Antithrombin Iii Supplementation in Childhood Acute Lymphoblastic Leukemia Treated With L-Asparaginase

Abstract

The change of plasma antithrombin III (AT) levels after supplementation of AT concentrates was examined in ALL children with acquired AT deficiency following L-asparaginase (ASP) administration. The patients received AT concentrates of 34.5 +/- 7.6 U/kg. The increase of plasma AT activity and antigen was 2.07 +/- 0.62% and 0.70 +/- 0.16 mg/dL per unit AT infused per kilogram of body weight, respectively. The activity decreased to 62.0 +/- 7.7% of the peak values by 48 hours after supplementation. The administration of AT concentrates constantly increased the plasma AT activity in ALL children treated with ASP, which may minimize the acquired prothrombotic state.

Population pharmacokinetics of human antithrombin concentrate in paediatric patients

“…The relationship between UFH and AT was linear, demonstrating increased clearance with increasing UFH doses. The values obtained in our dataset were similar to those reported previously [17,22,23]. Regular monitoring of AT levels should occur when UFH is administered concurrently.…”

“…The published dosing recommendations from the manufacturer are as follows: [desired AT level (%) – baseline AT level (%)] × body weight (kg)] divided by 1.4 = units of AT required . As this formula was based on data from adults, paediatric dosing has been often reported in units kg –1 per dose for initial doses, and subsequent doses adjusted based on patient response . Formal assessments of AT in paediatric patients have focused on attainment of goal concentrations but have never evaluated its pharmacokinetics or covariates which could potentially be important for optimizing dosing strategies.…”

Capped antithrombin III dosing is cost effective in the management of asparaginase‐associated thrombosis

“…Matsuzaki and colleagues previously published data on peak ATIII concentrations in pediatric patients receiving asparaginase. In a notably younger population of seven patients (age 1–16 years; weight 11–60 kg), peak levels were obtained five minutes following an ATIII infusion and ranged from 119% to 191% . Peak levels in our study were to be drawn 15 minutes post‐infusion as a compromise between the 20 minutes recommended in the Thrombate III package insert and the results of the Matsuzaki trial, which provides a quantified comparison of peak levels in a similar population.…”

“…In a notably younger population of seven patients (age 1-16 years; weight 11-60 kg), peak levels were obtained five minutes following an ATIII infusion and ranged from 119% to 191%. 9 Peak levels in our study were to be drawn 15 minutes post-infusion as a compromise between the 20 minutes recommended in the Thrombate III package insert and the results of the Matsuzaki trial, which provides a quantified comparison of peak levels in a similar population. The peak levels obtained in our study ranged slightly lower from 88% to 147%, which may be explained by the difference in timing of the level or differences in this patient population (BMI).…”