Faculty Bibliography

OBJECTIVES/OBJECTIVE:The rate of thromboembolic events among patients with coronavirus disease 2019 is high; however, there is no robust method to identify those at greatest risk. We reviewed thromboelastography studies in critically ill patients with coronavirus disease 2019 to characterize their coagulation states. DESIGN/METHODS:Retrospective. SETTING/METHODS:Tertiary ICU in New York City. PATIENTS/METHODS:Sixty-four patients with coronavirus disease 2019 admitted to the ICU with thromboelastography performed. INTERVENTIONS/METHODS:None. MEASUREMENTS AND MAIN RESULTS/RESULTS:Fifty percent of patients had a clotting index in the hypercoagulable range (clotting index > 3) (median 3.05). Reaction time and K values were below the lower limit of normal in 43.8% of the population consistent with a hypercoagulable profile. The median α angle and maximum amplitude (75.8° and 72.8 mm, respectively) were in the hypercoagulable range. The α angle was above reference range in 70.3% of patients indicative of rapid clot formation. Maximum amplitude, a factor of fibrinogen and platelet count and function, and a measure of clot strength was above reference range in 60.1% of patients. Thirty-one percent had thromboembolic events; thromboelastography parameters did not correlate with events in our cohort. Those with D-dimer values greater than 2,000 were more likely to have shorter reaction times compared with those with D-dimer levels less than or equal to 2,000 (4.8 vs 5.6 min; p = 0.001). CONCLUSIONS:A large proportion of critically ill patients with coronavirus disease 2019 have hypercoagulable thromboelastography profiles with additional derangements related to fibrinogen and platelet function. As the majority of patients have an elevated thromboelastography maximum amplitude, a follow-up study evaluating platelet aggregation would be instructive.

BACKGROUND/UNASSIGNED:Recombinant factor VIIa (rFVIIa) (Novoseven®) is utilized for the reversal of anticoagulation-associated bleeding and refractory bleeding in cardiac surgery. In August 2015, rFVIIa was transferred from the blood bank to the pharmacy at New York University (NYU) Langone Health. Concordantly, an off-label dosing guideline was developed. The objective of this study was to describe utilization and cost of rFVIIa and assess compliance to our dosing guideline. METHODS/UNASSIGNED:We performed a retrospective, observational review of rFVIIa administrations post-implementation of an off-label dosing guideline. All patients who received rFVIIa between September 2015 and June 2017 were evaluated. For each rFVIIa administration, anticoagulation and laboratory values, indications for use, dosing, ordering and administration times, concomitant blood products, and adverse events were collected. Adverse events included venous thromboembolism, stroke, myocardial infarction, and death due to systemic embolism and mortality. The primary endpoint was the utilization of rFVIIa in accordance with the off-label dosing guideline. Secondary endpoints included hemostatic efficacy of rFVIIa, adverse events, blood products administered, and cost-effectiveness of rFVIIa transition to pharmacy. RESULTS/UNASSIGNED: = 57)] received rFVIIa, with the majority of use for refractory bleeding after cardiac surgery. The utilization of rVIIa decreased after development of the off-label dosing guideline and transition from blood bank to pharmacy. The total incidence of thromboembolic events within 30 days was 19.6%; 17.6% arterial and 2% venous; 70% of patients with an adverse event were over 70 years of age. Use of rFVIIa reduced the median number of units of blood products administered. CONCLUSION/UNASSIGNED:Administration of rFVIIa for cardiac surgery appears to be effective for hemostasis. Transitioning rFVIIa from the blood bank to pharmacy and implementation of a dosing guideline appears to have reduced utilization. Patients receiving rFVIIa should be monitored for thromboembolic events. Elderly patients may be at higher risk for thromboembolic events.

BACKGROUND:Oral factor Xa inhibitors (OFXais) may interfere with the heparin antifactor Xa (antiXa) assay. The best method to measure heparin activity during the transition from an OFXai to intravenous (IV) unfractionated heparin (UFH) remains unknown. This study aimed to assess the safety and effectiveness of transitioning from an OFXai to UFH. METHODS:A retrospective analysis was conducted of patients with supratherapeutic antiXa levels on UFH who received either apixaban or rivaroxaban within 72 h prior to UFH initiation at NYU Langone Health (NYULH). The primary objective was to identify the incidence of interference on the heparin antiXa assay due to OFXai exposure in the previous 72 h. The secondary outcomes included the indication for transition to UFH and the rate of thromboembolic and bleeding events. RESULTS:A total of 93 patients with supratherapeutic antiXa activity levels with prior OFXai use were reviewed. Moderate renal impairment, defined as CrCl less than 49 mL/min, was present in 67 (72%) patients. The primary indication for transition from OFXai to UFH was in anticipation for a procedure, and it occurred in 37 (40%) patients. There were three major bleeding events and three clinically relevant non-major bleeding events. No thromboembolic events occurred. CONCLUSIONS:This study assessed the prevalence of supratherapeutic antiXa levels and clinical outcomes during the transition from OFXais to UFH. Healthcare systems should develop guidelines to assist clinicians in monitoring antiXa activity in patients undergoing a transition from an OFXai to UFH. It is also important to assess the patient's underlying thromboembolic and bleeding risks.

Background and Purpose/UNASSIGNED:The ideal dosing regimen of 4-factor prothrombin complex concentrate (4FPCC) after warfarin-induced intracranial hemorrhage (WICH) remains unclear. We sought to compare the safety and efficacy of the 4FPCC package insert dosing strategy (standard dose [SD]) with our institutional guideline for high-dose (HD) 4FPCC for patients with WICH. Methods/UNASSIGNED:We compared the percentage of SD and HD patients who achieved an international normalized ratio (INR) ≤1.3 at a single institution between January 2014 and July 2017. Additionally, we assessed hematoma expansion, recurrence of INR > 1.3, and occurrence of thrombotic events within 7 days of 4FPCC administration. Results/UNASSIGNED:= .243). Conclusions/UNASSIGNED:High-dose 4FPCC appears to be more effective at lowering INR and preventing bleed expansion in patients with WICH, while maintaining a similar safety profile.

INTRODUCTION/BACKGROUND:Hypoglycemia is a common adverse effect when intravenous (IV) insulin is administered for hyperkalemia. A prolonged infusion of dextrose 10% (D10) may mitigate hypoglycemia compared to dextrose 50% (D50) bolus. Our objective was to evaluate whether D10 infusion is a safe and effective alternative to D50 bolus for hypoglycemia prevention in hyperkalemic patients receiving IV insulin. METHODS: > 5.5) and received IV insulin and D10 infusion or D50 bolus within 3 h. The primary endpoint was incidence of hypoglycemia, defined as blood glucose (BG) ≤ 70 mg/dL, in the 24 h following IV insulin administration for hyperkalemia. RESULTS:A total of 134 patients were included; 72 in the D50 group and 62 in the D10 group. There was no difference in incidence of hypoglycemia between the D50 and D10 groups (16 [22%] vs. 16 [26%], p = 0.77). Symptomatic hypoglycemia, severe hypoglycemia, and hyperglycemia rates in the D50 and D10 groups were [5 (7%) vs. 2 (3%), p = 0.45], [5 (7%) vs. 1 (2%), p = 0.22], and [34 (47%) vs. 23 (37%), p = 0.31] respectively. Low initial BG was a predictor for developing hypoglycemia. CONCLUSIONS:In our study, D10 infusions appeared to be at least as effective as D50 bolus in preventing hypoglycemia in hyperkalemic patients receiving IV insulin. In context of ongoing D50 injection shortages, D10 infusions should be a therapeutic strategy in this patient population.

Andexanet-alpha is a specific reversal agent for direct factor Xa inhibitors (dFXaI). We aimed to project utilization rates and cost of andexanet for reversal of dFXaI-related major hemorrhage compared to 4-factor prothrombin complex concentrates (4F-PCC). A retrospective, multicenter review was conducted between 1/1/2014 and 7/15/2018 of patients who received 4F-PCC for reversal of dFXaI-related life-threatening hemorrhages. Total hospital reimbursements/patient were calculated based on national average MS-DRG payments adjusting for Medicare discounts. The projected cost for andexanet (based on dose and insurance) and % reimbursement/patient was compared to the actual cost of 4F-PCC. Hemostasis at 24 h (excellent/good vs. poor) and 30-day thrombotic complications were assessed. Of 126 patients who received 4F-PCC to reverse dFXaI, 46 (~ 10 per-year) met inclusion criteria. The median projected cost of andexanet was $22,120/patient, compared to $5670/patient for 4F-PCC (P < 0.001). The median hospital reimbursement was $11,492/hospitalization. The projected cost of andexanet alone would exceed the entire hospital reimbursement in 74% of patients by a median of $7604, while 4F-PCC cost exceeded the total hospital payments in 7% of patients in the same cohort (P < 0.001). Hemostasis was excellent/good in 72% of patients post-4F-PCC, compared to 82% in andexanet trials. Thromboembolic events occurred in 4% of patients following 4F-PCC versus 10% in andexanet trials. The projected cost of andexanet would exceed the national average hospital reimbursement/patient in nearly 75% of patients by over $7500/hospitalization. 4F-PCC was significantly less expensive, had lower rates of thrombosis, but also lower rates of good/excellent hemostasis compared to published data for andexanet.

Antithrombotic therapy for stroke prevention in patients with atrial fibrillation (AF) has dramatically shifted from warfarin, a vitamin K antagonist, to the direct oral anticoagulants (DOACs) such as dabigatran, apixaban, and rivaroxaban. In patients with contraindications to oral anticoagulation, left atrial appendage occlusion (LAAO) devices, such as the Watchmanâ„¢ device, may be considered; however, temporary postimplantation antithrombotic therapy is still a recommended practice. We present a case of complex antithrombotic management, post LAAO device implantation, designed to avoid drug interactions with concomitant rifampin use and remained necessary secondary to subsequent device leak. This case highlights the challenges of antithrombotic therapy post LAAO device placement in a complex, but representative, patient.

Although Candida species are common pathogens for nosocomial infections, Candida endocarditis is still considered a rare entity. Here, we report two cases of Candida parapsilosis endovascular infections in patients with prosthetic valves, both of which responded to combination antifungal therapy without surgical intervention. Additionally, T2 magnetic resonance (T2MR) was used to assess for resolution of invasive candidiasis. The first case is of an elderly man with Candida parapsilosis endovascular infection who responded to combination antifungal therapy with micafungin and fluconazole followed by suppressive therapy, without surgical intervention. The second case is of a middle-aged man with Candida parapsilosis prosthetic valve endocarditis who also responded to combination antifungal therapy with micafungin, flucytosine and fluconazole, without surgical intervention.

Objective Patients with acute myelogenous leukemia or myelodysplastic syndrome undergoing induction chemotherapy are at increased risk of invasive fungal infection due to prolonged, severe neutropenia. Due to this risk, national guidelines recommend invasive fungal infection prophylaxis in this population until the resolution of neutropenia. Although posaconazole has demonstrated superiority over fluconazole and itraconazole, there is limited evidence for voriconazole for invasive fungal infection prophylaxis in this population. Even less data are available comparing posaconazole and voriconazole directly. The study objective was to investigate the efficacy and safety of delayed-release posaconazole tablets versus voriconazole for primary invasive fungal infection prophylaxis. The primary outcome was rate of discontinuation of either agent. Secondary outcomes included specific rates of discontinuation due to adverse events and drug-drug interactions, rates of breakthrough invasive fungal infection, and 30-day and 100-day mortality rates. Methods This was a retrospective cohort study of adult patients admitted to NYU Langone Health between 1 January 2014 and 31 August 2017 and initiated on invasive fungal infection prophylaxis during induction or reinduction chemotherapy for acute myelogenous leukemia or myelodysplastic syndrome. Results In total, 77 patients were included in the study: 43 using posaconazole delayed-release tablets and 34 using oral voriconazole. In the posaconazole group, 30% of patients (n = 13) discontinued therapy for any reason compared with 35% (n = 12) of patients in the voriconazole group (p = 0.64). A higher percentage of patients in the voriconazole group discontinued due to adverse events (6 patients, 18% vs. 1 patient, 2%, p = 0.04). Mortality rates at 30 and 100 days were similar between both groups. No breakthrough invasive fungal infections was noted in either group. Conclusion Overall, discontinuations for any reason were similar in patients taking both posaconazole delayed-release and oral voriconazole. Both posaconazole delayed-release tablets and oral voriconazole appear to be effective at preventing invasive fungal infection in acute myelogenous leukemia and myelodysplastic syndrome patients undergoing induction chemotherapy, although posaconazole may be more tolerable.