A Novel Laboratory Assay to Monitor Unfractionated Heparin Dosing in Patients Taking Apixaban Prior to Hospital Admission

Abstract

Introduction When monitoring heparin, anti-Xa assays are susceptible to interference from apixaban taken before admission and can result in inappropriate dose adjustments that can negatively affect patient care. Methods We derived a novel assay, termed corrected heparin (CH), using quantified values from a chromogenic anti-Xa assay with heparin calibrators before and after heparinase treatment to eliminate any interference from apixaban within the patient sample. We retrospectively assessed 469 specimens from 72 patients at our institution who had their unfractionated heparin infusion monitored using the CH assay because of known apixaban use. These patients were included in the study if they had detectable apixaban levels (>0.1 IU/mL by anti-Xa). Results The analytical performance of the assay was evaluated, and precision was found to be 8.8% within 1 day and 13.3% over multiple days, with acceptable linearity (R2 = 0.997). Evaluation of clinical performance was compared with the partial thromboplastin time (PTT), showing a lack of correlation similar to comparisons between the PTT and anti-Xa assay (Blood Coagul Fibrinolysis 1993;4:635–8). The mean time to a therapeutic result in this cohort was 10 hours and 10 minutes. The CH assay was used to determine how long the apixaban was detected by the anti-Xa assay. The majority of patients (80%) still had measurable anti-Xa assay interference from apixaban at 24 hours after the last apixaban dose. Conclusions We have developed and evaluated an assay capable of quantifying heparin in the presence of apixaban. This assay showed acceptable performance in both analytical and clinical performance.

Comparison of Managing Factor Xa Inhibitor to Unfractionated Heparin Transitions by aPTT Versus a Treatment Guideline Utilizing Heparin Anti-Xa Levels

“…Finally, as our method relies primarily on commercially available UFH anti-Xa kits, it avoids burdening the lab from validating complex correction procedures. 13 As mentioned in the study methods, we had published our initial experiences of using UFH anti-Xa levels to guide FXai to UFH transitions. 12 We were concerned about possible residual anticoagulant effects of the FXai that could increase bleeding complications without providing likely therapeutic benefit, particularly for patients with delayed clearance of FXai such as acute kidney injury.…”

“…Finally, as our method relies primarily on commercially available UFH anti-Xa kits, it avoids burdening the lab from validating complex correction procedures. 13…”

“…The anti-Xa facility did not use any novel mechanism to “correct” the UFH anti-Xa assay, such as the use of heparinase. 13…”

“…The anti-Xa facility did not use any novel mechanism to "correct" the UFH anti-Xa assay, such as the use of heparinase. 13 Differences in UFH dosing standards vary slightly between the 2 institutions. At the aPTT center, the same standardized UFH starting dose is utilized for all patients with a 70 unit/kg loading dose (maximum of 7500 units) and a starting dose of 15 units/kg/h, with a soft maximum of 1500 units/h (nurse to contact provider if calculated dose is over 1500 units/h).…”

Monitoring of Anticoagulant Activity of Dabigatran and Rivaroxaban in the Presence of Heparins

“…Contamination with heparins may occur in patients requiring CVC connection; for example, those with renal failure, cancer, or malnutrition [5,6]. Although concomitant administration of heparin and DOAC is rare in clinical practice, in some situations (e.g., patients on DOAC treatment who receive LMWH before/after surgery or during hemodialysis), LMWHs may remain in the blood and disturb the precise measurement of DOACs' activity [4,[7][8][9][10].…”