Optimization of Heparin Monitoring with Anti-FXa Assays and Impact of Dextran Sulfate for Measuring All In-Vivo Drug Activity

Heparins, Unfractionated or Low Molecular Weight, are permanently at the spotlight of both clinical indications and laboratory monitoring. An accurate drug dosage is necessary for an effi-cient and safe therapy. The one-stage anti-FXa kinetics’ assays are the most widely and universally used with full automation for large series, without needing exogenous Antithrombin. WHO in-ternational standards are available for UFH and LMWH, but external quality assessment surveys still report a high inter-assay variability. This heterogeneity results from: assay formulation, designed without or with dextran sulfate to measure all heparin in blood circulation; calibrators for testing UFH or LMWH with the same curve; and automation parameters. The various factors which impact heparin measurements are reviewed, and we share our experience to optimize assays for completely testing plasma heparin. Evidence is provided on the usefulness of low molecular weight dextran sulfate to mobilize all drug present in blood circulation. Other key factors concern adjustment of assay conditions to obtain fully superimposable calibration curves for UFH and LMWH, and automation parameters. The study is illustrated by the performances of the various anti-FXa assays used for testing heparin on UFH or LMWH treated patients’ plasmas and obtained using citrate or CTAD anticoagulants. Comparable results are obtained only when CTAD anti-coagulant is used. Using citrate UFH is underestimated in the absence of dextran sulfate. Heparin calibrators, adjustment of automation parameters and data treatment contribute to other smaller differences.

Discordance between aPTT and anti-factor Xa levels and implications in patients receiving intravenous unfractionated heparin therapy

Heparin, one of the world’s oldest anticoagulation medications, accelerates the rate ofinhibition of previously activated clotting factors. It is most often used in the prophylaxis andtreatment of thromboembolic disorders and complications associated with atrial fibrillation.The two most common ways to monitor plasma heparin levels and anticoagulation therapyare the activated partial thromboplastin time (aPTT) and anti-factor Xa assay (anti-Xa). Thisarticle assesses the performance of aPTT and anti-Xa monitoring protocols and analyzes thediscordance between aPTT and anti-Xa levels and its clinical implications in patients receivingintravenous heparin therapy.