Can Heparin-Based Therapy in Children Be Monitored on Samples Drawn Through Ports? An Analysis From Clinical Trials Data,

Based on preliminary data, children clear heparins more rapidly than adults, and thus most pediatric hematologists monitor heparin therapy. Many pediatric deep vein thrombosis patients have indwelling central venous lines (CVLs) due to co-morbid conditions and patients and clinicians desire to use these CVLs for blood sampling. Standard protocols are used to flush and clear CVLs prior to sample collection, but validated approaches to exclude contamination of heparin in dwell-volume (i.e., hep-lock) from systemic anticoagulant have not been established. Aims: This study was conducted to determine the accuracy of heparin monitoring in samples collected from CVLs. Methods: Anticoagulant effects of unfractionated heparin (UH) and dalteparin low molecular weight heparin (D) were determined by assay of anti-IIa activity, anti-Xa activity and the ratio of the two using chromogenic assays (Biophen). Normal pooled plasma was spiked with 2 U/mL of either drug and dilutions were made to 1.5, 1, 0.75, 0.5, 0.25 and 0.1 U/mL in normal pooled plasma. The assays and ratios were applied to plasma samples obtained by standard protocol from CVLs or peripheral venipuncture in two separate clinical trials. Results: Intra-assay CV for anti-IIa was 14.2 and 13.3% for UH and D, respectively; intra-assay CV for anti-Xa was 8.3 and 2.8% for UH and D, respectively. The ratio of anti-IIa to anti-Xa activity for UH was > 0.75 at all concentrations, while the ratio of anti-IIa to anti-Xa for D was < 0.5 when anti-Xa was within the therapeutic range of 0.5–1.0 U/mL, but overlapped with UH at concentrations ≥ 1.5 U/mL and ≤ 0.25 U/mL. In trial 1, DAVINCI, 4/26 (15.4% of) samples drawn from CVLs with therapeutic anti-Xa activity had ratios > 0.5 suggestive of UH contamination, while 0/8 peripherally drawn samples had ratios in that range. In trial 2, 5/26 (19.2% of) patient samples drawn from CVLs had ratios > 0.5. Conclusions: An anti-IIa/anti-Xa ratio < 0.5 is specific for uncontaminated D effect when anti-Xa is within the therapeutic range. However, without measuring ratios 15–20% of CVL samples used to monitor D will overestimate therapeutic response. Therefore, we favor peripherally drawn samples in order to reliably monitor anticoagulation in children.

Manco-Johnson:Easai: Research Funding. Goldenberg:Easai: Research Funding.