COAGULATION DISORDERS INDUCED BY L-ASPARAGINASE - CORRECTION WITH ANDWITHOUT FRESH-FROZEN PLASMA

Objective: L-asparaginase is a potent inhibitor of protein synthesis t hat may cause deficiencies In several haemostatic proteins: including fibrinogen and antithrombin III, with consequent haemorrhagic or throm bo-embolic complications. Fresh-frozen plasma has been used to prevent these complications Its administration has, however, several disadvan tages 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 concentrate s of fibrinogen and antithrombin III and low-dose heparin as compared to therapy with fresh-frozen plasma. Design: Observational study. Sett ing: Leukaemia unit of a university hospital. Patients: Thirteen patie nts with de novo acute lymphoblastic leukaemia received 5,000 U/m(2) L -asparaginase for 14 days. Interventions: Eight patients were substitu ted with fibrinogen and antithrombin III (group A) and 5 patients with fresh-frozen plasma and antithrombin III (group B). Results: In all 1 3 patients median plasma levels of fibrinogen and antithrombin III dec reased 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 Approp riate substitution by both regimens prevented a further decrease of fi brinogen and antithrombin III. Group A received a median total of 13,3 50 U antithrombin III (5,000-23,800 U) and 4,000 mg of fibrinogen (2,5 00-15,000 mg), group B 3,420 mi (1,140-6,270 mi) of fresh-frozen plasm a and 8,500 U (2,500-15,000 U) antithrombin III (p=0.107 for the admin istration of antithrombin III). Drug costs did not differ significantl y 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 antith rombin III can replace fresh-frozen plasma during L-asparaginase thera py without increasing the cost of treatment.