Evaluation of Anti-Xa Apixaban and Rivaroxaban Levels With Respect to Known Doses in Relation to Major Bleeding Events.

BACKGROUND: Although not routinely recommended, anti-Xa level monitoring for apixaban or rivaroxaban may be useful in certain clinical scenarios. There are currently no laboratory standards, therapeutic ranges, or proven correlation between anti-Xa levels and clinical outcomes. OBJECTIVE: This study describes the utilization, application, and association of anti-Xa levels with clinical outcomes in patients receiving apixaban or rivaroxaban. METHODS: This retrospective, descriptive study included adult inpatients within the Houston Methodist System on apixaban or rivaroxaban with at least one anti-Xa level ordered subsequent to administered doses. The primary endpoint was major bleeding according to International Society on Thrombosis and Haemostasis criteria. Secondary endpoints included reasons for anti-Xa level ordering, anti-Xa levels at different time intervals post-dose, and thrombotic events. Pre-specified subgroup analyses were performed to further evaluate the primary endpoint. RESULTS: The study population consisted of 169 patients and 234 anti-Xa levels. Twenty-nine levels were obtained in context of major bleeding. The majority of levels were not drawn as peak levels 2-4 hours post-dose, however remained quantifiable above typical observed levels within this timeframe and well beyond 24 hours post-dose. Patient characteristics with major bleeding included elderly age, acute renal impairment, and low body weight. At least 14 unique reasons for anti-Xa level ordering were identified. Twenty-nine levels were associated with thrombotic events. CONCLUSION: Anti-Xa levels may be useful for assessment of current drug concentrations, immediate safety of therapy, and guidance for possible clinical interventions. Dose titration and reversal therapies based on anti-Xa level results in major bleeding warrant further research.

Apixaban and Rivaroxaban Anti-Xa Level Monitoring Versus Standard Monitoring in Hospitalized Patients With Acute Kidney Injury.

BACKGROUND: Oral direct factor Xa inhibitors (FxaIs) are renally eliminated; thus, acute kidney injury (AKI) may increase the risk for drug accumulation and bleeding. There is minimal data describing the effects of AKI on FxaI anti-Xa levels or clinical outcomes. OBJECTIVE: To compare anti-Xa level monitoring with standard monitoring in patients who experience AKI on apixaban or rivaroxaban. METHODS: This retrospective study included patients admitted within a large hospital system from May 2016 to October 2020. Patients were included if they received apixaban or rivaroxaban prior to AKI. Patients were stratified into 1 of 2 groups: those with anti-Xa level monitoring or those who received standard monitoring. The primary outcome was major bleeding as defined by the International Society of Thrombosis and Haemostasis. RESULTS: A total of 196 patients were included in the final analysis. Major bleeding occurred in 2 patients who received anti-Xa level monitoring, compared with 14 patients who received standard monitoring (2.1% vs 14%; P < 0.01). Variables identified as predictors of major bleeding included a documented history of liver disease (adjusted odds ratio = 3.17; 95% CI = 1.04-9.67; P = 0.04) and antiplatelet use (adjusted odds ratio = 4.18; 95% CI = 1.28-13.7; P = 0.02). CONCLUSION AND RELEVANCE: This is the first study to demonstrate that anti-Xa level monitoring was associated with a significant reduction in major bleeding compared with standard monitoring in patients with AKI who received apixaban or rivaroxaban. The optimal management of antithrombotic medications in patients with AKI and recent exposure to an FxaI requires further investigation.

Evaluation of characteristics and dosing regimens in patients with new or recurrent thrombosis on apixaban and rivaroxaban.

Direct factor Xa inhibitors, such as apixaban and rivaroxaban, are widely used for treatment and prevention of venous thromboembolism; however, recent cases of therapeutic failure have been reported. Potential risk factors associated with therapeutic failure such as dose deviations outside of package labeling recommendations, and the use of direct factor Xa-specific inhibitor levels to guide clinical decision making continue to be areas of further investigation. Our study aimed to describe characteristics and dosing regimens in patients on apixaban or rivaroxaban who experienced a new or recurrent thrombosis. We performed a retrospective chart review on 190 patients on either apixaban or rivaroxaban presenting to our institution with new or breakthrough thromboembolism. Evaluation of prescribed anticoagulation regimens compared to package labeling recommendations, direct factor Xa inhibitor-specific anti-Xa levels, anticoagulation interruptions, use of parenteral bridge anticoagulation, final anticoagulation regimen disposition, and thrombosis-associated mortality were recorded. In patients presenting with breakthrough thromboembolism, 78% were on a regimen that matched package labeling recommendations. Anti-Xa levels were documented in 66 patients, the majority of which fell within institutional expected ranges at time of thrombosis. Therapy interruptions immediately prior to thrombosis were observed in 22% of patients and 21% of those patients received parenteral anticoagulation during interruption. Upon discharge, 46% of patients continued the same anticoagulation regimen with no changes. The mortality rate was 6%. In patients who present with new thromboembolism on apixaban or rivaroxaban, a thorough review of risks and benefits should be conducted to mitigate future risk of recurrent thrombosis.

Patients with cirrhosis show a relative increase in thrombin generation that is correlated with lower antithrombin levels.

Predicting the risk of bleeding or thrombosis in cirrhotic patients is difficult due to reduced levels and dysregulation of both procoagulant and anticoagulant factors. We utilized thrombin generation and microvesicle analysis to better understand the regulation of haemostasis in cirrhotic patients. We studied 24 patients with cirrhosis vs. 21 healthy controls. Cirrhotic patients had reduced prothrombin activity (40 ±â€Š9 vs. 112 ±â€Š15), protein C activity (36 ±â€Š10 vs. 114 ±â€Š19) and antithrombin activity (43 ±â€Š14 vs. 109 ±â€Š10). Peak thrombin generation was reduced in cirrhotic patients (165 ±â€Š47 vs. 232 ±â€Š101), but the ratio of peak thrombin generation to prothrombin activity was increased in cirrhotic patients (4.2 ±â€Š1.0 vs. 2.1 ±â€Š0.9) indicating a relative increase in thrombin generation in cirrhosis. The termination time ratio was increased in cirrhotic patients (7.2 ±â€Š1.9 vs. 3.1 ±â€Š0.7) and correlated with reduced antithrombin levels, indicating that cirrhotic patients took longer to stop thrombin generation than controls. Cirrhotic patients showed reduced procoagulant microvesicles from platelets (39 500 ±â€Š24 800 vs. 107 700 ±â€Š74 200) and other cells, but levels overlapped with controls. Cirrhotic patients showed a wide range of procoagulant and anticoagulant levels leading to variability in the regulation of thrombin generation. In conclusion, compared with healthy controls, patients with cirrhosis have lower antithrombin levels that lead to slower downregulation of thrombin generation and more overall thrombin being produced for a given procoagulant level in blood, but also low normal levels of procoagulant microvesicles that would slow initiation of thrombin generation. Whether an individual cirrhosis patient is at a greater risk of bleeding vs. thrombosis may depend on their specific imbalance in procoagulants vs. anticoagulants.