Retrospective cohort study comparing activated partial thromboplastin time versus anti‐factor Xa activity nomograms for therapeutic unfractionated heparin monitoring in pediatrics

Abstract

To cite this article: Trucco M, Lehmann CU, Mollenkopf N, Streiff MB, Takemoto CM. Retrospective cohort study comparing activated partial thromboplastin time versus anti-factor Xa activity nomograms for therapeutic unfractionated heparin monitoring in pediatrics. J Thromb Haemost 2015; 13: 788-94. Summary. Background: Unfractionated heparin (UFH) is widely used to treat thromboembolic disease, but monitoring in children is challenging. Both activated partial throm-boplastin time (aPTT) and anti-factor Xa activity (anti-Xa) are utilized, but a comparison of dosing nomograms has not been reported in pediatrics. Objective: To compare the performance of aPTT and anti-Xa for UFH monitoring in pediatric patients. Design/methods: A retrospective cohort study was conducted in patients ≤ 21 years old treated with UFH at Johns Hopkins Hospital from January 2009 to May 2011. For monitoring, an aPTT nomogram was used for the initial 15 months, and an anti-Xa nomogram was used for the subsequent 12 months. Clinical characteristics, laboratory data and outcomes were analyzed. Results: Thirty-four patients were monitored with aPTT and 26 patients with anti-Xa. There was no significant difference in median time to therapeutic range (11.6 h aPTT, 95% CI = 6.0-17.0; 9.9 h anti-Xa, 95%CI = 7.3-20.7) or per cent of patients achieving therapeutic measurements at 24 (79% aPTT, 95%CI = 62-91; 73% anti-Xa, 95%CI = 52-88) and 48 h (88% aPTT, 95%CI = 73-97; 96% anti-Xa, 95%CI = 80-100). However, anti-Xa measurements were more frequently therapeutic than aPTT (74% [95% CI = 69-78] vs. 54% [95%CI = 50-59]). Variance between anti-Xa and aPTT measurements was high (R 2 = 0.236). No significant difference was seen in bleeding incidence (9% aPTT, 95%CI = 2-24; 15% anti-Xa, 95%CI = 4-35). Conclusion: The time to achieve therapeutic measures and bleeding outcomes were not significantly different between anti-Xa and aPTT nomograms. However, a small study size limits the power to detect clinically relevant differences. The results warrant larger prospective studies of UFH monitoring in children with thromboembolic disease.

Deep vein thrombosis in pediatric patients

“…Increased dosing is needed in neonates due to decreased levels of antithrombin, and in children less than 1 year of age due to increased heparin binding to non‐antithrombin proteins. UFH can be monitored using the activated thromboplastin time (activated partial thromboplastin [aPTT]) or antifactor Xa assay, although studies have shown increased time in the therapeutic range when using the antifactor Xa assay . Heparin‐induced thrombocytopenia (HIT) is a rare, but serious side effect, which occurs in 1–2% of children exposed to heparin due to the development of antibodies against platelet factor 4/heparin complex .…”

“…UFH can be monitored using the activated thromboplastin time (activated partial thromboplastin [aPTT]) or antifactor Xa assay, although studies have shown increased time in the therapeutic range when using the antifactor Xa assay. 44 Heparininduced thrombocytopenia (HIT) is a rare, but serious side effect, which occurs in 1-2% of children exposed to heparin due to the development of antibodies against platelet factor 4/heparin complex. 45 Treatment includes stopping all heparin products and starting a nonheparin anticoagulant.…”

Rationale and design of a phase III safety trial of idarucizumab in children receiving dabigatran etexilate for venous thromboembolism

“…33 However, bleeding rates of up to 24% were reported in critically ill children receiving unfractionated heparin and who were at increased risk of bleeding. 34,35 The current management of symptomatic bleeding associated with dabigatran has some similarities to that observed in patients taking VKA, such as the cessation of anticoagulant treatment and the use of supportive care guided towards hemodynamic stabilization. In addition, hemodialysis may represent an option to expedite the removal of systemic dabigatran.…”

Anticoagulants in children and adolescents

“…15,16 Furthermore, several studies have also demonstrated discrepancies between the aPTT and the anti-Xa assay. [15][16][17] Assay issues aside, what is clear is that there is a high degree of interpatient and even intrapatient variability in dosing, further complicating management. 18 Furthermore, heparin therapy can result in HIT, a serious and, in pediatrics, often under-recognized phenomenon, which has the potential to lead to severe consequences in an already vulnerable population of patients.…”