Faculty Bibliography

PURPOSE:To describe our medical center's pharmacy services preparedness process and offer guidance to assist other institutions in preparing for surges of critically ill patients such as those experienced during the coronavirus disease 2019 (COVID-19) pandemic. SUMMARY:The leadership of a department of pharmacy at an urban medical center in the US epicenter of the COVID-19 pandemic proactively created a pharmacy action plan in anticipation of a surge in admissions of critically ill patients with COVID-19. It was essential to create guidance documents outlining workflow, provide comprehensive staff education, and repurpose non-intensive care unit (ICU)-trained clinical pharmacotherapy specialists to work in ICUs. Teamwork was crucial to ensure staff safety, develop complete scheduling, maintain adequate drug inventory and sterile compounding, optimize the electronic health record and automated dispensing cabinets to help ensure appropriate prescribing and effective management of medication supplies, and streamline the pharmacy workflow to ensure that all patients received pharmacotherapeutic regimens in a timely fashion. CONCLUSION:Each hospital should view the COVID-19 crisis as an opportunity to internally review and enhance workflow processes, initiatives that can continue even after the resolution of the COVID-19 pandemic.

Background: Fondaparinux is FDA-approved for prophylaxis of venous thromboembolism (VTE) in patients undergoing surgery as well as for the treatment of acute deep vein thrombosis and pulmonary embolism. Off-label, fondaparinux is used as an alternative to argatroban in the treatment of suspected or confirmed heparin-induced thrombocytopenia (HIT). The Antithrombotic/Hemostatic Stewardship Committee at NYU Langone Health (NYULH) provides guidance for the safe and effective use of fondaparinux, while assuring that an evidenced-based and cost-effective approach for utilization is maintained.
Aim(s): To evaluate the utilization of fondaparinux at NYULH and to assess guideline adherence, efficacy, safety, and cost avoidance.
Method(s): This was a retrospective review of adult patients who received fondaparinux between November 2016 and June 2019 at NYULH. The primary outcome was assessment of fondaparinux utilization based on the dosing guideline. Secondary outcomes included tolerability, safety, and cost-avoidance.
Result(s): Ninety-eight patients received fondaparinux, with the most frequent indications being suspected HIT (44%), VTE prophylaxis (23%), and continuation of home therapy (14%). Based on the NYULH fondaparinux dosing guideline, 97 (99%) patients were dosed appropriately. One patient (1%) received fondaparinux while on hemodialysis. Thromboembolic events occurred in 3 (3%) patients, major bleeding occurred in 4 (4%) patients and clinically relevant non-major bleeding occurred in 2 (2%) patients. In the 52 patients with suspected or confirmed HIT, the cost-avoidance of utilizing fondaparinux instead of argatroban was approximately $100,000.
Conclusion(s): The majority of fondaparinux utilization at NYULH is for suspected HIT, and dosing guidelines were followed in most cases. A low thromboembolic event rate with the use of fondaparinux was observed. The major and clinically relevant non-major bleeds experienced in six patients may be attributed to these patients' baseline high bleeding risk. Fondaparinux was a cost-effective alternative to argatroban in patients with suspected or confirmed HIT in this patient population. (Table Presented)

Introduction. COVID-19 has rapidly emerged as a pandemic infection that has caused significant mortality and economic losses. Potential therapies and prophylaxis against COVID-19 are urgently needed to combat this novel infection. As a result of in vitro evidence suggesting zinc sulphate may be efficacious against COVID-19, our hospitals began using zinc sulphate as add-on therapy to hydroxychloroquine and azithromycin.Aim. To compare outcomes among hospitalized COVID-19 patients ordered to receive hydroxychloroquine and azithromycin plus zinc sulphate versus hydroxychloroquine and azithromycin alone.Methodology. This was a retrospective observational study. Data was collected from medical records for all patients with admission dates ranging from 2 March 2020 through to 11 April 2020. Initial clinical characteristics on presentation, medications given during the hospitalization, and hospital outcomes were recorded. The study included patients admitted to any of four acute care NYU Langone Health Hospitals in New York City. Patients included were admitted to the hospital with at least one positive COVID-19 test and had completed their hospitalization. Patients were excluded from the study if they were never admitted to the hospital or if there was an order for other investigational therapies for COVID-19.Results. Patients taking zinc sulphate in addition to hydroxychloroquine and azithromycin (n=411) and patients taking hydroxychloroquine and azithromycin alone (n=521) did not differ in age, race, sex, tobacco use or relevant comorbidities. The addition of zinc sulphate did not impact the length of hospitalization, duration of ventilation or intensive care unit (ICU) duration. In univariate analyses, zinc sulphate increased the frequency of patients being discharged home, and decreased the need for ventilation, admission to the ICU and mortality or transfer to hospice for patients who were never admitted to the ICU. After adjusting for the time at which zinc sulphate was added to our protocol, an increased frequency of being discharged home (OR 1.53, 95 % CI 1.12-2.09) and reduction in mortality or transfer to hospice among patients who did not require ICU level of care remained significant (OR 0.449, 95 % CI 0.271-0.744).Conclusion. This study provides the first in vivo evidence that zinc sulphate may play a role in therapeutic management for COVID-19.

OBJECTIVE:<0.001). Rates of adverse events increased with the magnitude of D-dimer elevation; individuals with presenting D-dimer >2000 ng/mL had the highest risk of critical illness (66%), thrombotic event (37.8%), acute kidney injury (58.3%), and death (47%). CONCLUSIONS:Abnormal D-dimer was frequently observed at admission with COVID-19 and was associated with higher incidence of critical illness, thrombotic events, acute kidney injury, and death. The optimal management of patients with elevated D-dimer in COVID-19 requires further study.

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.