The Impact of Dextran Sulfate on Anti-Xa Assay Outcomes after Unfractionated Heparin Reversal by Excessive Protamine.

Currently, the anti-Xa assay is the "gold standard" for monitoring heparin activity; however, dextran sulfate (DS) addition to analytical reagents can lead to overestimated heparin activity following unfractionated heparin (UFH) reversal by protamine (Pr), often leading to improper UFH management. We investigated the impact of DS on anti-factor Xa assay outcomes after UFH was reversed by excessive Pr. Normal pooled plasma samples were spiked with UFH and Pr to prepare samples with varying Pr to UFH (P: H) ratios of different UFH concentrations. A chromogenic method was used to detect anti-Xa activity using two reagents: HemosIL liquid anti-Xa with DS (HemosIL) and STA liquid anti-Xa without DS (STA). When the P: H ratio was ≥ 1.0, i.e., Pr was equal or in excess, anti-Xa activity was detected by the HemosIL reagent, and did not decrease as expected, with dose-dependent effects with increasing UFH concentrations, while anti-Xa activity using STA reagent was almost undetectable. Meanwhile, both APTT and TT were within reference ranges, indicating that UFH had been completely neutralized. Therefore, when using HemosIL reagent (with DS) to detect anti-Xa activity from UFH reversal by excessive Pr, clinicians must be aware of potential DS interference and consider alternative monitoring strategies to accurately assess anticoagulant status. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-025-01971-7.