Different profile of thrombin generation in children with acute lymphoblastic leukaemia treated with native or pegylated asparaginase: A cohort study: Rozen et al.
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| Titel: | Different profile of thrombin generation in children with acute lymphoblastic leukaemia treated with native or pegylated asparaginase: A cohort study: Rozen et al. |
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| Autoren: | Rozen, Laurence, Noubouossié, Denis, Dedeken, Laurence, Huybrechts, Sophie, Lê, Phu Quoc, Ferster, Alina, Demulder, Anne |
| Quelle: | Pediatric Blood & Cancer. 64:294-301 |
| Verlagsinformationen: | Wiley, 2016. |
| Publikationsjahr: | 2016 |
| Schlagwörter: | Male, haemostatic potential, acute lymphoblastic leukaemia, Adolescent, Pédiatrie, Antineoplastic Agents, Precursor Cell Lymphoblastic Leukemia-Lymphoma -- complications -- drug therapy -- metabolism, Polyethylene Glycols, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Polyethylene Glycols -- adverse effects, Asparaginase -- adverse effects, Asparaginase, Humans, coagulation, Preschool, Child, Hemostasis, Thrombosis -- chemically induced -- diagnosis -- metabolism, Thrombin, Antineoplastic Agents -- adverse effects, Infant, Thrombosis, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Thrombin -- metabolism, asparaginase, Prognosis, 3. Good health, Cancérologie, thrombin generation, Child, Preschool, Female, Hématologie, Follow-Up Studies |
| Beschreibung: | 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. |
| Publikationsart: | Article |
| Dateibeschreibung: | 1 full-text file(s): application/pdf |
| Sprache: | English |
| ISSN: | 1545-5009 |
| DOI: | 10.1002/pbc.26228 |
| Zugangs-URL: | https://pubmed.ncbi.nlm.nih.gov/27605400 https://onlinelibrary.wiley.com/doi/abs/10.1002/pbc.26228 https://www.ncbi.nlm.nih.gov/pubmed/27605400 https://difusion.ulb.ac.be/vufind/Record/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/242209/Details |
| Rights: | Wiley Online Library User Agreement |
| Dokumentencode: | edsair.doi.dedup.....5a653b8bc4dd9ebdc3e9b34047d8bb8e |
| Datenbank: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstract: | 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. |
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| ISSN: | 15455009 |
| DOI: | 10.1002/pbc.26228 |