title: Antithrombin III infusion suppresses the hypercoagulable state in adult acute lymphoblastic leukaemia patients treated with a low dose of Escherichia coli L-asparaginase. A GIMEMA study.
abstract: Thrombotic events have been reported in acute lymphoblastic leukaemia patients, especially during or after L-asparaginase administration. A so-called L-asparaginase associated coagulopathy has been well recognized, being characterized by a hypercoagulable state (decrease of antithrombin III, plasminogen, protein C, protein S and increase of prothrombin fragment F1 + 2, thrombin-antithrombin complexes and fibrinopeptide A). The aim of this study was to determine whether the supplementation of antithrombin III (AT-III) concentrates could improve the L-asparaginase associated coagulopathy, thereby blocking the activation of the haemostatic system. In 25 adult patients with acute lymphoblastic leukaemia (M 19, F6, mean age 34 years) antithrombin III (AT-III) concentrates were administered at daily doses of 50 U/kg for 10 consecutive days from the beginning of L-asparaginase therapy (6,000 U/m2/day s.c. for 7 days), given according to the GIMEMA ALL 0288 trial. A marked increase of antithrombin III was recorded on days IV-VIII-XI (P < 0.001). No changes in protein C, protein S, plasminogen, alpha 2-antiplasmin, factor VII and platelet count were observed and there was no increase in markers of hypercoagulability. There was no evidence of disseminated intravascular coagulation. In conclusion, AT-III concentrate supplementation during L-asparaginase therapy, by the achievement of high levels of antithrombin III, is associated with a lack of activation of the haemostatic system and appears to overcome the complex coagulopathy associated with L-asparaginase.
authors.affiliation: Haematology Department, University La Sapienza, Rome, Italy.
authors.forename: M G
authors.initials: MG
authors.lastname: Mazzucconi
authors.forename: L
authors.initials: L
authors.lastname: Gugliotta
authors.forename: G
authors.initials: G
authors.lastname: Leone
authors.forename: F
authors.initials: F
authors.lastname: Dragoni
authors.forename: M M
authors.initials: MM
authors.lastname: Belmonte
authors.forename: V
authors.initials: V
authors.lastname: De Stefano
authors.forename: A
authors.initials: A
authors.lastname: Chistolini
authors.forename: S
authors.initials: S
authors.lastname: Tura
authors.forename: F
authors.initials: F
authors.lastname: Mandelli
mesh_terms: D000293:Adolescent; D000328:Adult; D000990:Antithrombin III / Q000008:administration & dosage / Q000627:therapeutic use*; D001215:Asparaginase / Q000009:adverse effects* / Q000627:therapeutic use; D001778:Blood Coagulation Disorders / Q000188:drug therapy* / Q000209:etiology; D003520:Cyclophosphamide / Q000627:therapeutic use; D004926:Escherichia coli / Q000201:enzymology*; D005167:Factor VII / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010958:Plasminogen / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000188:drug therapy*; D011486:Protein C / Q000378:metabolism; D017293:Protein S / Q000378:metabolism; D000979:alpha-2-Antiplasmin / Q000378:metabolism
chemical_list: D011486:Protein C; D017293:Protein S; D000979:alpha-2-Antiplasmin; D003520:Cyclophosphamide; D000990:Antithrombin III; D005167:Factor VII; D010958:Plasminogen; D001215:Asparaginase