Coagulation disorders induced by L-asparaginase: Correction with and without fresh-frozen plasma

Objective: L-asparaginase is a potent inhibitor of protein synthesis that may cause deficiencies In several haemostatic proteins: including fibrinogen and antithrombin III, with consequent haemorrhagic or thrombo-embolic complications. Fresh-frozen plasma has been used to prevent these complications Its administration has, however, several disadvantages including hypervolaemia and risk of viral transmission. The aim of the present study was to evaluate the efficacy and the expense of a more specific substitution therapy using heat-inactivated concentrates of fibrinogen and antithrombin III and low-dose heparin as compared to therapy with fresh-frozen plasma. Design: Observational study. Setting: Leukaemia unit of a university hospital. Patients: Thirteen patients with de novo acute lymphoblastic leukaemia received 5,000 U/m(2) L-asparaginase for 14 days. Interventions: Eight patients were substituted with fibrinogen and antithrombin III (group A) and 5 patients with fresh-frozen plasma and antithrombin III (group B). Results: In all 13 patients median plasma levels of fibrinogen and antithrombin III decreased within 7 days after initiation of L-asparaginase treatment to 0.087 g/l (range 0.055-0.303 g/l) and 62% (43-69%), respectively Appropriate substitution by both regimens prevented a further decrease of fibrinogen and antithrombin III. Group A received a median total of 13,350 U antithrombin III (5,000-23,800 U) and 4,000 mg of fibrinogen (2,500-15,000 mg), group B 3,420 mi (1,140-6,270 mi) of fresh-frozen plasma and 8,500 U (2,500-15,000 U) antithrombin III (p=0.107 for the administration of antithrombin III). Drug costs did not differ significantly between group A: 5,083 DM (3,060-10,472 DM) and group B: 4,668 DM (2,184-7,035 DM) (p=0.380). Conclusion: The use of fibrinogen and antithrombin III can replace fresh-frozen plasma during L-asparaginase therapy without increasing the cost of treatment.