title: Clinical applicability of the anti Xa assay to monitor unfractionated heparin in non-cardiac arterial procedures: a scoping review
Creators: name: Hoebink, Max
name: Smit, Sjoerd
name: Steunenberg, Thomas
name: Hamer, Henrike
name: Wiersema, Arno M.
name: Jongkind, Vincent
name: Kak Khee Yeung
Publisher: name: OSF Registries
Year: 2023
Subjects: subject: Surgical Procedures, Operative
subject: Diseases
subject: Medicine and Health Sciences
subject: Cardiovascular Diseases
subject: Analytical, Diagnostic and Therapeutic Techniques and Equipment
subject: Other Analytical, Diagnostic and Therapeutic Techniques and Equipment

description: Unfractionated heparin (UFH) is being used to reduce thrombo-embolic complications (TEC) non-cardiac arterial procedures (NCAP) and cardiac surgery for over 70 years. Heparin decreases coagulation and the heparin effect in the individual patient is unpredictable, leading to an increased risk of bleeding complications during surgery. Differences in heparin efficacy have been described between different brands and also batches of the same brand. An adequate balance between TEC reduction without an increase in bleeding complications has to be found. Monitoring the heparin effect to prevent TEC and bleeding complications is an increasingly used concept in NCAP and already established in cardiac surgery. A variety of heparin essays is being used: i.e. activated partial thromboplastin time, thrombin time, plasma heparin concentration). During NCAP and also cardiac surgery, Activated Clotting Time (ACT) is the predominantly used monitoring essay, as ACT is a reliable point of care test, which can be performed within limited time. However, evidence on ACT guided heparinization during NCAP is still scarce and ACT also has disadvantages. Measurement results are affected by hypothermia, hemodilution, medication, platelet count, factor deficiencies and several diseases. Additionally, different ACT measurement devices are being used in clinical practice. These devices vary in clot detection techniques (detecting a decreased rate of a gravity dependent descent of a plunger system or a metal chip detected by a magnetic sensor) or contact activator reagents (i.e. kaolin or celite). Variations in measurements until 68 seconds have been described between different devices when analysing simultaneously taken blood samples. Results between different devices are therefore not interchangeable and ACT lacks standardization. Heparin is also measured by the anti Xa assay, which provides a measure of functional heparin level in plasma. To measure anti Xa, a known excess quantity of Xa antibodies is added to a plasma monster. Heparin-antithrombin-Xa (anti Xa) complexes are formed and anti Xa activity is measured by detecting residual Xa antibodies with a chromogenic substrate, or using a clotting based assay. Together with the protamine titration assay, the anti Xa assay is regarded as the standard to determine the appropriate APTT range level in clinical laboratories. Anti Xa is a frequently applied assay in the non-operative setting to monitor UFH when other monitoring modalities pose disadvantages (i.e. COVID-19, neonates, lupus anticoagulant, coagulant factor deficiencies). Also, application of Anti Xa measurements to monitor heparin anticoagulation is described extensively for venous thromboembolism and during extracorporeal membrane oxygenation (EMCO) or cardiopulmonary bypass interventions. Processing Anti Xa measurements is taking substantial time and ACT therefore seems a more suitable assay during surgery, but ACT measurement methods could potentially be validated for NCAP based on anti Xa. Given the known disadvantages of ACT, anti Xa could be an asset during specific patients or during specific NCAP. However, evidence on clinical applicability of anti Xa in NCAP is scarce and clinical applicability is currently unclear. Therefore, the aim of this systematic review, designed as a scoping review, is to structure the existing body of evidence regarding the use of the anti Xa measurements to monitor UFH in arterial procedures to determine its clinical applicability in NCAP. Cardiac surgical procedures as well as NCAP will be incorporated in this review.