Different profile of thrombin generation in children with acute lymphoblastic leukaemia treated with native or pegylated asparaginase: A cohort study.
Asparaginase (Asp) and corticosteroid (CS) treatment in patients with acute lymphoblastic leukaemia (ALL) is associated with an increased risk of thrombotic events.



Characterization of global haemostatic phenotypes of patients with ALL during Asp therapy.



Thrombin generation (TG) was monitored in platelet-poor plasma of 56 children treated for a B lineage ALL (36 with native, 20 with PEG Asp) using 1 pM tissue factor and 4 μM phospholipids, with and without thrombomodulin. Protein C activity (PC), free protein S (PS), antithrombin (AT) and fibrinogen levels were also measured.



Elevated endogenous thrombin potential (ETP) and peak of TG were noted at diagnosis, throughout the Induction phase and Late Intensification but was significantly less for PEG than for native Asp (P < 0.001), while age, sex, type of corticosteroid during Induction and molecular response had no significant effect. The reduction of ETP after addition of thrombomodulin was significantly lower in ALL children compared with that in controls, suggesting impairment in PS/PC pathway. Three patients experienced thrombosis: two treated with native and one with PEG Asp. The two patients with native Asp had, at the time of thrombosis, a prothrombotic profile.



Treatment with Asp, in combination with CS, enhances TG in children with ALL, more significantly with native than PEG Asp, which is present early at diagnosis, persists during Induction and reappears during Late Intensification. This is consistent with the high incidence of thrombotic events described during these phases of therapy. The less pronounced effect of PEG Asp remains to be elucidated.
Laboratory of hematology, CHU Brugmann, LHUB-ULB, ULB Université libre de Bruxelles, Brussels, Belgium.
Laurence
L
Rozen
Laboratory of hematology, CHU Brugmann, LHUB-ULB, ULB Université libre de Bruxelles, Brussels, Belgium.
Denis
D
Noubouossie
Hematology-Oncology Unit, Hôpital Universitaire des Enfants Reine Fabiola, ULB Université libre de Bruxelles, Brussels, Belgium.
Laurence
L
Dedeken
Hematology-Oncology Unit, Hôpital Universitaire des Enfants Reine Fabiola, ULB Université libre de Bruxelles, Brussels, Belgium.
Sophie
S
Huybrechts
Hematology-Oncology Unit, Hôpital Universitaire des Enfants Reine Fabiola, ULB Université libre de Bruxelles, Brussels, Belgium.
Phu Quoc
PQ
Lê
Hematology-Oncology Unit, Hôpital Universitaire des Enfants Reine Fabiola, ULB Université libre de Bruxelles, Brussels, Belgium.
Alina
A
Ferster
Laboratory of hematology, CHU Brugmann, LHUB-ULB, ULB Université libre de Bruxelles, Brussels, Belgium.
Anne
A
Demulder
D000293:Adolescent; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001215:Asparaginase / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006487:Hemostasis; D006801:Humans; D007223:Infant; D008297:Male; D011092:Polyethylene Glycols / Q000009:adverse effects*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D011379:Prognosis; D013917:Thrombin / Q000378:metabolism*; D013927:Thrombosis / Q000139:chemically induced / Q000175:diagnosis* / Q000378:metabolism
D000970:Antineoplastic Agents; D011092:Polyethylene Glycols; C042705:pegaspargase; D013917:Thrombin; D001215:Asparaginase
acute lymphoblastic leukaemia; asparaginase; coagulation; haemostatic potential; thrombin generation