Evidence of a Hypercoagulable State in Patients with Acute Lymphoblastic Leukemia Treated with Low Dose of E.coli L-Asparaginase: A GIMEMA Study^[*]

Summary

Blood coagulation abnormalities induced by administration of E. coli L-asparaginase were investigated in 25 patients with acute lymphoblastic leukemia treated according to the GIMEMA ALL 0288 trial. Dosage of L-asparaginase was relatively low (6,000 U/m²/day for 7 days total dose 42,000 U/m²) as compared to the conventional dosages (120,000-140,000 U/m² over 10–14 days). A significant decrease in fibronogen, plasminogen, alpha₂-antiplasmin and antithrombin III was observed from day IV of L-asparaginase and it was maximum on day VIII, with return to the baseline levels on day XV. Protein C levels had only a borderline reduction, while no modification of protein S or factor VII was observed. Two of the patients investigated developed thrombosis. The presence of a prothrombotic state induced even by this low dosage of E. coli L-asparaginase was suggested by a significant increase of sensitive markers of hypercoagulability such as fibrinopeptide A, thrombin-antithrombin complexes, and prothrombin fragment F1 + 2.

^*GIMEMA Cooperative Group: F. Mandelli (Chairman); P. Leoni, M. Montillo, 1st. Clinica Medica Clinica di Ematologia, Ancona; E. Volpe, N. Cantore, Servizio di Ematologia, Avellino; S. V. Zagonel, A. Pinto, Centro di Riferimento Oncologico, Aviano (PN); V. Liso, Servizio di Ematlogia, Bari; S. Tura, G. Visani, 1st. Ematologia “Seragnoli”, Bologna; G. Broccia, W. Deplano, Div. Ematologia, Cagliari; E. Cacciola, G. Milone, Cattedra di Ematlogia, Catania; A. Alberti, A. Peta, Div. Ematologia, Catanzaro; E. Bianchini, A. Porcellini, Sez. Ematologia Centro Trapianti di Midollo Osseo, Cremona; F. Leoni, S. Ciolli, Div. Ematologia, Firenze; L. Deriu, Div. Ematologia, Latina; F. De Cataldo, F. Baudo, Div. Ematologia Talamona, Niguarda (MI); A. Spada, Sez. Autonoma di Ematologia T.E.R.E., Napoli; R. De Biase, E. Miraglia, Div. Ematologia Ospedale Nuovo Pellegrini, Napoli; B. Rotoli, Div. Ematologia II Facoltà, Napoli; A. Gabbas, G. Latte, Sez. Ematologia Clinica, Nuoro; F. Caronia, S. Vasta, Div. Ematologia Osp. V. Cervello, Palermo; P. Citarrella, M. Tambone Reyes, Cattedra di Ematologia, Palermo; E. Ascari, R. Invernizzi, Clinica Medica II, Pavia; M. Martelli, A. Tabilio, 1st. Clinica Medica Generalee Terapia Medica I, Cattedra di Ematologia, Perugia; G. Lucarelli, G. Sparaventi, Div. di Ematologia di Muraglia, Pesaro; G. Torlontano, G. Recchia, Div. di Ematologia, Pescara; F. Ricciuti, A. Dinota, Div. Ematologia, Potenza; F. Nobile, Div. Ematologia, Reggio Calabria; G. Leone, 1st. Semeiotica Medica, Div. Ematologia, Università Cattolica, Roma; L. Annino, A. Ferrari, Cattedra di Ematologia, Università “La Sapienza”, Roma; A. De Laurenzi, N. Petti, Div. Ematologia, Osp. S. Camillo, Roma; G. Papa, E. Stipa, Cattedra di Ematologia, Osp. S. Eugenio, Roma; M. Carotenuto, S. Ladogana, Div. di Ematologia, S. Giovanni Rotondo (FG); M. Baccarani, G. Fasola, Cattedra di Ematologia, Udine

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