Correlation of UFH Measures of Effect with Protamine Titration in Children

  • Geoff Lane, Australia
  • Ms Fiona Newall, The Royal Children's Hopsital, Australia
  • V Ignjatovic, The University of Melbourne, Murdoch Children's Research Institute and The Royal Children's Hospital, Australia
  • L Johnston, The University of Melbourne and Queens University Belfast
  • R Summerhayes, Australia
  • P Monagle, The University of Melbourne; Murdoch Children's Research Institute; The Royal Children's Hospital, Australia
  • Therapeutic ranges for UFH therapy are based on measures of UFH effect corresponding to a UFH concentration of 0.2 to 0.4IU/mL by protamine titration (Pr.T.). In adults, this corresponds to an anti-Xa assay of 0.35-0.7IU/mL. Such a reference range has never been validated in children. This study aimed to determine the strength of correlation between Pr.T., APTT, anti-Xa and TCT (6 NIH units) in plasma collected from children given a 75-100IU/kg bolus of UFH. Blood samples were collected from children aged <16 years (n=64) at 15, 30, 45 and 120 minutes post UFH. Agreement between assays was determined using Lin's Correlation Coefficient. Correlation coefficients between Pr.T. and APTT, anti-Xa and TCT were 0.49, 0.49 and 0.47, respectively across the whole population. 47 anti-Xa assays were within 0.35 to 0.7IU/mL. Table 1 describes the agreement between anti-Xa assays of 0.35 to 0.7IU/mL with therapeutic range determined by Pr.T.
    Thus for the majority of time points (34/47) for which the anti Xa assay was therapeutic, the gold standard Pr.T. was supratherapeutic. APTT and TCT were similarly lacking agreement with Pr.T. Given that, in adults, the rationale for using antiXa, APTT or TCT as a monitoring test for UFH is based on the correlation with Pr.T., this lack of correlation in children suggests that these assays are not ideal for monitoring UFH in paediatrics. Further clinical outcome studies are required to determine optimal methods of monitoring UFH in children.