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.

Personal practice: How we manage the risk of bleeding and thrombosis in children and young adults with acute lymphoblastic leukaemia

“…Prophylactic FFP/cryoprecitate No effect on haemostatic parameters (Halton et al, 1994;Mitchell et al, 1995;Nowak-Gottl et al, 1995). Single study suggesting a possible benefit in patients at high risk of thrombosis (Abbott et al, 2009) Restrict use to therapeutic transfusions Prophylactic platelet transfusions prior to lumbar puncture…”

“…FFP also did not influence thrombin generation, plasmin/a2 antiplasmin complex or enhanced D-dimer formation. Halton et al (1994) administered 20 ml/kg FFP to children with ALL receiving asparaginase during the consolidation phase of treatment. Following the infusions there was no statistical or clinically important increase in plasma concentrations of coagulation proteins at any time point.…”

Emergency correction of coagulation for mitral valve replacement in an orally anticoagulated 17-year-old patient with pronounced hepatic dysfunction

“…They found that even a dose of 12 ml/kg of fresh frozen plasma did not correct the hemostatic defects in 6 out of 10 patients, whereas the administration of PCC followed by therapy with factor VII concentrate resulted in normalisation of the prothrombin time in all but one of 11 patients. Other authors [5,6] have investigated the amount of fresh frozen plasma necessary to correct hemostatic defects in patients with oncologic disorders. Even doses of up to 20 ml/kg showed no statistical or clinically satisfying increase of coagulation proteins.…”

Comparison of the anticoagulant effect of a direct thrombin inhibitor and a low molecular weight heparin in an acquired antithrombin deficiency in children with acute lymphoblastic leukaemia treated with l‐asparaginase: an in vitro study

“…As the mechanism for thrombosis may be related to the acquired AT deficiency, two studies have assessed correction of AT levels as a therapeutic intervention. The first study assessed the administration of fresh frozen plasma and showed that the correction of the acquired AT deficiency is not achieved using standard dosages (Halton et al, 1994). In a recent randomised controlled clinical trial, prophylactic administration of AT concentrate showed a trend to efficacy (Mitchell et al, 2003b).…”