Evidence of a hypercoagulable state in patients with acute lymphoblastic leukemia treated with low dose of E. coli L-asparaginase: a GIMEMA study.
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.
Leone
G
G
Istituto di Semeiotica Medica, Università Cattolica, Roma, Italy.
Gugliotta
L
L
Mazzucconi
M G
MG
De Stefano
V
V
Belmonte
M M
MM
Dragoni
F
F
Specchia
G
G
Centra
A
A
Gamba
G
G
Camera
A
A
D000293:Adolescent; D000328:Adult; D001215:Asparaginase / Q000008:administration & dosage / Q000009:adverse effects*; D001778:Blood Coagulation Disorders / Q000139:chemically induced*; D001779:Blood Coagulation Factors / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy*; D012680:Sensitivity and Specificity; D013917:Thrombin / Q000096:biosynthesis*; D013924:Thrombophlebitis / Q000139:chemically induced / Q000453:epidemiology
D001779:Blood Coagulation Factors; D013917:Thrombin; D001215:Asparaginase