Supranormal antithrombin III levels induced by concentrate administration are ineffective in quenching thrombin generation in acute promyelocytic leukemia

Coagulation abnormalities occurring in patients with acute promyelocytic leukemia (APL) are partially corrected by heparin administration. This study was undertaken to verify if "supra-normal" levels of antithrombin III (AT-III) are similarly able to quench intravascular thrombin generation triggered by APL cells. Eight patients with APL were randomly assigned to receive either 50 U/kg (Group A) or 100 U/kg (Group B) of an AT-III concentrate, starting on the first day of chemotherapy and continuing for 7 days thereafter. Fibrinopeptide A (FPA), prothrombin fragment F1+2 and thrombin-AT III complexes, measured before and 15 minutes after each AT-III infusion, decreased significantly after each infusion, but the effect was minimal and short-lived, despite the achievement of post-infusion levels of AT-III activity well above 150 % (Group A) or 200 % (Group B). Small amounts of heparin were consistently detected in AT-III concentrates and post-infusion plasma samples. The short-lived quenching of thrombin generation after AT-III concentrate could be partially explained by the infusion of heparin, rather than by supranormal AT-III levels