title: Pegasparaginase treatment alters thrombin generation by modulating the protein C and S system in acute lymphoblastic leukaemia/lymphoma.
abstract: Paediatric patients with acute lymphoblastic leukaemia/lymphoma treated with pegasparaginase are at an increased risk of thrombosis. We evaluated changes in thrombin generation in the presence and absence of thrombomodulin using paired plasma samples collected from paediatric patients treated with pegasparaginase. Postpegasparaginase samples were significantly less sensitive to reductions in thrombin generation in the presence of thrombomodulin compared with prepegasparaginase, suggesting reduced protein C and S activity. This corresponded to a significant decrease in protein C and protein S antigen. Alterations in the protein C and S pathway may contribute to the increased risk of thrombosis in patients treated with pegasparaginase.
authors.affiliation: aDepartment of Pediatrics, Division of Hematology and Oncology, University of Utah School of Medicine bDepartment of Pathology and ARUP Laboratories Institute for Clinical and Experimental Pathology, University of Utah School of Medicine cHuntsman Cancer Institute, University of Utah dHigh Risk Pediatric Cancer Clinic, University of Utah eDepartment of Medicine and Program in Molecular Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA.
authors.forename: Jack H
authors.initials: JH
authors.lastname: Staddon
authors.forename: Kristi J
authors.initials: KJ
authors.lastname: Smock
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Schiffman
authors.forename: Mark N
authors.initials: MN
authors.lastname: Fluchel
authors.forename: Michael E
authors.initials: ME
authors.lastname: Engel
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Weyrich
authors.forename: Robert A
authors.initials: RA
authors.lastname: Campbell
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D011486:Protein C / Q000378:metabolism*; D017293:Protein S / Q000378:metabolism*; D013917:Thrombin / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D011486:Protein C; D017293:Protein S; D013917:Thrombin; D001215:Asparaginase