Impact of exogenous antithrombin on low molecular weight heparin anti-Xa activity assays in a pediatric and young adult leukemia and lymphoma cohort with variable antithrombin levels

Background: Low molecular weight heparin (LMWH) remains the most commonly prescribed pediatric anticoagulant. There is debate whether LMWH anti-Xa assays with or without exogenous antithrombin (AT) best reflect anticoagulation effect, and how much discrepancy exists between assay types. Objectives: We assessed the effect of variable AT activity on LMWH anti-Xa levels in plasma samples from anticoagulated pediatric and young adult acute lymphoblastic leukemia and lymphoma (ALL/L) patients, using two instruments and their commercial kits with and without exogenous AT (ie, four platforms). Methods: We analyzed LMWH anti-Xa levels on 60 plasma samples with known AT activity from 12 enoxaparin-treated ALL/L patients, using four commercial kits from Siemens and Stago containing AT or not, on Siemens BCS and Stago STA R Max, respectively. Results: Of 236/240 samples with interpretable results, mean AT activity was 80% (46-138%). Correlation was acceptable for published kit ranges of LMWH anti-Xa levels when comparing kits containing AT (r = 0.82, P <.0001), or not (r = 0.93, P <.0001), and within a manufacturer (Berichrom to Innovance, r = 0.92, P <.0001; Stachrom to STA-Liquid Anti-Xa r = 0.98, P <.0001). LMWH anti-Xa levels were lower in platforms without added AT (P <.0001). For Stago kits, this effect increased when AT < 70% (P =.001, n = 19, mean 56%). Assay variability, measured as mean percent difference, was less pronounced with Stago kits (14.7%, n = 49) than Siemens (41.9%, n = 50). Conclusions: Although LMWH levels from anti-Xa assays with added AT trend higher than in those without, correlation was fairly good between platforms in pediatric ALL/L plasmas, even when AT activity was <70%.