Assessment of Temporary Warfarin Reversal in Patients With Left Ventricular Assist Devices: the KVAD Study.

BACKGROUND: Patients with left ventricular assist devices (LVADs) require interruption of warfarin for invasive procedures, but parenteral bridging is associated with many complications. Four-factor prothrombin complex concentrate (4F-PCC) can temporarily restore hemostasis in patients undergoing anticoagulation with warfarin. OBJECTIVES: This pilot study evaluated the strategy of using variable-dose 4F-PCC to immediately and temporarily reverse warfarin before invasive procedures without holding warfarin in patients with LVADs. The duration of effect of 4F-PCC on factor levels and time to reestablish therapeutic anticoagulation post procedure were assessed. METHODS: Adult patients with LVADs and planned invasive procedures were enrolled from a single center. Warfarin was continued uninterrupted. The 4F-PCC dose administered immediately pre-procedure was based on study protocol. International normalized ratio (INR)- and vitamin K-dependent factor levels were collected before and during the 48 hours after 4F-PCC administration. The use of parenteral bridging, International Society for Thrombosis and Haemostasis major and clinically relevant nonmajor bleeding (CRNMB) and thromboembolic events at 7 and 30 days were collected. RESULTS: In 21 episodes of 4F-PCC reversal, median baseline INR was 2.7 (IQR 2.2-3.2). The median dosage of 4F-PCC administered was 1794 units (IQR 1536-2130). At 24 and 48 hours post 4F-PCC administration, median INRs were 1.8 (IQR 1.7-2.0) and 2.0 (IQR 1.9-2.4). Two patients required postoperative bridging. One patient experienced major bleeding within 72 hours, and 2 experienced CRNMB within 30 days. There were no thromboembolic events. Baseline and post 4F-PCC vitamin K-dependent factor levels corresponded with changes in INR values. The median time to achieve therapeutic INR post-procedure was 2.5 days (IQR, 1-4). CONCLUSION: Administration of 4F-PCC for temporary reversal of warfarin for invasive procedures in patients with LVADs allowed for continued warfarin dosing with minimal use of post-intervention bridging, limited bleeding and no thromboembolic events.

Multicenter evaluation of left ventricular assist device implantation with or without ECMO bridge in cardiogenic shock.

BACKGROUND: The efficacy of extracorporeal membrane oxygenation (ECMO) as a bridge to left ventricular assist device (LVAD) remains unclear, and recipients of the more contemporary HeartMate 3 (HM3) LVAD are not well represented in previous studies. We therefore undertook a multicenter, retrospective study of this population. METHODS AND RESULTS: INTERMACS 1 LVAD recipients from five U.S. centers were included. In-hospital and one-year outcomes were recorded. The primary outcome was the overall mortality hazard comparing ECMO versus non-ECMO patients by propensity-weighted survival analysis. Secondary outcomes included survival by LVAD type, as well as postoperative and one-year outcomes. One hundred and twenty-seven patients were included; 24 received ECMO as a bridge to LVAD. Mortality was higher in patients bridged with ECMO in the primary analysis (HR 3.22 [95%CI 1.06-9.77], p = 0.039). Right ventricular assist device was more common in the ECMO group (ECMO: 54.2% vs non-ECMO: 11.7%, p < 0.001). Ischemic stroke was higher at one year in the ECMO group (ECMO: 25.0% vs non-ECMO: 4.9%, p = 0.006). Among the study cohort, one-year mortality was lower in HM3 than in HeartMate II (HMII) or HeartWare HVAD (10.5% vs 46.9% vs 31.6%, respectively; p < 0.001) recipients. Pump thrombosis at one year was lower in HM3 than in HMII or HVAD (1.8% vs 16.1% vs 16.2%, respectively; p = 0.026) recipients. CONCLUSIONS: Higher mortality was observed with ECMO as a bridge to LVAD, likely due to higher acuity illness, yet acceptable one-year survival was seen compared with historical rates. The receipt of the HM3 was associated with improved survival compared with older generation devices.

Activated Clotting Times Demonstrate Weak Correlation With Heparin Dosing in Adult Extracorporeal Membrane Oxygenation.

BACKGROUND: The optimal monitoring strategy for anticoagulation management in extracorporeal membrane oxygenation (ECMO) remains a clinical controversy. The Extracorporeal Life Support Organization Anticoagulation Guidelines suggest that multiple anticoagulation assays may be needed but do not specify a preferred management strategy. STUDY QUESTION: In adult ECMO patients, which anticoagulation assays demonstrate the highest correlation with unfractionated heparin (UFH) dose requirements? STUDY DESIGN: We performed a retrospective chart review of adult patients cannulated to ECMO between February 2013 and July 2015. MEASURES AND OUTCOMES: The primary outcome was the correlation between activated clotting time (ACT), activated partial thromboplastin time (aPTT), and anti-Xa and UFH dose. Secondary outcomes included correlations between anticoagulation assays. Correlations were calculated for the entire cohort, with subgroup analysis of venoarterial and venovenous ECMO patients. RESULTS: Forty-eight patients were included in the analysis, 26 initially cannulated to venoarterial ECMO and 22 to veno-venous ECMO. The median duration of ECMO therapy was 7 days. Mean UFH requirements were 1149 units/h or 15.3 units/kg/h. Total UFH dose was most correlated with anti-Xa levels (r = 0.467), whereas weight-based heparin dose was most correlated with aPTT (0.405). For correlations between anticoagulation assays, anti-Xa and aPTT were more highly correlated with each other (r = 0.633) compared with ACT. CONCLUSIONS: In adult patients requiring ECMO, anti-Xa and aPTT monitoring were correlated more closely with UFH dosing than ACT.

Evaluation of the use of direct oral anticoagulants for the management of heparin-induced thrombocytopenia.

Historically, treatment of heparin-induced thrombocytopenia (HIT) includes a non-heparin parenteral anticoagulant with bridging to warfarin once platelets recover. Data supporting the use of direct oral anticoagulants (DOACs) for HIT treatment are limited. Given the paucity of evidence for the use of DOACs in HIT, the aim of this study is to describe the prescribing patterns of DOACs for HIT at our institution. This is a single center, retrospective chart evaluation of patients admitted from January 2017 to October 2020 with a confirmed diagnosis of HIT. Twenty-six patients were identified; 21 patients (81%) received initial parenteral treatment and 5 patients (19.2%) with initial DOAC treatment. The most frequently used DOAC was apixaban at the VTE treatment dose [15 (57.7%)] followed by the reduced dose of apixaban [5 (19.2%)]. Of the patients initially treated with a parenteral agent, 11 (42.3%) were transitioned to a DOAC after platelet recovery, 7 (26.9%) transitioned as platelets were steadily increasing, and 3 (11.5%) transitioned at the time of discharge (prior to platelet recovery). Platelet recovery was achieved in 23 patients (88.5%) at a median of 5 days (IQR 2.8-8.3) after HIT diagnosis. No new thrombotic or bleeding events occurred within 30 days of HIT diagnosis. In our patients treated with a DOAC for HIT, no progression of HIT was observed. Apixaban was the most frequently utilized DOAC. Most patients received a parenteral anticoagulant prior to DOAC initiation. All patients managed with a DOAC as initial treatment achieved platelet recovery within 30 days of HIT diagnosis.

Extended duration venous thromboembolism prophylaxis with betrixaban for patients re-admitted with venous thromboembolism.

Patients hospitalized for an acute medical illness remain at risk of developing venous thromboembolism (VTE) post-discharge. Betrixaban, an oral direct Factor Xa inhibitor, is approved for extended VTE thromboprophylaxis in acutely ill medical patients. The primary objective of this study was to evaluate patients re-admitted with VTE within 30 days of discharge to determine if they would have been eligible for extended duration VTE prophylaxis during the index admission. We used three different sets of eligibility criteria: the APEX study criteria, the Bevyxxa® (betrixaban) package insert, and Mass General Brigham HealthCare System's Center for Drug Policy Guidelines. A secondary aim was to describe the reasons for ineligibility. Within 30 days of the index hospital admission, 226 patients were re-admitted with new VTE between January 2017 and December 2018. Of these, 134 (59%) were excluded based on pre-defined exclusion criteria. Of the remaining 92, 22 patients (23.9%) were eligible based on the APEX study criteria, 26 patients (28.2%) based on Mass General Brigham HealthCare System's Center for Drug Policy Guidelines, and 92 patients (100%) based on the Bevyxxa® package insert. There were 22 patients (23.9%) who were eligible for VTE prophylaxis with betrixaban based on all three criteria. Appropriate betrixaban use may have prevented some of the VTE events and re-admissions that occurred within 30 days of initial hospital discharge.

Evaluation and optimization of prescribed concomitant antiplatelet and anticoagulation therapy centrally managed by an anticoagulation management service.

Patients on long-term anticoagulation combined with antiplatelet therapy have an increased risk of bleeding compared to patients on anticoagulation alone. The aim of this study was to evaluate the appropriateness of antiplatelet therapy in patients who are on long-term warfarin therapy and are managed by Brigham and Women's Hospital Anticoagulation Management Service (BWH AMS). This was a single-center, prospective chart review of patients managed by BWH AMS who were on long-term warfarin therapy plus full-dose aspirin (325 mg), an oral P2Y12 inhibitor (clopidogrel, prasugrel or ticagrelor) and/or acetylsalicylic acid/dipyridamole. Patients' cardiovascular (CV) benefit and risk of bleeding were assessed according to clinical guidelines. The major objective of the study was to determine the proportion of patients on dual antithrombotic therapy (DAT) or triple antithrombotic therapy (TAT) whose risk of bleeding outweighed CV benefit. Of the 2677 patients evaluated for inclusion,145 were on concomitant long-term warfarin therapy plus aspirin (325 mg), an oral P2Y12 inhibitor and/or acetylsalicylic acid/dipyridamole. A total of 85 patients (58.6%) had no clear indication for DAT or TAT per guideline recommendations and were categorized as bleeding risk outweighing CV benefit. The remaining 60 patients (41.4%) had an appropriate indication for DAT or TAT per guidelines and were categorized as CV benefit outweighing bleeding risk. BWH AMS pharmacists made 33 (22.9%) recommendations to providers to discontinue or de-escalate antiplatelet therapy. Interventions were accepted for 10 (30.3%) patients. Pharmacist involvement in the management of patients' antithrombotic regimens can optimize guideline-directed medical therapy and mitigate the potential risk of bleeding.

Cerebrovascular Accidents During Mechanical Circulatory Support: New Predictors of Ischemic and Hemorrhagic Strokes and Outcome.

BACKGROUND AND PURPOSE: Left ventricular assist devices (LVADs) have emerged as an effective treatment for patients with advanced heart failure refractory to medical therapy. Post-LVAD strokes are an important cause of morbidity and reduced quality of life. Data on risks that distinguish between ischemic and hemorrhagic post-LVAD strokes are limited. The aim of this study was to determine the incidence of post-LVAD ischemic and hemorrhagic strokes, their association with stroke risk factors, and their effect on mortality. METHODS: Data are collected prospectively on all patients with LVADs implanted at Brigham and Women's Hospital. We added retrospectively collected clinical data for these analyses. RESULTS: From 2007 to 2016, 183 patients (median age, 57; 80% male) underwent implantation of HeartMate II LVAD as a bridge to transplant (52%), destination therapy (39%), or bridge to transplant candidacy (8%). A total of 48 strokes occurred in 39 patients (21%): 28 acute ischemic strokes in 24 patients (13%) and 20 intracerebral hemorrhages in 19 patients (10.3%). First events occurred at a median of 238 days from implantation (interquartile range, 93-515) among those who developed post-LVAD stroke. All but 9 patients (4.9%) were on warfarin (goal international normalized ratio, 2-3.5) and all received aspirin (81-325 mg). Patients with chronic obstructive pulmonary disease were more likely to have an ischemic stroke (odds ratio, 2.96; 95% confidence interval, 1.14-7.70). Dialysis-dependent patients showed a trend toward a higher risk of hemorrhagic stroke (odds ratio, 6.31; 95% confidence interval, 0.99-40.47). Hemorrhagic stroke was associated with higher mortality (odds ratio, 3.92; 95% confidence interval, 1.34-11.45) than ischemic stroke (odds ratio, 3.17; 95% confidence interval, 1.13-8.85). CONCLUSIONS: Stroke is a major cause of morbidity and mortality in patients on LVAD support. Chronic obstructive pulmonary disease increases the risk of ischemic stroke, whereas dialysis may increase the risk of hemorrhagic stroke. Although any stroke increases mortality, post-LVAD hemorrhagic stroke was associated with higher mortality compared with ischemic stroke.

Four factor prothrombin complex concentrate for warfarin reversal in patients with left ventricular assist devices.

Continuous flow left ventricular assist devices (CF-LVAD) require therapeutic anticoagulation which is often interrupted for procedures or bleeding. Prior to the availability of four factor prothrombin complex concentrate (4F-PCC) in the United States, warfarin was held and its effects reversed by vitamin K or fresh frozen plasma. We evaluated the use of 4F-PCC for temporary warfarin reversal in patients with CF-LVADs and assessed outcomes. This analysis is a retrospective study of CF-LVAD patients who received 4F-PCC for warfarin reversal in the setting of bleeding or need for urgent or elective procedures. Primary outcome assessments included feasibility of administration in elective versus emergent situations, safety measured as incidence of thrombotic events, and change in INR after administration. In total, 37 CF-LVAD patients received 49 4F-PCC administrations. The average 4F-PCC dose was 1842 units (range 518-4292 units), or 22 units/kg (range 5.8-58 units/kg). 4F-PCC significantly decreased the mean INR from 2.9 to 1.7 (p < 0.0001) in 47 of 49 administrations; two patients did not have post infusion INR testing. No cases of new confirmed or suspected pump thrombosis, stroke, venous thromboembolism, arterial thrombosis, or myocardial infarction were observed within 30 days of administration of 4F-PCC. 4F-PCC administration for temporary warfarin reversal was demonstrated to be feasible, effective, and, safe in CF-LVAD patients and judged to be 96% effective in patients for whom data were available. We observed no thrombotic events attributed to use of 4F-PCC.

Expanding anticoagulation management services to include direct oral anticoagulants.

Despite the ease of use of direct oral anticoagulants (DOACs), these agents remain high risk medications and their clinical efficacy can be impacted by factors such as patient adherence, drug procurement barriers, bleeding leading to discontinuation, and prescribing that deviates from approved dosing regimens. Clinical monitoring of patients on DOACs should be performed by clinicians who specialize in anticoagulation and are familiar with the nuances of DOAC dosing, monitoring, and other components of anticoagulation management including peri-procedural management and care transitions. Although data for centralized warfarin management have consistently demonstrated improved clinical outcomes compared to traditional management by individual community providers, there are no published data addressing the impact of centralized management of DOACs on clinical outcomes or anticoagulation control. In addition, there is currently no consensus on how to incorporate patients on DOACs into this centralized model, despite recommendations for systematic follow-up by both the Anticoagulation Forum and the Institute for Safe Medication Practices. Based on the national recommendations and an identified institutional need, the Brigham and Women's Hospital Anticoagulation Management Service implemented a pilot program to expand services to include patients newly initiated on, or transitioned to, a DOAC. We describe our model for expansion of the AMS to include patients on DOACs.

Prospective evaluation of a bivalirudin to warfarin transition nomogram.

Bivalirudin may cause a falsely prolonged international normalized ratio (INR) that complicates the discontinuation of bivalirudin when used as a bridge to warfarin. To prospectively validate our novel bivalirudin to warfarin transition nomogram, adult patients who received bivalirudin as a bridge to warfarin between July 2015 and June 2016 were prospectively evaluated, utilizing our predictive nomogram. The major outcome of our analysis was the correlation between the predicted change in INR upon bivalirudin discontinuation based on the nomogram, and the actual change in INR upon bivalirudin discontinuation. The major outcome was analyzed using the Pearson's correlation test. A Pearson's correlation coefficient >0.6 was considered to be a strong correlation. Bivalirudin was used as a bridge to warfarin in 29 patients. The majority of patients (86%) included in the analysis had a ventricular assist device. The median initial bivalirudin rate was 0.07 mg/kg/h and the mean increase in INR when starting bivalirudin was 0.6. The mean final weight-based bivalirudin rate was 0.08 mg/kg/h and the mean change in INR after stopping bivalirudin was 0.7. The Pearson correlation coefficient between the predicted change in INR upon bivalirudin discontinuation and the actual change in INR upon bivalirudin discontinuation was 0.86 (p < 0.001). After bivalirudin discontinuation, 68% of patients had a therapeutic INR. The results of this prospective analysis successfully validated our novel bivalirudin to warfarin transition nomogram. There was a very strong correlation between the predicted change and actual change in INR upon bivalirudin discontinuation.

Treatment of heparin-induced thrombocytopenia before and after the implementation of a hemostatic and antithrombotic stewardship program.

In October 2013, we implemented a hemostatic and antithrombotic (HAT) stewardship program with the primary focus of ensuring appropriate use of intravenous direct thrombin inhibitors (DTI) in patients with heparin-induced thrombocytopenia (HIT). We sought to compare the duration and cost of DTI therapy for the management of HIT before and after implementation of the HAT stewardship program. Following institutional review board approval, we conducted a single center, retrospective chart review of all patients with a suspected diagnosis of HIT as assessed by an anti-heparin-PF4 enzyme-linked immunosorbent assay 6 months pre-HAT and post-HAT implementation. Patients were excluded if they were initiated on a DTI at an outside hospital, had a prior episode of HIT, or received mechanical circulatory support. Clinical characteristics, including demographics, comorbidities, medications, laboratory values, clinical and safety outcomes, length of stay, and mortality, were collected. A total of 592 patients were included; 333 patients were evaluated pre-HAT, while 259 patients were evaluated post-HAT. The mean duration of DTI treatment was significantly decreased in the post-HAT cohort (6.64 vs 5.17 days, p = 0.01), primarily driven by decreased duration of use for patients with suspected HIT (4.07 vs 2.86 days, p = 0.01). The HAT Stewardship program demonstrated a total decrease in annual costs associated with the diagnosis and management of HIT of $248,500. Our results indicate that the implementation of the HAT stewardship program had a significant impact on reducing the duration and costs of DTI therapy and the costs of laboratory evaluations in the management of HIT at our institution.

Comparison of Time to Therapeutic aPTT in Patients Who Received Continuous Unfractionated Heparin After Implementation of Pharmacy-wide Intervention Alerts.

Background: For patients on continuous IV unfractionated heparin (UFH), failing to achieve a therapeutic aPTT by 24 hours can be associated with increased morbidity. A pharmacy clinical surveillance system (PCSS) subtherapeutic aPTT alert was implemented at our institution to improve achievement of therapeutic aPTT goals by 24 hours. Objective: The primary objective was the time to achieve the minimum goal aPTT before and after the alert implementation. The secondary objectives were to examine the percentage of patients who achieved the minimum goal aPTT by 24 hours and the number of dose changes to achieve the minimum goal aPTT. Methods: A single-center retrospective study was conducted to include all adult inpatients receiving a continuous UFH infusion during a 3-month period prior to the implementation of a subtherapeutic aPTT alert and a 3-month period after implementation. Results: 317 patients were included in the analysis. The average time to achieve the minimum goal aPTT was 21.8 hours prior to alert implementation and 15.4 hours after implementation (p = .002). The percent of patients who achieved the minimum goal aPTT by 24 hours was 65.7% prior to alert implementation and 82.4% after implementation (p = .035). The average number of dose changes necessary to achieve aPTT value to the minimum goal aPTT prior to alert implementation was 1.67 and 1. 98 after implementation (p = .68). Conclusion: This analysis showed that implementation of a PCSS subtherapeutic aPTT alert for patients on continuous UFH infusions may ensure patients reach goal aPTT faster and facilitate a higher percent of patients who achieve the minimum goal aPTT by 24 hours.

Pharmacy Response to the Boston Marathon Bombings at a Tertiary Academic Medical Center.

OBJECTIVE: Effective crisis response requires multidisciplinary communication and rapid action. Our goals are to highlight the experience of a pharmacy department's response to the 2013 Boston Marathon bombing, to discuss the role of the pharmacist in a crisis response, and to identify potential learning opportunities for a future mass casualty event. CASE SUMMARY: Our initial response targeted 3 general areas: staffing, supplies, and communication. Pharmacist and technician staffing was increased throughout the hospital, with a 6-fold increase of pharmacists to the emergency department (ED). To ensure adequate supplies were available, inventory on the ED automatic dispensing cabinets (ADC) was assessed for vaccines, antibiotics, and vasoactive medications. ED pharmacists prepared emergent intravenous medications in the ED while the sterile products room bolstered our supply of intravenous medications for patients in the ED and operating room. Overall, there was a 33% increase in the number of ADC transactions, with pharmacists representing 28% of all ADC transactions. To optimize communication, we formulated a comprehensive plan for the timely dissemination of information to the entire pharmacy staff. DISCUSSION: A mass casualty event is a rare occasion, and it is vital for the pharmacy department to respond rapidly with little notification. CONCLUSION: The role of a pharmacist is unique and can most effectively triage drug information and medication distribution, especially during times of high demand and high stress.

Impact of as Needed Heparin Boluses on Supratherapeutic Activated Partial Thromboplastin Time in Patients Managed With Extracorporeal Membrane Oxygenation.

INTRODUCTION: Brigham and Women's Hospital historically used titratable weight-based heparin nomograms with as needed boluses managed by extracorporeal membrane oxygenation specialists to achieve a predetermined goal-activated partial thromboplastin time (aPTT). Due to concern amongst providers that as needed boluses may lead to supratherapeutic aPTT's and subsequent bleeding, new nomograms without as needed boluses were implemented. The purpose of this retrospective observational analysis is to provide a comparison in safety and efficacy between the heparin nomograms with as needed boluses and the new nomograms without boluses. METHODS: Adult patients who were cannulated on extracorporeal membrane oxygenation and initiated on an approved heparin bolus nomogram (January 1, 2018-December 31, 2019) or an approved heparin no-bolus nomogram (October 20, 2020-March 31, 2021) were screened for inclusion. The major endpoint evaluated was the percentage of supratherapeutic aPTTs, defined as an aPTT above the upper limit of the specified nomogram goal, within the first 72 hours. RESULTS: A total of 23 patients were included in the bolus nomogram cohort and 9 patients in the no-bolus nomogram cohort. Within the first 72 hours of initiation, there were 11.5% supratherapeutic aPTTs in the bolus group and 5.1% in the no-bolus group ( P = 0.101). Overall there was 1 bleeding event in the no-bolus group (11.1%) and 7 in the bolus group (30.4%) ( P = 0.26). There were no thromboembolic events in either group. CONCLUSIONS: Overall, there was no difference found in the percentage of supratherapeutic aPTTs within the first 72 hours of heparin initiation between the bolus and no-bolus nomograms.

Electronic alerts to improve management of heparin-induced thrombocytopenia.

Background: Heparin-induced thrombocytopenia (HIT) is a difficult clinicopathologic diagnosis to make and to treat. Delays in identification and appropriate treatment can lead to increased morbidity and mortality. Objectives: To use electronic health alert interventions to improve provider diagnosis and management of heparin-induced thrombocytopenia through guideline-based, accurate care delivery. Methods: This quality improvement initiative developed 3 electronic health record-based interventions at our 750-bed academic medical center to improve the initial management of suspected HIT between 2018 and 2021: 1. an interruptive alert to recommend discontinuation of active heparin products when signing a heparin-platelet factor 4 test (PF4) order, 2. integrated 4T score calculation in the heparin-PF4 test order, and 3. interruptive alert suggesting not to order heparin-PF4 tests when the 4T score is <4. Changes in practice were assessed over defined time periods pre and post each intervention. Results: Intervention 1 resulted in heparin discontinuation in more patients, with 65% (191 heparin orders/293 heparin-PF4 enzyme-linked immunosorbent assay tests) of cases continuing heparin prealert and only 54% (127 heparin orders/235 heparin-PF4 enzyme-linked immunosorbent assay tests) postinterruptive alert (95% CI 2.3-19.9; P = .015). Intervention 2 increased appropriate heparin-PF4 test ordering from 40.4% (110/272) preintervention to 79.1% (246/311) (95% CI 30.9-46.4; P < .00001) postintervention, with inappropriate PF4 ordering defined as testing when 4T score was <4. Intervention 3 did not lead to reduction in heparin-PF4 testing in the control group (96 inappropriate orders/402 total orders, 24%) compared to the randomized alert group (56 inappropriate orders/298 total orders; 19%) (95% CI -1.2 to 11.5; P = .13). Conclusion: Implementation of unique electronic health record interventions, including both diagnostic and management interventions, led to improved guideline-based, accurate care delivery with 4T score calculation and cessation of heparin for patients with suspected HIT.

One-year retrospective analysis of anti-FXa apixaban and rivaroxaban levels demonstrates utility for management decisions in various urgent and nonurgent clinical situations.

OBJECTIVES: Quantification of direct oral anticoagulant (DOAC) plasma levels can guide clinical management, but insight into clinical scenarios surrounding DOAC-calibrated anti-FXa assays is limited. METHODS: Apixaban- and rivaroxaban-calibrated chromogenic anti-Xa assays performed over a 1-year period were retrospectively analyzed. Patient demographics, DOAC history, concomitant medications, and renal/liver comorbidities were obtained. Indications for testing and associated clinical actions were reviewed. Machine learning (ML) models predicting clinical actions were evaluated. RESULTS: In total, 371 anti-FXa apixaban and 89 anti-FXa rivaroxaban tests were performed for 259 and 67 patients in recurring urgent (acute bleeding, unplanned procedures) and nonurgent situations, including several scenarios not captured by existing testing recommendations (eg, drug monitoring, recurrent thromboembolic events, bleeding tendency). In urgent settings, andexanet reversal was guided by radiologic and clinical findings over DOAC levels in 14 of 32 instances, while 51% of apixaban patients qualified for nonreversal strategies through the availability of levels. Levels also informed procedure/intervention timing and supported management decisions when DOAC clearance or DOAC target levels were in question. The importance of clinical context was emphasized by exploratory ML models predicting particular clinical actions. CONCLUSIONS: Although clinical situations are complex, DOAC testing facilitates clinical decision-making, including reversal, justifying more widespread implementation of these assays.

Anticoagulation-Associated Adverse Drug Events in Hospitalized Patients Across Two Time Periods.

PURPOSE: Anticoagulants often cause adverse drug events (ADEs), comprised of medication errors and adverse drug reactions, in patients. Our study objective was to determine the clinical characteristics, types, severity, cause, and outcomes of anticoagulation-associated ADEs from 2015-2020 (a contemporary period following implementation of an electronic health record, infusion device technology, and anticoagulant dosing nomograms) and to compare them with those of a historical period (2004-2009). METHODS: We reviewed all anticoagulant-associated ADEs reported as part of our hospital-wide safety system. Reviewers classified type, severity, root cause, and outcomes for each ADE according to standard definitions. Reviewers also assessed events for patient harm. Patients were followed up to 30 days after the event. RESULTS: Despite implementation of enhanced patient safety technology and procedure, ADEs increased in the contemporary period. In the contemporary period, we found 925 patients who had 984 anticoagulation-associated ADEs, including 811 isolated medication errors (82.4%); 13 isolated adverse drug reactions (1.4%); and 160 combined medication errors, adverse drug reactions, or both (16.2%). Unfractionated heparin was the most frequent ADE-related anticoagulant (77.7%, contemporary period vs 58.3%, historical period). The most frequent anticoagulation-associated medication error in the contemporary period was wrong rate or frequency of administration (26.1%, n = 253), with the most frequent root cause being prescribing errors (21.3%, n = 207). The type, root cause, and harm from ADEs were similar between periods. CONCLUSIONS: We found that anticoagulation-associated ADEs occurred despite advances in patient safety technologies and practices. Events were common, suggesting marginal improvements in anticoagulant safety over time and ample opportunities for improvement.