Fibrinopeptide A changes during remission induction treatment with L-asparaginase in acute lymphoblastic leukemia: evidence for activation of blood coagulation.

L-Asparaginase, a widely used antileukemic agent, inhibits liver protein synthesis leading to hypofibrinogenemia and hypoprothrombinemia together with a severe reduction of antithrombin III and protein C. An increased risk of thrombosis has been reported in leukemic patients treated with this agent. We measured fibrinopeptide A (FPA) changes in 14 patients with acute lymphoblastic leukemia during induction remission treatment with a protocol including L-Asparaginase (10,000 U/m2/daily intravenous for 14 days). At diagnosis, 9/14 patients had FPA level above upper limit of normal range (mean = 4.1 ng/ml). After two days of therapy, FPA rose to 5.2 ng/ml and thereafter showed a slight increase throughout. Antithrombin III, protein C and fibrinogen dropped to its nadir on day 6 and 9. However, the ratio FPA/fibrinogen on a molar basis showed a three-fold increase during this days, demonstrating that the thrombin-dependent consumption of fibrinogen was also increased. In conclusion, our data show that activation of blood coagulation occurs in concomitance with the hemostatic derangement caused by L-Asparaginase. Replacement therapy with the recently available antithrombin III concentrates may be worthy of a clinical trial to test its effectiveness in preventing the thrombotic phenomena reported in these patients.