Andexanet Alfa for Specific Anticoagulation Reversal in Patients with Acute Bleeding during Treatment with Edoxaban

Background Andexanet alfa (andexanet) is approved for specific anticoagulation reversal in patients with life-threatening or uncontrolled bleeding during treatment with rivaroxaban or apixaban. There is limited experience with andexanet in patients with acute bleeding on edoxaban. Methods Patients with acute major bleeding within 18 hours of edoxaban intake were prospectively enrolled. Patients received a bolus and 2-hour follow-on infusion of andexanet. The co-primary efficacy outcomes were change in antifactor Xa activity and the percentage of patients achieving excellent or good hemostasis, 12 hours after andexanet treatment. Efficacy was analyzed in patients with confirmed major bleeding and baseline antifactor Xa activity ≥40 ng/mL. Safety was analyzed in all patients. Results Thirty-six patients (mean age: 82 years, 61.1% male and 91.7% with atrial fibrillation) with acute major bleeding on edoxaban received andexanet. The primary site of bleeding was intracranial in 29 patients (80.6%). In the efficacy population (n = 28), median antifactor Xa activity decreased from 121.1 (interquartile range [IQR]: 70.3–202.4) ng/mL at baseline to 24.0 (IQR: 77.7–83.7) ng/mL at the end of andexanet bolus (median decrease: 68.9%, 95% confidence interval [CI]: 56.1–77.7%). Excellent or good hemostasis at 12 hours was achieved in 78.6% (95% CI: 59.0–91.7%) of patients. Within 30 days, four patients (11.1%) experienced a thrombotic event and four others (11.1%) died. Conclusion In patients with acute major bleeding on edoxaban, andexanet significantly decreased antifactor Xa activity. Hemostatic efficacy was similar to that observed in patients with bleeding on rivaroxaban or apixaban. Thrombotic events occurred at a rate expected in such patients.

The impact of trans-arterial embolization on the result of chemoradiotherapy in oral cavity cancer

Objectives: Evaluation of the hemostatic effect of trans-arterial embolization on patients with advanced oral cavity cancer who had bleeding complications while undergoing definitive concurrent chemoradiotherapy (CCRT). Additionally, assess the effect of trans-arterial embolization on treatment response following concurrent chemoradiotherapy, as well as overall survival (OS) and progression-free survival (PFS) in the group of patients following the intervention. Method: From September 2018–June 2021, a retrospective descriptive study was conducted on 16 patients with inoperable, locally advanced oral cavity cancer who received definitive concurrent chemoradiotherapy, experienced acute bleeding complications, and received selective intravascular intervention with various embolization materials at Vietnam National Cancer Hospital. Results: After selective embolization, 16/16 patients ceased bleeding; 1 patient re-bled for the second time after 3 weeks. The average duration of chemoradiotherapy interruption due to intervention was 6.7 days. After CCRT, 15/16 (93.75%) patients achieved a response, with 9/16 (56.25%) patients achieving a complete response. The median OS was 14 months (range, 3–26 months), and the median PFS was 10 months (range, 3–20 months). There were no significant complications, particularly neurological side effects. ConclusionsTumor bleeding is a common and serious complication of CCRT treatment in patients with locally advanced oral cavity cancer. Embolization is a safe and effective method of controlling acute bleeding that has no adverse effect on the outcome of definitive concurrent chemoradiotherapy.

Real-World Data of the Hemostatic Efficacy of Recombinant Human Factor VIIa Eptacog Beta for Acute Bleeding Events in Patients with Hemophilia a and B with Inhibitors

Introduction: Activated prothrombin complex concentrate (FEIBA, Takeda) and recombinant factor VIIa (rFVIIa, Novoseven, NovoNordisk) remain the primary bypassing agents (BPA) available for bleeding management in patients with hemophilia and inhibitors. Eptacog beta [rFVIIa-B, Coagulation factor VIIa (recombinant)-jncw, Sevenfact, HEMA Biologics & LFB] is a recombinant human FVIIa approved by the FDA in 2020 for the treatment of acute bleeding events in adult and adolescent patients ≥12 years old with hemophilia A or B with inhibitors. rFVIIa-B demonstrated hemostatic efficacy of 86% in a phase 3, randomized cross-over study of 465 mild/moderate bleeding events in 27 patients with hemophilia A and B with inhibitors. The purpose of this study is to report real-world data on the hemostatic efficacy of rFVIIa-B for acute bleeding management in patients with hemophilia A and B with inhibitors. Methods: This is a retrospective chart-review of individuals ≥12 years of age with severe hemophilia A (factor VIII <1%) or hemophilia B (factor IX <1%) with an active inhibitor from 3 U.S. hemophilia treatment centers who utilized rFVIIa-B for acute bleed management. Results: Seven bleeds were treated among the 3 patients identified. Patient characteristics and bleeding events are summarized in Table 1. The 3 patients were 12, 13, and 31 years of age. Two patients had hemophilia A and 1 patient had hemophilia B. The 2 patients with hemophilia A were on emicizumab prophylaxis per standard dosing regimens for bleeding prevention. The individual patient with hemophilia B had a history of anaphylaxis at inhibitor development and received on-demand BPA for acute bleeding events. All 7 bleeds consisted of hemarthroses with the knee being the primary site in 57% of the bleeds. Five of the 7 bleeds (71%) received a severe bleeding dose of 210-225 microgram per kilogram (mcg/kg) for the initial rFVIIa-B dose followed by 70-75 mcg/kg for subsequent doses. Final dosing regimens were dependent on available vial sizes. rFVIIa-B resulted in complete resolution of all bleeds (100%) at a median of 4 doses (range 1-8 doses) and a median of 24 hours (range 3-48 hours). There were no failures in bleeding resolution following treatment. No adverse events with infusions were reported including infusion-related reactions, hypersensitivity reactions, thrombosis, or thrombotic microangiopathy. Conclusions: Administration of rFVIIa-B in the real-world setting appears to demonstrate hemostatic efficacy in a cohort of pediatric and adult patients with hemophilia A and B with inhibitors and may serve as an alternative human rFVIIa therapy for the management of acute bleeds in this population. Further post-marketing studies are warranted to expand the indication to younger children (<12 years of age) and to continue to monitor drug efficacy and adverse events in a larger population of patients over time including individuals on non-factor therapies such as emicizumab. Figure 1 Figure 1. Disclosures Batsuli: Bio Product Laboratory: Honoraria; Kedrion: Honoraria. Tran: HEMA Biologics: Honoraria. Young: Apcintex, BioMarin, Genentech/Roche, Grifols, Novo Nordisk, Pfizer, Rani, Sanofi Genzyme, Spark, Takeda, and UniQure: Consultancy; Genentech/Roche, Grifols, and Takeda: Research Funding. Sidonio: Guardian Therapeutics: Consultancy; Octapharma: Consultancy, Research Funding; Catalyst: Consultancy; Pfizer: Consultancy; Takeda: Consultancy, Research Funding; Biomarin: Consultancy; Novo Nordisk: Consultancy; Bayer: Consultancy; Genentech: Consultancy, Research Funding.

Perioperative Management of Subdural Hemorrhage (SDH) Trepanation Decompression with Hemophilia A

<p>Hemophilia is a serious inherited blood disease, transmitted by women, that affects mainly men and lasts for a lifetime. Hemophilia A is the most common form. If any of the factors necessary for blood clotting are absent or insufficient, the clotting mechanism is disturbed, causing insatiable bleeding. The most common cause of death in hemophilia patients is cerebral hemorrhage due to head trauma. In cases of intracranial hemorrhage, surgery should be performed immediately to obtain a better prognosis. A 17-year-old man diagnosed with a 2x4 loss of consciousness due to intracranial subdural hemorrhage (SDH) in the left frontotemporoparietal region and cerebral edema on day 4 accompanied by subfalcine herniation to the right with hemophilia A, planned trepanation decompression for SDH evacuation. The patient received 4000 units of factor VIII injection before surgery. Bleeding during surgery was 1100cc and he received a transfusion of 1940cc blood products until hemodynamically stable. In the postoperative phase, he was admitted to the ICU for 8 days, extubation was performed after the condition improved. In patient with hemophilia, evacuation of bleeding should be performed immediately, but there is a high risk of rebleeding. A recombinant factor VIII substitute should be administered immediately for the treatment of acute bleeding in patients with severe haemophilia A. Anesthetic maintenance should include reducing the risk of hypertension and tachycardia to minimize bleeding.</p>

Red Blood Cell Transfusion in the Emergency Department: An Observational Cross-Sectional Multicenter Study

Background: We aimed to describe red blood cell (RBC) transfusions in the emergency department (ED) with a particular focus on the hemoglobin (Hb) level thresholds that are used in this setting. Methods: This was a cross-sectional study of 12 EDs including all adult patients that received RBC transfusion in January and February 2018. Descriptive statistics were reported. Logistic regression was performed to assess variables that were independently associated with a pre-transfusion Hb level ≥ 8 g/dL. Results: During the study period, 529 patients received RBC transfusion. The median age was 74 (59–85) years. The patients had a history of cancer or hematological disease in 185 (35.2%) cases. Acute bleeding was observed in the ED for 242 (44.7%) patients, among which 145 (59.9%) were gastrointestinal. Anemia was chronic in 191 (40.2%) cases, mostly due to vitamin or iron deficiency or to malignancy with transfusion support. Pre-transfusion Hb level was 6.9 (6.0–7.8) g/dL. The transfusion motive was not notified in the medical chart in 206 (38.9%) cases. In the multivariable logistic regression, variables that were associated with a higher pre-transfusion Hb level (≥8 g/dL) were a history of coronary artery disease (OR: 2.09; 95% CI: 1.29–3.41), the presence of acute bleeding (OR: 2.44; 95% CI: 1.53–3.94), and older age (OR: 1.02/year; 95% CI: 1.01–1.04). Conclusion: RBC transfusion in the ED was an everyday concern and involved patients with heterogeneous medical situations and severity. Pre-transfusion Hb level was rather restrictive. Almost half of transfusions were provided because of acute bleeding which was associated with a higher Hb threshold.

Effects of Proton Pump Inhibitor on Gastroesophageal Varices of Cirrhosis: A Randomized Controlled Trial

BackgroundThe use of proton pump inhibitor (PPI) for gastroesophageal varices in patients with cirrhosis after endoscopic therapy remains controversial. This study aimed to evaluate the effect of PPI on gastroesophageal varices in patients with cirrhosis after endoscopic therapy, including variceal bleeding and adverse events.MethodsBetween May 2017 and June 2019, cirrhotic patients with gastroesophageal varices confirmed by endoscopy were considered for enrollment in this study. Eligible subjects were randomized into two groups: one group received PPI for 14 days and the other group did not undergo PPI treatment. Patients were followed up for 8 weeks.ResultsDuring the follow-up period, three patients (3/53, 5.66%) in the PPI group experienced variceal bleeding on day 9, 16, and 25 after endoscopic therapy, including one patient with primary prophylaxis and two with acute bleeding. In the non-PPI group, three patients (3/56, 5.66%) suffered from variceal bleeding on day 7, 42, and 56 after endoscopic therapy, including two patients with secondary prophylaxis and one with acute bleeding (P>0.99). The rate of adverse events was similar between the two groups (38% vs. 28%, P=0.30). Furthermore, the average hospitalization expense of patients in the PPI group was higher than that of patients in the non-PPI group ($2305 vs. $3096, P<0.001).ConclusionsPPI does not appear to reduce variceal bleeding and adverse events in patients with cirrhosis after endoscopic therapy.Trial registration: This trial was registered with ClinicalTrials.gov (NCT 03175731, 05/06/2017).