aPTT in children receiving UFH: time for a change?

Unfractionated heparin (UFH) remains an important therapeutic modality for anticoagulation in children. Its short half-life and easy reversibility with protamine sulfate make it an attractive option in critically ill children. Although initially described as a screening tool for hemophilia, the aPTT is a global hemostatic assay that reflects the integrity of the intrinsic and common pathways of the in vitro coagulation cascade and is commonly used to monitor UFH. In a landmark publication in 1972, Basu et al demonstrated that the risk of recurrent thrombosis in adults receiving heparin could be significantly reduced by aiming for a 1.5 to 2.5 times prolongation of the aPTT. A subsequent cohort study by Andrew et al documented a 73% agreement between aPTT and anti-Xa activity in 52 children receivingUFH therapy (r5 0.51), and the therapeutic range of 1.5 to 2.5 times baseline was extrapolated for children. Over time, however, it has become apparent that the aPTT is affected by several preanalytical, analytical, and biological variables, and current guidelines recommend that the therapeutic aPTT range corresponds to an anti-Xa of 0.35 to 0.7 U/mL. Recent studies have documented poor agreement between the 2 assays (r: 0.08-0.27), with the aPTT frequently overestimating the heparin effect compared with anti-Xa. In the current article, the authors report post hoc analysis on laboratory data collected during a parallel cohort, randomized, double-blinded controlled study comparing 2 dosing protocols of UFH to prevent thromboembolism in children undergoing cardiac catheterization (HEART CAT). The primary clinical outcomes of the study were previously published and did not demonstrate a significant difference in thrombosis or bleeding between high-dose and low-dose UFH. aPTT, anti-Xa, and ACTs were obtained at baseline and 30, 60, and 90 minutes after heparin bolus; in total, 492 blood samples were collected from 149 subjects. Although all 3 assays discriminated well between high-dose and low-dose UFH, there was poor correlation between the assays. Congruent with previous reports, the aPTT frequently overestimated the UFH effect reported by anti-Xa and was supratherapeutic for all measured time points in both protocols (see figure). In the high-dose arm (100-U/kg bolus followed by continuous infusion), the anti-Xa was supratherapeutic initially, but became therapeutic by 90minutes. In the low-dose arm (50-U/kg bolus without continuous infusion), the anti-Xa was therapeutic initially but rapidly became subtherapeutic. The authors therefore suggest a 75-U/kg bolus in pediatric subjects undergoing cardiac catheterization procedures. They also conclude that that the aPTT was overly sensitive to heparin effect in this cohort and suggest using anti-Xa, with the ACT recommended as a comparably Time course of anti-Xa and aPTT values (median, 95% confidence interval) comparing high-dose (100-U/kg bolus followed by continuous infusion) vs low-dose (50-U/kg bolus without continuous infusion) UFH dosing protocols. Yellowshaded bars indicate therapeutic ranges. This figure has been adapted from Figure 1 in the article by Hanslik et al that begins on page 2091. Professional illustration by Patrick Lane, ScEYEnce Studios.