithrombin III supplementation in vivo

Abstract

To evaluate the occurrence of hypercoagulability during treatment with l‐asparaginase (l‐ase), thrombin‐antithrombin complex (TAT) and d‐dimer levels in plasma were serially measured in 15 consecutive adult patients with acute lymphoblastic leukaemia or lymphoblastic lymphoma who had recently completed a chemotherapy cycle with cytosine arabinoside and methotrexate. The first eight patients (group A) received i.v. l‐ase alone (20000 U/m² on alternate days over 10 d); the last seven patients (group B) received, in addition to l‐ase, bolus injection of antithrombin concentrate (2000 U) on alternate days for a total of six administrations, beginning with the second l‐ase infusion. Increased levels of TAT (PPP<0·05) and persistence of increased d‐dimer were observed, associated with marked reduction of the anticoagulant activities of protein C, protein S and antithrombin III. At variance, in patients receiving antithrombin III supplementation there was no increase of TAT and a normalization of d‐dimer levels occurred during l‐ase treatment. In these patients, mean plasma antithrombin III activity was maintained at levels higher than 70% of normal throughout the treatment. The rate of decline of fibrinogen, factor IX, protein C and protein S was unaffected by antithrombin III supplementation, indicating that hypercoagulability has little if any relevance for the reduction of coagulation factors and inhibitors induced by l‐ase treatment. The usefulness of antithrombin III concentrates in preventing thromboembolic complications in patients submitted to l‐ase treatment remains to be determined.