American Society for Clinical Pathology and American Society for Clinical Laboratory Science
View all recommendations from this societyNovember 7, 2022
Don’t employ a specific direct oral anticoagulant [DOAC] reversal agent without identifying the DOAC and estimating its plasma concentration.
In 2015, the US FDA approved idarucizumab as a reversal immunoglobulin specific for the direct thrombin inhibitor dabigatran. In 2018, andexanet alfa was approved as a factor Xa mimetic reversal agent for the direct anti-Xa oral anticoagulants rivaroxaban and apixaban. Clinicians employ reversal agents to control major bleeding associated with presumed DOAC overdose when compression, blood product support, and antifibrinolytics are ineffective, often in preparation for an invasive procedure. A reversal agent should be employed only when the clinician can identify the DOAC using, for instance, an anti-Xa assay* or dilute thrombin time [DTT] assay*, establish the likelihood that it is the bleeding source, and estimate its dose or plasma concentration. In addition to their documented risk of ischemic complications, reversal agents are maintained in collaborative inventory systems with controlled access, owing to scarcity and costs. Andexanet alfa, for instance, costs $27,500 for a low dose regimen and $49,500 for a high dose, and CMS reimbursement is limited to 50% of the low dose investment. A rapid urinary “dipstick” detection device* is a viable point-of-care alternative to the anti-Xa or DTT assays as the stick distinguishes dabigatran from the anti-Xa inhibitors.6 For those facilities that do not offer a rapid turnaround DOAC assay specific to the agent, clinicians must establish the DOAC identity and time of the most recent dosage by history before establishing treatment. Healthcare systems shall collaborate with the laboratory medicine service to develop strategies that ensure efficacy and stewardship of reversal agents.8 *Off-label or research use only.
These items are provided solely for informational purposes and are not intended as a substitute for consultation with a medical professional. Patients with any specific questions about the items
on this list or their individual situation should consult their physician.
How The List Was Created
(1–4) The American Society for Clinical Pathology (ASCP) list of recommendations was developed under the leadership of the ASCP Effective Test Utilization Steering Committee. This committee is chaired by an ASCP Past President and is comprised of subject matter and test utilization experts across the fields of pathology and laboratory medicine. The committee considered a list of possible recommendations compiled as the result of a survey administered to Society members serving on ASCP’s many commissions, committees and councils. In addition, an announcement was made to ASCP’s Advisory Board seeking suggestions for possible recommendations to promote member involvement. The laboratory tests targeted in our recommendations were selected because they are tests that are performed frequently; there is evidence that the test either offers no benefit or is harmful; use of the test is costly and it does not provide higher quality care; and eliminating it or changing to another test is within the control of the clinician. Implementation of these recommendations will result in higher quality care, lower costs and a more effective use of our laboratory resources and personnel.
(5) This recommendation was developed under the leadership of ASCLS’s Choosing Wisely Committee and the ASCLS Board of Directors. The Committee examined numerous options based on evidence available. Subject matter experts from the ASCLS Scientific Assemblies reviewed, edited, and recommended approval of this recommendation, which was subsequently reviewed and approved by the ASCLS Board of Directors.
Sources
Milling TJ, Pollack CV. A review of guidelines on anticoagulation reversal across different clinical scenarios—is there a general consensus? Am J Emergency Med2020; 38: 1890–1903.
Donnolly SJ, Crowther M, Eikelboom JW, et al. Full study report of andexanet alfa for bleeding associated with factor Xa inhibitors. NEJM 2019; 380: 1326–35.
Sobolewski KA, Brophy A, Choi S, Opsha Y. Real-world observational review of andexanet alfa prescribing and utilization outcomes at a community teaching hospital. Crit Care Explorations. 2021; 3: e0356. Published online 2021 Apr 2. doi: 10.1097/CCE.0000000000000356.
Nederpelt CJ, Naar L, Sylvester KQ, et al. Evaluation of oral factor Xa inhibitor-associated extracranial bleeding reversal with andexanet alfa. J Thromb Haemost. 2020;18:2532–41.
Cuker A, Burnett A, Triller D, et al. Reversal of direct oral anticoagulants. Guidance from the Anticoagulation Forum. Am J Hematol 2019; 94: 697–709.
Harenberg J, Du S, Wehling M, et al. Measurement of dabigatran, rivaroxaban and apixaban in samples of plasma, serum and urine, under real life conditions. An international study. Clin Chem Lab Med 2016; 54: 275–83.
Bhatt SH. Implementing effective protocols when using direct oral anticoagulant reversal agents: a review of updated guidelines and clinical data. Pharmacy Time Continuing Education 2020: 68–85.
Nederpelt CJ, Naar L, Sylvester KW, et al. Evaluation of oral factor Xa inhibitor-association extracranial bleeding reversal with andexanet alfa. J Thromb Haemost 2020: 18: 2532–41.
