Clinical Pathways and Outcomes of Andexanet Alfa Administration for the Reversal of Critical Bleeding in Patients on Oral Direct Factor Xa Inhibitors.

Background Andexanet is U.S. Food and Drug Administration (FDA) approved for the reversal of critical bleeding from factor Xa inhibitors and off-label for surgical reversal. Data are lacking on andexanet administration processes. Methods We retrospectively studied patients at a 23-hospital system who received andexanet from November 2019 to March 2023. Abstractors coded demographics, comorbidities, anticoagulant use, andexanet indication, and process times. The primary outcome was presentation-to-andexanet time; diagnosis, ordering, and administration times were calculated. Secondary outcomes included in-hospital postandexanet major thromboembolism/bleeding and mortality. Results In total, 141 patients were analyzed. Andexanet indications were predominantly neurologic bleeding (85.8%). Twenty-four patients (17.0%) were transferred from nontertiary/academic centers to tertiary/academic centers. The median presentation-to-administration time was 192.5 minutes (interquartile range [IQR]: 108.0-337.0 minutes). Components were as follows: 72.5 minutes (IQR: 39.0-137.5 minutes) for bleeding diagnosis; 35.5 minutes (IQR: 0-96.5 minutes) for andexanet ordering; and 53.0 minutes (IQR: 38.5-78.5 minutes) for administration, which was longer at tertiary/academic hospitals (ratio 1.5, 95% confidence interval [CI]: 1.2-2.0, p = 0.002). Gastrointestinal or other critical bleeding (ratio 2.59, 95% CI: 1.67-4.02, p < 0.001), and tertiary/academic center treatment (ratio 1.58, 95% CI: 1.15-2.18, p = 0.005), were associated with increased time. Major thromboembolism, bleeding, and mortality occurred in 10.6, 12.0, and 22.9% of patients, respectively. Conclusions In our cohort, the median presentation-to-administration time was over 3 hours. Cumulative times were longer at tertiary/academic hospitals and for gastrointestinal/other bleeding. Postandexanet major thromboembolism/bleeding occurred more at tertiary/academic hospitals, possibly related to transfers. Prospective studies may elucidate clinical decision-making bottlenecks.

Methemoglobinemia in the Era of COVID-19: A Potential Confounder of Glycemic Control.

Glycated hemoglobin A1c (HbA1c) is frequently used as a measure of glycemic control but can be inaccurate in certain clinical scenarios leading to poor estimates of insulin requirements. We present the case of a 76-year-old man with diabetes and COVID infection. HbA1c was measured at 5.7%, though the patient reported home glucose readings of 200 to 300 mg/dL (11.1-16.65 mmol/L). Pulse oximetry on presentation was 50% to 60%, which initially improved to 93% with supplemental oxygen of 15 L via nonrebreather face mask. Treatment with remdesivir and dexamethasone was initiated, but the patient was again found to have low oxygen saturations requiring bilevel positive airway pressure and transfer to the intensive care unit. The patient was started on 1.1 U/kg of insulin daily in a basal-bolus regimen. The patient developed severe hyperglycemia requiring 2.4 U/kg to achieve glycemic control. Co-oximeter analysis of an arterial blood gas sample revealed methemoglobinemia. Exchange transfusion was performed with clinical improvement. Subsequent measurement of fructosamine was 360 umol/L (360 000 µmol/L), correlating with reported home glucose measurements. Methemoglobinemia may impair glycation of hemoglobin or interfere with measurement of HbA1c, thereby compromising the use of this molecule as a marker for glycemic control in patients with this condition.

Characteristics of the post-surgical decrease in platelet counts in orthopedic surgery patients, observations and insights.

INTRODUCTION: A reduced platelet count (PLT) is a frequent post-operative finding in orthopedic surgery patients. Despite its prevalence, the characteristics of post-surgical thrombocytopenia have not been well described. METHODS: A retrospective chart review was conducted on patients who underwent a knee or hip replacement from 2012 to 2015. Patients who received heparin were excluded. RESULTS: A total of 56 patients were analyzed on post-operative days 0 to 4. By day 1, 90.9% of the patients experienced a reduction in their platelet counts. The lowest mean platelet count (nadir) occurred on day 2 (201.3 × 109/L). The average decrease in the platelet count from the baseline was 24% (95%CI: 20.6 - 27.2). The change in the platelet count from the baseline ranged from a 49.6% drop to a 14.2% increase. A substantial portion of patients experienced thrombocytopenia, with 28% occurring on day 2. Platelet counts less than 100 × 109/L occurred only once. The percent decrease in the platelet count from the baseline to any other time point was significantly larger in patients aged > 65 years, compared to patients aged ≤ 65 years (p = 0.007). Specifically, the average drop in the platelet count at the nadir (day 2) relative to the baseline was 27.8% in patients aged > 65 years, compared to 19.5% in patients aged ≤ 65 years. CONCLUSIONS: A reduction in the platelet count is a frequent post-operative finding in orthopedic surgery patients, even after removing confounding factors, such as heparin exposure, but clinical thrombocytopenia is uncommon. Alternative etiologies should be considered when the platelet count is less than 100 × 109/L. Vigilance should also be considered regarding elderly patients.

Necrotic herpes simplex lymphadenitis imitating Richter's transformation in a patient with chronic lymphocytic leukemia - A case report.

Richter Transformation (RT) is the phenomenon of progression from Chronic Lymphocytic Leukemia (CLL) into an aggressive Large-Cell Lymphoma and is typically characterized by diffuse lymphadenopathy combined with the classical "B symptoms". While rare, other causes of sudden onset diffuse lymphadenopathy in patients with CLL can occur; one of the rarest being necrotic herpes simplex lymphadenitis. We report a case that presented similarly to Richter Transformation including PET-CT scan findings consistent with RT but was histologically proven to be necrotic herpes simplex lymphadenitis. We identified less than 20 reported cases of this phenomenon in English language literature. Our patient was successfully treated with appropriate antiviral therapy due to timely recognition of the correct disease process. Our case reinforces the importance of maintaining diagnostic suspicion when approaching sudden onset lymphadenitis in this patient population.

Progressively confluent monkeypox lesions with necrosis.

Human monkeypox virus became a burgeoning global health issue when outbreaks were identified in over 100 countries beginning in early 2022. We describe the case of a 38-year-old male with acquired immunodeficiency syndrome who presented one month after the development of painful anal lesions, subsequently confirmed to be monkeypox. The patient was unsuccessfully treated outpatient with multiple courses of oral tecovirimat before presenting to the emergency department for continual lesion progression. Given his AIDS, the patient was at-risk for poor response to oral treatment due to the potential for malabsorption from disruptions in his gut microbiome as well as inability to consume the recommended 25 grams of fat per dose needed for absorption. The identification of patients at-risk for severe disease is imperative as this population may be better suited for intravenous tecovirimat treatment due to the difficult parameters required for optimal absorption of oral therapy.

Universal EHRs Clinical Decision Support for Thromboprophylaxis in Medical Inpatients: A Cluster Randomized Trial.

Background: Thromboprophylaxis for medically ill patients during hospitalization and postdischarge remains underutilized. Clinical decision support (CDS) may address this need if embedded within workflow, interchangeable among electronic health records (EHRs), and anchored on a validated model. Objectives: The purpose of this study was to assess the clinical impact of a universal EHR-integrated CDS tool based on the International Medical Prevention Registry on Venous Thromboembolism plus D-Dimer venous thromboembolism model. Methods: This was a cluster randomized trial of 4 tertiary academic hospitals from December 21, 2020 to January 21, 2022. Inpatients over age 60 with key medical illnesses were eligible. We embedded CDS at admission and discharge. Hospitals were randomized to intervention (CDS; n = 2) vs usual care (n = 2) groups. The primary outcome was rate of appropriate thromboprophylaxis. Secondary outcomes included venous, arterial, and total thromboembolism, major bleeding, and all-cause mortality through 30 days postdischarge. Results: After exclusions, 10,699 of 19,823 patients were analyzed. Intervention group tool adoption was 77.8%. Appropriate thromboprophylaxis was increased at intervention hospitals, both inpatient (80.1% vs 72.5%, OR: 1.52, 95% CI: 1.39-1.67) and at discharge (13.6% vs 7.5%, OR: 1.93, 95% CI: 1.60-2.33). There were fewer venous (2.7% vs 3.3%, OR: 0.80, 95% CI: 0.64-1.00), arterial (0.25% vs 0.70%, OR: 0.35, 95% CI: 0.19-0.67), and total thromboembolisms (2.9% vs 4.0%, OR: 0.71, 95% CI: 0.58-0.88) at intervention hospitals. Major bleeding was rare and did not differ between groups. Mortality was higher at intervention hospitals (9.1% vs 7.0%, OR: 1.32, 95% CI: 1.15-1.53). Conclusions: EHR-embedded CDS increased appropriate thromboprophylaxis and reduced thromboembolism without increasing major bleeding in medically ill inpatients. Mortality was higher at intervention hospitals.