Antithrombin dosing guidelines in children underestimate dose needed for plasma level increase

Abstract

AIMS & OBJECTIVES: Antithrombin (AT) is a co-factor in the coagulation cascade and facilitates the action of heparin as an anticoagulant. AT concentrate (ATC) dosing guidelines vary, but most commonly suggest that each unit of ATC per kg body-weight (BWT) increases the plasma AT level by 1.5% to 2.2%. We aimed to establish a dosing recommendation dependent on age and disease state. METHODS: A retrospective analysis over a period of 5 years. We calculated the increase any respective ATC dose achieved, indexed by BWT, and performed a multivariable analysis to establish independent factors associated with the effectiveness of ATC. RESULTS: The effect of 562 doses of ATC on plasma AT levels administered to 155 patients, of which 414 (73.7%) ATC doses administered during extra-corporeal life support (ECLS) treatment, were analysed. For all patients each unit of ATC/kg increased plasma AT level by 0.86% (standard deviation [SD] 0.47%). Plasma AT level increase was influenced by body-weight (increase of 0.76% [IQR 0.6 -0.92] for patients <5kg; 1.38% [IQR 1.11-2.10] for >20 kg), disease state (liver failure having the poorest AT increase) and whether patients were treated with extracorporeal circulatory support (less AT increase on ECLS). Heparin dose at the time of administration did not influence with amount of change in AT level. CONCLUSIONS: Current ATC dosing guidelines overestimate the effect on plasma AT level in critically ill children. Current recommendations result in under-dosing of ATC administration. Age, disease state, and ECLS should be taken into consideration when administering ATC.L6347732872021-04-21 <br />