Descriptive analysis evaluating the use of direct oral anticoagulation therapy in heart and lung transplant recipients.

BACKGROUND: Direct oral anticoagulants (DOACs) are widely utilized following cardiothoracic transplantation with limited guidance regarding drug-drug interactions (DDIs), periprocedural management, and DOAC-specific monitoring. METHODS: We performed a single-center, retrospective, descriptive analysis of adult cardiothoracic transplant recipients initiated on DOAC therapy between May 2016 and July 2021. The primary endpoint for this analysis was the percentage of patients dosed per package labeling. Secondary endpoints included DOAC prescribing in the context of DDIs, renal dysfunction, and periprocedural management, as well as thromboembolism and major bleeding at 12 months. RESULTS: A total of 125 patients were included in this analysis with a median age of 62 years. At initiation, 63.2% of patients were dosed according to package labeling. The most common reason for non-labeled dosing was concomitant azole antifungal therapy. DOAC therapy was held for 82 procedures with no reported thrombotic events and one major bleed in the setting of AKI. Hemodialysis-dependence was associated with a reduced risk of thrombosis (0 vs. 10 events per 100 PY, p = .002) and an increased risk of major bleeding (23 vs. 8 events per 100 PY, p = .006). Additionally, DOAC-specific anti-xa guided dosing was associated with a reduced risk of major bleeding (0 vs. 13 events per 100 PY, p < .001). CONCLUSION: Our findings show that deviation from package labeling is common following cardiothoracic transplantation and its association with clinical outcomes warrants further study.

Comparison of Sedation and Analgesia Requirements in Patients With SARS-CoV-2 Versus Non-SARS-CoV-2 Acute Respiratory Distress Syndrome on Veno-Venous ECMO.

BACKGROUND: Increased analgosedation requirements have been described in patients with acute respiratory distress syndrome (ARDS) on extracorporeal membrane oxygenation (ECMO) support due to unique pharmacokinetic challenges. There is a paucity of data comparing sedation requirements in patients on ECMO for ARDS secondary to SARS-CoV-2 versus other etiologies of respiratory failure. OBJECTIVE: To compare sedation and analgesia requirements in adult patients with SARS-CoV-2 versus non-SARS-CoV-2 ARDS requiring veno-venous (VV) ECMO support. METHODS: We performed a retrospective cohort study of adult patients receiving sedation and analgesia on VV-ECMO support. Patients were excluded if cannulated at an outside hospital for greater than 24 hours, expired within 48 hours of ECMO cannulation, or received neuromuscular blocking agents for greater than 7 consecutive days following ECMO cannulation. RESULTS: We evaluated 108 patients on VV-ECMO support, including 44 with non-SARS-CoV-2 ARDS and 64 with SARS-CoV-2 ARDS. The median daily dexmedetomidine requirements were significantly higher in the SARS-CoV-2 cohort (16.7 vs 13.4 mcg/kg/day, P = 0.03), while the median propofol daily requirements were significantly higher in the non-SARS-CoV-2 cohort (40.3 vs 53.5 mg/kg/day, P < 0.01). There was no difference in daily requirements of opioids, benzodiazepines, and ketamine between groups. Use of adjunct agents to facilitate weaning was significantly higher in the SARS-CoV-2 cohort (78.1% vs 43.2%, P < 0.01). CONCLUSION AND RELEVANCE: Patients with ARDS on VV-ECMO support require multiple analgosedative agents with concomitant use of nonparenteral adjunct agents. Further studies are needed to evaluate optimal analgosedation strategies in patients on ECMO support.

Pre-Existing Right Ventricular Dysfunction as an Independent Risk Factor for Post Intubation Cardiac Arrest and Hemodynamic Instability in Critically Ill Patients: A Retrospective Observational Study.

BACKGROUND: Post intubation cardiac arrest and hemodynamic instability are serious adverse events encountered in critically ill patients. The association of pre-existing right ventricular (RV) dysfunction with post intubation cardiac arrest and hemodynamic instability in critically ill patients is unknown. METHODS: This is a retrospective matched cohort study of adult critically ill patients who underwent intubation from July 2016 to December 2019. The study was conducted at a quaternary medical center in Houston, Texas. A total of 340 critically ill patients who underwent intubation in the intensive care units, wards, and the emergency room were included. The study cohort was categorized into 4 groups based on the pre-existing RV function: normal function, mild dysfunction, moderate dysfunction, and severe dysfunction. Cardiac arrest and/or hemodynamic instability within one hour post intubation were the primary study outcomes. Secondary outcomes included in hospital and 60-day mortality. RESULTS: Study patients were of mean age of 61.95 ± 14.28 years, including 132 (39%) females and 208 (61%) males. The primary outcomes were significantly worse in mild, moderate, and severe RV dysfunction groups compared to the normal RV function group (34.12%-P = 0.014, 47.06%-P < 0.001, 51.67%-P < 0.001, vs. 17.56%). In a multivariable logistic regression analysis, pre-existing moderate (OR = 2.65, P = 0.013) and severe RV dysfunction groups (OR = 2.66, P = 0.015) were associated with statistically significant higher cardiac arrest and hemodynamic instability post intubation. Pre-existing severe RV dysfunction was associated with statistically significant higher in hospital mortality (62.35%-P < 0.001). The multivariable Cox-regression analysis showed that pre-existing severe RV dysfunction was associated with a statistically significant higher 60-day mortality (HR = 2.57, P = 0.001). CONCLUSIONS: Pre-existing moderate and severe RV dysfunctions were independently associated with significantly higher cardiac arrest and/or hemodynamic instability post intubation in critically ill patients. Pre-existing RV function may serve as a mortality predictor in critically ill patients undergoing endotracheal intubation.

Approach to Sedation and Analgesia in COVID-19 Patients on Venovenous Extracorporeal Membrane Oxygenation.

OBJECTIVE: To describe clinically pertinent challenges of managing sedation in COVID-19 patients on venovenous extracorporeal membrane oxygenation (VV-ECMO) and describe considerations for enhanced safety and efficacy of pharmacological agents used. DATA SOURCES: A PubMed search was performed using the following search terms: ECMO, ARDS, sedation, COVID-19, coronavirus, opioids, analgesia, fentanyl, hydromorphone, morphine, oxycodone, methadone, ketamine, propofol, dexmedetomidine, clonidine, benzodiazepines, midazolam, lorazepam, and diazepam. STUDY SELECTION AND DATA EXTRACTION: Relevant clinical and pharmacokinetic studies were considered. All studies included were published between January 1988 and March 2021. DATA SYNTHESIS: Patients with acute respiratory distress syndrome secondary to COVID-19 may progress to requiring VV-ECMO support. Agents frequently used for sedation and analgesia in these patients have been shown to have significant adsorption to ECMO circuitry, leading to possible diminished clinical efficacy. Use of hydromorphone-based analgesia has been associated with improved clinical outcomes in patients on VV-ECMO. However, safety and efficacy regarding use of other agents in this patient population remains an area of further research. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review addresses clinical challenges associated with sedation management in COVID-19 patients requiring VV-ECMO support and provides potential strategies to overcome these challenges. CONCLUSIONS: Historically, sedation and analgesia management in patients requiring ECMO support have posed a challenge for bedside clinicians given the unique physiological and pharmacokinetic changes in this patient population. A multimodal strategy to managing analgesia and sedation should be used, and the use of enteral agents may play a role in reducing parenteral agent requirements.

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 Inhaled Alprostadil in Hospitalized Adult Patients.

BACKGROUND: Intermittent inhaled alprostadil (iPGE1) may be a viable alternative to inhaled nitric oxide or epoprostenol for management of right ventricular failure, pulmonary hypertension (pHTN) or acute respiratory distress syndrome (ARDS). However, limited evidence exists regarding iPGE1 use in adults, ideal dosing strategies, or optimal use cases. OBJECTIVE: To describe the clinical characteristics of patients receiving iPGE1 and identify specific sub-populations warranting further research. METHODS: This was a single-center, retrospective, descriptive analysis of inpatients who received at least one dose of iPGE1. The primary outcome was to describe patient characteristics and alprostadil dosing strategies. Secondary outcomes included changes in respiratory support requirements, hemodynamics, and inotropic/vasoactive use. Outcomes were stratified and compared based on primary therapeutic indication (cardiac or pulmonary). RESULTS: Fifty-four patients received iPGE1 40 (75%) for pulmonary (pHTN or ARDS) and 14 (25%) for cardiac indications. There was no difference between indications in the number of patients de-escalated from level of respiratory (53% vs 57%, P = 0.76), inotropic (70% vs 57%, P = 0.39), or vasopressor support (78% vs 57%, P = 0.17). Furthermore, there was no significant improvement in cardiopulmonary parameters at multiple time intervals after iPGE1 initiation. CONCLUSION AND RELEVANCE: This is the largest study to date on the use of intermittent iPGE1 in adults. Alprostadil was safely utilized in novel populations; however, efficacy as evaluated by clinical or surrogate endpoints could not be demonstrated and further investigation is needed to determine its potential and optimal place in therapy.

Apixaban and rivaroxaban anti-Xa level utilization for guidance of administration of andexanet alfa: a case series.

BACKGROUND: Andexanet alfa, a modified recombinant factor Xa (FXa), was FDA approved in 2018 for anticoagulant reversal in patients with life-threatening bleeding associated with FXa inhibitors (FXaI). The ANNEXA-4 investigators administered andexanet alfa to patients within an 18-h from last dose of oral FXaI. In practice, time from last dose is often unknown. Previous studies have shown that clearance of these agents may be impaired by renal and hepatic dysfunction, as well as drug-drug interactions. Decision for use of andexanet alfa is also complicated by its high cost, limited drug availability, and thrombotic risk. This study aimed to describe the utility of anti-Xa DOAC levels as a decision point to administer andexanet alfa. METHODS: This is a case series of four patients with an anti-Xa DOAC level that received andexanet alfa for oral FXaI reversal in the setting of life-threatening bleeding or prior to procedure. RESULTS: Four patients were included in the study. Two patients had a known time since last dose of oral FXaI. All patients had a detectable anti-Xa DOAC levels prior to administration of andexanet alfa. Two patients had levels within the peak range, one patient had a level below the peak range, and one patient had a level above the peak range. Andexanet alfa was administered after anti-Xa DOAC level return in all patients. CONCLUSION: In our case series, obtaining anti-Xa DOAC levels prior to administration of andexanet alfa was achievable and facilitated use of reversal agents in patients with major bleeding or emergent procedural need.

Hemodynamic Effects of Dexmedetomidine in Adults With Reduced Ejection Fraction Heart Failure.

BACKGROUND: Dexmedetomidine (DEX) can cause hypotension complicating its use in critically ill patients with labile hemodynamics secondary to an underlying disease state such as heart failure. The aim of this study was to determine the effect of DEX on mean arterial pressure (MAP) in nonsurgical patients with heart failure and reduced ejection fraction (HFrEF). METHODS: This retrospective single-center cohort study evaluated patients who received DEX in the cardiac care and medical intensive care units at a large academic hospital. The primary end point was the change in MAP within 6 hours following DEX initiation. RESULTS: Sixty-five patients with HFrEF diagnosis were compared 1:1 to a control group without HFrEF. Both groups experienced a decrease in MAP over the study period. Patients with HFrEF had a greater absolute percentage reduction in MAP 1 hour following DEX initiation compared to the control group (-9.6% vs -5.2%; P < .01). When accounting for the combined effect of DEX initiation and HFrEF diagnosis on the primary end point, patients with HFrEF did not have a significant difference in MAP compared to the control group over the study period. CONCLUSIONS: Within 6 hours following DEX initiation, both groups experienced a decrease in MAP. The effect of DEX on MAP over the composite time period was not found to be significantly different in the HFrEF group compared to the non-HFrEF group. However, patients with HFrEF experienced a greater reduction in MAP in the first hour following DEX initiation compared to the non-HFrEF group. Prospective studies are needed to evaluate the effect of DEX on patients with acute decompensated HFrEF compared to patients with compensated HFrEF.

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.

Second victim syndrome and the pharmacy learner.

This commentary describes the concept of second victim syndrome and its application to pharmacy learners and preceptors. Although there is published literature regarding implementation of second victim syndrome programs at an institutional level, there is limited guidance regarding the second victim syndrome in the context of a pharmacy training environment; however, there are known risk factors such as medication safety events, failure to rescue events, or overall lack of experience of a clinician. With a growing awareness of the mental health concerns of health care providers, this is a potential area for growth and skill development for pharmacists of all levels. As pharmacy leaders and role models, we have a fundamental ethical responsibility to take care of our learners, particularly when it comes to emotionally challenging patient care scenarios. By giving a name to what our learners may be experiencing, the second victim syndrome, we can progress toward improving the well-being of these learners and increase their ability to be effective pharmacists. Involvement with medication safety events or patients with negative outcomes has been shown to have adverse professional outcomes, and this article describes steps that can be taken by preceptors and peers to help facilitate professional growth and recovery. Second victim is an underappreciated phenomenon that can have a profound impact on pharmacists' well-being. Strategies for proactive recognition and intervention are vital.

Management of Anticoagulation with Impella® Percutaneous Ventricular Assist Devices and Review of New Literature.

Cardiogenic shock is a life-threatening condition that may occur secondary to a variety of cardiac conditions, and may require temporary support with percutaneous ventricular devices like the Impella®. Anticoagulation in patients with Impella® devices can often be complicated due to unpredictable purge flow rates, pre-existing coagulopathy, or heparin allergies. The purpose of this article is to discuss the various options for anticoagulation in the setting of Impella®. The article will also describe recent updates (2014-current) in literature surrounding anticoagulation therapy for Impella® devices. At total of 228 articles were initially obtained through the PubMed search, with inclusion of 6 articles. A total of 51 patients had data in the six studies that were included in the review. Heparin for anticoagulation in the purge solution, at two different dextrose concentrations (5% and 20%), was associated with similar therapeutic activated partial thromboplastin time rates, thrombotic and bleeding events. One case series described the use of argatroban in the purge solution for anticoagulation in two patients with suspected heparin-induced thrombocytopenia, without bleeding or thrombotic complications. Pump thrombosis was not reported in any of the six studies. Anticoagulation in the setting of mechanical circulatory support devices is a challenging aspect of critical care. Institutions should have set protocols that clearly define the options for anticoagulation. Future studies that look at longer durations of support and possible operation of the Impella® device with a heparin-free purge solution are needed.

A case series analysis of bicarbonate-based purge solution administration via Impella ventricular assist device.

PURPOSE: The Impella device historically required a heparin-based purge solution to reduce the risk of biomaterial deposition to maintain pump function. In April 2022, the Food and Drug Administration approved utilization of bicarbonate-based purge solutions (BBPS) as an alternative to heparin for patients who are intolerant to heparin or in whom heparin is contraindicated. The purpose of this case series is to report patient outcomes of Impella support with BBPS use at our institution. SUMMARY: Eighteen patients who received BBPS via the Impella CP or Impella 5.5 device were included in our review. Patients were included if they had BBPS administration for greater than 24 hours. All patients were followed for 72 hours after cessation of BBPS. Indications for BBPS were coagulopathy (n = 5, 28%), suspected HIT (n = 2, 11%), confirmed HIT (n = 1, 6%), and major bleeding (n = 10, 56%). Three patients (17%) experienced an Impella complication while on BBPS. One patient required pump exchange, one required removal of the Impella device, and one received alteplase for suspected purge block. Of these, two patients experienced complications greater than 21 days into BBPS therapy. CONCLUSION: This case series adds to the literature describing clinical outcomes for patients on Impella support with BBPS. While BBPS offers a viable option for the management of patients on Impella devices who are unable to tolerate heparin-based purge solutions, further data is needed to determine the longevity of the Impella device with BBPS to minimize risk of Impella complications.

Bloodstream infections in prolonged use of axillary-placed, intra-aortic balloon-pump support: A single-center study.

Infections from prolonged use of axillary intra-aortic balloon pumps (IABPs) have not been well studied. Bloodstream infection (BSI) occurred in 13% of our patients; however, no difference in outcome was noted between those with BSI and those without. Further studies regarding protocol developments that minimize BSI risk are needed.

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.

Updates in Hemodynamic Monitoring: A Review for Pharmacists.

Vital signs are regularly monitored in hospitalized patients. In the intensive care unit (ICU), traditional non-invasive blood pressure monitoring and telemetry may not provide enough information to determine the etiology of hemodynamic instability or guide intervention. Arterial catheters remain the gold-standard for continuous blood pressure monitoring and are commonly used in ICU patients. Pulmonary artery catheters and central venous catheters are beneficial in select patient populations and provide more advanced and specific information about a patient's hemodynamics. However, neither are benign and can increase risk of complications such as infection, arrhythmias, pneumothorax and vascular or valvular damage. In the past 10 years, the development of reliable non-invasive (NICOM), or minimally-invasive (MICOM), cardiac output monitoring devices has accelerated. The MICOM devices require an arterial catheter to obtain hemodynamic values, whereas NICOM devices do not require any arterial or venous access. These devices have emerged to be particularly useful in evaluating and managing patients with suspected mixed shock. As these devices become more prevalent, it is imperative that clinical pharmacists become familiar with interpreting this data as it may have a substantial impact on medication selection and optimization. This review will discuss the basics of NICOM and MICOM devices, limitations with these methods of monitoring, and clinical application for pharmacists.

Direct oral to parenteral anticoagulant transitions: Role of factor Xa inhibitor-specific anti-Xa concentrations.

OBJECTIVES: The increasing use of oral factor Xa inhibitors (FXaI) has led to a growing interest in the clinical utility of laboratory monitoring to enhance safety and effectiveness. Particularly, the use of FXaI-specific anti-Xa concentrations has gained traction and been advocated for several indications, but limited studies have explored the role of anti-Xa concentrations in guiding inpatient transitions from oral to parenteral anticoagulants. Therefore, additional data on such approaches are warranted to help balance bleeding and thrombotic risks in the higher acuity inpatient setting. This study sought to compare two strategies for oral-to-parenteral anticoagulant transitions: FXaI anti-Xa concentration-guided versus standard of care (i.e., per-package insert). STUDY DESIGN: This was an observational, single-center, retrospective cohort study conducted from May 2016 to May 2021. Hospitalized patients converted from an oral FXaI (apixaban or rivaroxaban) to therapeutic parenteral anticoagulation with or without FXaI anti-Xa concentration guidance were reviewed. The primary outcome of major bleeding, according to the International Society on Thrombosis and Hemostasis criteria, was compared between groups. Cox proportional hazard modeling was used to evaluate patient characteristics associated with major bleeding events. RESULTS: A total of 845 patients (388 in the concentration-guided group and 457 in the non-concentration-guided group) met the inclusion criteria. Major bleeding was significantly lower in the concentration-guided versus the non-concentration-guided group (2.2% vs. 11.3%; p < 0.001, respectively). There were no differences between the groups in thromboembolic complications (1.8% concentration guided vs. 1.5% non-concentration guided; p = 0.72) despite a significantly longer time from last oral FXaI dose to parenteral anticoagulant initiation in the concentration-guided group (27.9 h vs. 15.1 h; p < 0.01). The concentration-guided group had an 80% lower risk of major bleeding compared with the non-concentration-guided group (adjusted hazard ratio [HR] 0.20, 95% confidence interval [CI] 0.10-0.39; p < 0.01). CONCLUSIONS: This analysis suggests using FXaI anti-Xa concentrations to guide the transition from oral to parenteral anticoagulants may be beneficial in reducing major bleeds in select patient populations.

Direct Oral to Parenteral Anticoagulants: Strategies for Inpatient Transition.

The primary objective of this study was to describe the impact on bleeding rates of 2 different strategies for transitioning from a direct oral anticoagulant (DOAC) to a parenteral anticoagulant: a delayed, clinically driven strategy versus the standard per-package-insert strategy. This was a single-center descriptive cohort study conducted at a large academic medical center. Included patients were 18 years or older, admitted as an inpatient, and had received at least 1 dose of a DOAC prior to initiation of therapeutic parenteral anticoagulation. The primary end point was the incidence of major bleeds on the transition from a DOAC to a parenteral anticoagulant via a standard versus an intentionally delayed strategy. The secondary outcomes evaluated renal function, reason for delay, DOAC anti-factor Xa concentration, international normalized ratio values, blood product administration, and thrombotic complications. A total of 300 patients were included. The primary end point of bleeding was higher in the delayed group than the standard group, 25% and 12%, respectively (odds ratio, 0.39; P < .05). In both groups, patients who bled had a higher severity of illness, a greater incidence of acute kidney injury, and, when available, higher median DOAC anti-factor Xa concentrations. Despite a more conservative approach, patients in the delayed group experienced more bleeding, most likely attributable to a higher severity of illness, which highlights emerging challenges of inpatient anticoagulation management. Further prospective studies analyzing DOAC pharmacodynamics and pharmacokinetics in acutely ill patients are warranted.

Outcomes Associated With 4-Factor Prothrombin Complex Concentrate Administration to Reverse Oral Factor Xa Inhibitors in Bleeding Patients.

Compared with vitamin K antagonists (VKAs), oral factor Xa inhibitors are associated with at least equivalent efficacy and a lower incidence of major bleeding. Despite this benefit, bleeding remains the most common adverse event. Prior to the approval of andexanet alfa, alternative agents such as 4-factor prothrombin complex concentrate (4F-PCC) were utilized for reversal. This was a retrospective, descriptive study conducted on patients 18 years of age or older who received 4F-PCC for reversal of oral factor Xa inhibitors-associated bleeding. Patients were excluded if they received a VKA or dabigatran in the previous 48 hours. A subgroup analysis comparing 4F-PCC with andexanet alfa was conducted on patients who met the inclusion and exclusion criteria of the ANNEXA-4 trial. The primary end point of this study was to evaluate the incidence of hemostasis and associated dosing strategies in patients receiving 4F-PCC for reversal of oral factor Xa inhibitors-associated bleeding. Thirty-eight patients were included, and 28 patients (74%) achieved hemostasis. The median dose of 4F-PCC was 50 units/kg. In patients who achieved hemostasis, the median dose was 50 units/kg, and in those who failed to reach hemostasis, a median dose of 30 units/kg was seen. Within the subgroup analysis, there was no difference in overall rates of hemostasis between the 4F-PCC and andexanet alfa groups. Remaining a reasonable option to utilize for reversal of oral factor Xa inhibitors is 4F-PCC, especially when andexanet alfa is unavailable, with 50 units/kg appearing to be the most effective dose to achieve hemostasis. Further studies are needed to determine a preferential agent.

Anticoagulation in COVID-19: a review of current literature and guidelines.

Severe acute respiratory syndrome coronavirus 2 infections are associated with greater risk of both arterial and venous thromboembolic events.Pathophysiology and Clinical implications: This has been attributed to a florid proinflammatory state resulting in microvascular dysfunction, activation of platelets and procoagulant systems as well as possible direct endothelial injury. The associated morbidity and mortality of these events has prompted much speculation and varied anticoagulation and fibrinolytic strategies based on multiple criteria including disease severity and biomarkers. No clear definitive benefit has been established with these approaches, which have frequently led to greater bleeding complications without significant mortality benefit.Overview: In this review, we outline the burden of these thromboembolic events in coronavirus disease-2019 (COVID-19) as well as the hypothesized contributory biological mechanisms. Finally, we provide a brief overview of the major clinical studies on the topic, and end with a summary of major societal guideline recommendations on anticoagulation in COVID-19.

Use of Tissue Plasminogen Activator Alteplase for Suspected Impella Thrombosis.

BACKGROUND: Impella devices are being increasingly used to manage cardiogenic shock. The incidence of thrombosis and hemolysis in patients on Impella support increases with longer durations of use, and the management of Impella thrombosis remains ill-defined. METHODS: In this case series, we describe our institutional use of tissue plasminogen activator (tPA) alteplase in the Impella purge solution (0.04 or 0.08 mg/ml tPA in sterile water) for management of suspected Impella thrombosis in five patients, each with a different clinical course, treatment, and outcome. Given the limited evidence on the diagnosis of Impella thrombosis, suspicion was driven by the presence of decreased purge flow rates, increased purge pressures, and markers of hemolysis such as elevated lactate dehydrogenase and hematuria. OUTCOMES: In all cases, tPA administration resulted in resolution of low purge flow rates and high purge pressures. No major bleeding complications were directly associated with tPA. Two patients were bridged successfully to heart transplantation, two patients underwent left ventricular assist device implantation, and one patient died after withdrawal of care. CONCLUSION: Based on our experience, tPA administration appears to be a viable and safe salvage option to delay or prevent device exchange in the setting of suspected Impella thrombosis.