Clinical Anticoagulant Measurement

Haemostasis reflects a balance between procoagulant and anticoagulant forces. A relative excess of procoagulant forces and/or a relative lack of anticoagulant forces can predispose individuals to an increased risk of thrombosis. Conversely, a relative lack of procoagulant forces and/or a relative excess of anticoagulant forces can predispose individuals to an increased risk of bleeding. It is possible in several clinical situations to mitigate bleeding risk using various approaches, including provision of procoagulant material; conversely, thrombosis risk can be mitigated by using various clinical anticoagulants. In some cases, such therapies require laboratory monitoring or measurements; in particular, therapy using anticoagulants may require laboratory measurements or monitoring to ensure adequate anticoagulation without over- or under-coagulating patients, and thereby reducing any treatment-associated risk of bleeding or thrombosis. In this narrative review, we detail the various anticoagulants under current clinical use, as well as the tests or assays used to measure anticoagulant levels or to monitor anticoagulant therapy.

Favaloro EJ, Arunachalam S, Pasalic L. External quality assessment for unfractionated heparin monitoring: an update from Australasia/Asia-Pacific. Semin Thromb Hemost. 2026;52(8):956–66. doi: 10.1055/a-2779-0035. PMID: 41443250.

Abstract

Unfractionated heparin (UFH) remains a major anticoagulant therapy applied within the acute hospital system. Due to intra- and interpatient variability, UFH monitoring needs to be applied to ensure patients remain free of thrombotic and bleeding complications at too low and too high an UFH level, respectively. Monitoring of UFH therapy is usually achieved using either an activated partial thromboplastin time (aPTT) or an anti-factor Xa (anti-Xa) method. The former is a clotting assay that evaluates both the anti-factor IIa (anti-IIa or anti-thrombin) and anti-Xa anticoagulant activity of UFH and the latter is a chromogenic assay that evaluates just the anti-Xa anticoagulant activity of UFH. The aPTT method is perhaps more widely utilized since aPTT testing is performed by all hemostasis laboratories performing routine coagulation tests. However, the aPTT method requires establishment of an aPTT UFH therapeutic range. The anti-Xa method is favored in larger hospital sites and by most experts and uses a standard UFH therapeutic range. We report findings for aPTT and anti-Xa testing for UFH monitoring in our geographic region using recent data (testing for the past 5 years; 2020–2024 inclusive) from the Royal College of Pathologists of Australasia Quality Assurance Program, an international external quality assessment (EQA) program, with over 110 enrolments for this EQA module. Four samples are assessed each year, with these comprising various levels of UFH. Good reproducibility was observed for duplicate samples sent in different surveys. Coefficient of variation (%) data revealed moderate variation for samples containing UFH (10–40% for anti-Xa; 10–25% for aPTT). Anti-Xa reagents containing dextran sulphate tended to yield higher anti-Xa values than those without. Interpretations regarding UFH levels being below, within, or above therapeutic levels were generally reported as expected, according to the level of UFH present in the sample, especially for anti-Xa testing.

Favaloro EJ, Arunachalam S, Pasalic L. External quality assessment for low molecular weight heparin monitoring in the Australasia/Asia-Pacific Region. Semin Thromb Hemost. 2026;52(8):967–74. doi: 10.1055/a-2900-7026. PMID: 42398957. 

Abstract

Low molecular weight heparin (LMWH) remains a widely utilized parenteral anticoagulant in hospital and outpatient settings for thromboprophylaxis and treatment of venous thromboembolism. While LMWH typically does not require routine monitoring due to predictable pharmacokinetics, anti-factor Xa (anti-Xa) monitoring is indicated in specific populations, including those with renal impairment, extremes of body weight, pregnancy, or unexplained treatment failure. LMWH monitoring relies exclusively on chromogenic anti-Xa assays, as LMWH‘s predominant anti-Xa activity with minimal anti-IIa effect renders activated partial thromboplastin time insensitive. Therapeutic targets are context-dependent: peak anti-Xa levels of 0.5 to 1.2 U/mL for twice-daily therapeutic dosing or 1.0 to 2.0 U/mL for once-daily dosing, measured 3- to 5-hour postdose. We report external quality assessment findings for anti-Xa testing of LMWH from the past 6 years (2020–2025 inclusive) using RCPAQAP (Royal College of Pathologists of Australasia Quality Assurance Program) data, an international program with approximately 150 laboratory enrolments. Four samples are assessed annually at varied LMWH concentrations (0, 0.2–0.3, 0.5–0.6, 0.8–1.0 U/mL). Good reproducibility was demonstrated for duplicate samples across surveys. Coefficient of variation data revealed moderate variability (10–25%) for detectable LMWH levels, lower than unfractionated heparin (UFH) monitoring variability. Method-related differences were observed, with Siemens Innovance anti-Xa assays yielding slightly higher values than Werfen HemosIL or Stago STA assays. Participant interpretations of LMWH levels (below/within/above therapeutic range) showed greater variability than UFH due to multiple valid therapeutic ranges for LMWH depending on dosing context. Overall, laboratories demonstrated acceptable analytical and interpretative performance for LMWH monitoring, which should provide some reassurance to both patients and their clinical carers.