Comparison of routine laboratory measures of heparin anticoagulation for neonates on extracorporeal membrane oxygenation

Abstract

Our objective was to determine the best measure of heparin anticoagulation in neonatal patients on extracorporeal membrane oxygenation. Activated clotting time (ACT), activated partial thromboplastin time (aPTT), and antifactor Xa levels, along with corresponding heparin infusion rates and heparin bolus volumes, were collected from neonates receiving ECMO at our institution from 2008 to 2013. After natural log transformation of antifactor Xa, ACT, and aPTT, overall correlations between antifactor Xa levels and either ACT or aPTT and correlations between these tests and heparin infusion rates were evaluated using linear mixed models that accounted for both within- and between-patient correlations. Twenty-six neonates with an average weight of 3.4 kg (standard deviation .7) had a total of 27 separate ECMO runs during the study period. Within each patient, ACT (r = .40, p < .0001) and aPTT (r = .48, p < .0001) were both directly correlated with antifactor Xa levels. In contrast, between patients, only aPTT maintained a direct correlation with antifactor Xa (r = .61, p = .07), whereas ACT showed a statistically significant inverse correlation with antifactor Xa (r = -.48, p = .04). Compared with ACT, aPTT is more consistently reflective of the anticoagulation status both within each patient on ECMO and between patients treated with ECMO. Future efforts to develop standardized heparin infusion algorithms for patients on ECMO should consider using aPTT levels to monitor anticoagulation.

Figure 1.

Anticoagulation algorithm. ACT, activated clotting time; aPTT, activated partial thromboplastin time; ATIII, antithrombin; anti-Xa, unfractionated antifactor Xa; DIC, disseminated intravascular coagulopathy; FFP, fresh-frozen plasma; UFH, unfractionated heparin.

Figure 2.

Changes in coagulation markers over time on ECMO. These curves were estimated by averaging patient-specific changes in anticoagulation measures and heparin infusion rates over time on ECMO across all patients. Over the entire ECMO run for all patients, there was an average increase in the heparin infusion rate of .19 units/kg/h (95% confidence interval, .11–.26) with aPTT and ACT decreasing by .48 seconds (.18–.78 seconds) and .12 seconds (.02–.22 seconds) each hour, respectively (p < .05). Most of these changes occurred within the first 48 hours. After 48 hours, ACT had a significant increase over time (.14 seconds, .00–.27 seconds, p = .047), whereas aPTT had no significant change. There was no significant change in the antifactor Xa levels over the duration of ECMO (p = .76). ECMO, extracorporeal membrane oxygenation; ACT, activated clotting time; aPTT, activated partial thromboplastin time; Xa, antifactor Xa level; UFH, unfractionated heparin.

Figure 3.

Correlations between measures of anticoagulation in neonatal patients on ECMO receiving heparin. Within-patient correlations between ACT (A) or aPTT (B) and antifactor Xa are displayed in A and B; these within-patient correlations describe the association between changes in these factors over time in each patient during their ECMO run. In an individual patient, changes in ACT and aPTT both reflect similar changes in antifactor Xa levels. Between-patient correlations between ACT (C) or aPTT (D) and antifactor Xa are displayed in C and D; the between-patient correlations measure whether high values of one factor are reflective of high values of the other factor across patients on EMCO. Across patients on ECMO, higher ACT measures do not reflect higher antifactor Xa levels, whereas for aPTT, higher aPTT levels are reflective of higher antifactor Xa levels. ECMO, extracorporeal membrane oxygenation; ACT, activated clotting time; aPTT, activated partial thromboplastin time.