title: Fresh frozen plasma has no beneficial effect on the hemostatic system in children receiving L-asparaginase.
abstract: L-Asparaginase (ASP), a chemotherapeutic agent used in the treatment of children with acute lymphoblastic leukaemia (ALL), is linked to thromboembolic complications secondary to an acquired deficiency of antithrombin III (ATIII). Fresh frozen plasma (FFP) is used to prevent and/or treat thrombotic complications in these children. However, the effect of FFP on plasma concentrations of ATIII and biochemical markers of activation of coagulation has never been tested. In this study, FFP (20 ml/kg) was administered to eight children with ALL receiving ASP in the consolidation phase of their treatment. Plasma samples were drawn pre-infusion, and following infusion at 1, 24, and 48 hr. Prior to the FFP infusions, plasma concentrations of prothrombin, fibrinogen, alpha 2-macroglobulin, heparin cofactor II, protein C, and protein S were similar to levels in healthy children. Only plasma concentrations of ATIII were significantly decreased (0.55 U/ml). Following FFP infusions, there was no statistical or clinically important increase in plasma concentrations of any coagulation protein at any time point. Pre-infusion plasma concentrations of markers of endogenous thrombin generation (thrombin-antithrombin III complexes (TAT)) and activation of the fibrinolytic system in response to activation of the coagulation system (D-dimer levels) were significantly increased. However, FFP had no statistical or clinically important effect on concentrations of these markers. We conclude that FFP administration for the prevention and treatment of acquired ATIII deficiency secondary to ASP has no demonstrable benefit on plasma levels of coagulation proteins and is unlikely to be of clinical benefit.
authors.affiliation: Department of Paediatrics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: J M
authors.initials: JM
authors.lastname: Halton
authors.forename: L G
authors.initials: LG
authors.lastname: Mitchell
authors.forename: P
authors.initials: P
authors.lastname: Vegh
authors.forename: M
authors.initials: M
authors.lastname: Eves
authors.forename: M E
authors.initials: ME
authors.lastname: Andrew
mesh_terms: D000293:Adolescent; D000990:Antithrombin III / Q000032:analysis; D020152:Antithrombin III Deficiency; D001215:Asparaginase / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D001777:Blood Coagulation / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D005340:Fibrinogen / Q000032:analysis; D006487:Hemostasis / Q000187:drug effects / Q000502:physiology*; D015844:Heparin Cofactor II / Q000032:analysis; D006801:Humans; D010949:Plasma / Q000502:physiology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy; D011486:Protein C / Q000032:analysis; D017293:Protein S / Q000032:analysis; D011516:Prothrombin / Q000032:analysis; D000511:alpha-Macroglobulins / Q000032:analysis
chemical_list: D011486:Protein C; D017293:Protein S; D000511:alpha-Macroglobulins; D015844:Heparin Cofactor II; D000990:Antithrombin III; D011516:Prothrombin; D005340:Fibrinogen; D001215:Asparaginase