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.

Injectable Human Hair Keratin–Fibrinogen Hydrogels for Engineering 3D Microenvironments to Accelerate Oral Tissue Regeneration

Traumatic injury of the oral cavity is atypical and often accompanied by uncontrolled bleeding and inflammation. Injectable hydrogels have been considered to be promising candidates for the treatment of oral injuries because of their simple formulation, minimally invasive application technique, and site-specific delivery. Fibrinogen-based hydrogels have been widely explored as effective materials for wound healing in tissue engineering due to their uniqueness. Recently, an injectable foam has taken the spotlight. However, the fibrin component of this biomaterial is relatively stiff. To address these challenges, we created keratin-conjugated fibrinogen (KRT-FIB). This study aimed to develop a novel keratin biomaterial and assess cell–biomaterial interactions. Consequently, a novel injectable KRT-FIB hydrogel was optimized through rheological measurements, and its injection performance, swelling behavior, and surface morphology were investigated. We observed an excellent cell viability, proliferation, and migration/cell–cell interaction, indicating that the novel KRT-FIB-injectable hydrogel is a promising platform for oral tissue regeneration with a high clinical applicability.

Reversal Activity and Toxicity of Heparin-Binding Copolymer after Subcutaneous Administration of Enoxaparin in Mice

Uncontrolled bleeding after enoxaparin (ENX) is rare but may be life-threatening. The only registered antidote for ENX, protamine sulfate (PS), has 60% efficacy and can cause severe adverse side effects. We developed a diblock copolymer, heparin-binding copolymer (HBC), that reverses intravenously administered heparins. Here, we focused on the HBC inhibitory activity against subcutaneously administered ENX in healthy mice. BALB/c mice were subcutaneously injected with ENX at the dose of 5 mg/kg. After 110 min, vehicle, HBC (6.25 and 12.5 mg/kg), or PS (5 and 10 mg/kg) were administered into the tail vein. The blood was collected after 3, 10, 60, 120, 360, and 600 min after vehicle, HBC, or PS administration. The activities of antifactors Xa and IIa and biochemical parameters were measured. The main organs were collected for histological analysis. HBC at the lower dose reversed the effect of ENX on antifactor Xa activity for 10 min after antidote administration, whereas at the higher dose, HBC reversed the effect on antifactor Xa activity throughout the course of the experiment. Both doses of HBC completely reversed the effect of ENX on antifactor IIa activity. PS did not reverse antifactor Xa activity and partially reversed antifactor IIa activity. HBC modulated biochemical parameters. Histopathological analysis showed changes in the liver, lungs, and spleen of mice treated with HBC and in the lungs and heart of mice treated with PS. HBC administered in an appropriate dose might be an efficient substitute for PS to reverse significantly increased anticoagulant activity that may be connected with major bleeding in patients receiving ENX subcutaneously.

Features of the infusion therapy at the prehospital stage with the ongoing bleeding

The article covers the principles of holding the infusion therapy at the prehospital stage with the ongoing uncontrolled bleeding. The scientific work shows the effectiveness of isoosmolar crystalloid solutions in conditions of low capillary pressure, which is typical for blood loss. The article shows that the concept of an acceptable hypotension is the most optimal approach to the infusion therapy if the ongoing bleeding is suspected in peacetime as well as in combat conditions. Recommendations are given for ensuring and maintaining venous access during short, long and delayed evacuation of victims with the suspected ongoing bleeding.

Laparoscopic pectopexy: the learning curve and comparison with laparoscopic sacrocolpopexy

Introduction and hypothesis In addition to laparoscopic sacrocolpopexy (LS), laparoscopic pectopexy (LP) is a novel surgical method for correcting apical prolapse. The descended cervix or vaginal vault is suspended with a synthetic mesh by fixing the bilateral mesh ends to the pectineal ligaments. This study was aimed at developing a learning curve for LP and to compare it with results with LS. Methods We started laparoscopic/robotic pectopexy in our department in August 2019. This retrospective study included the initial 18 consecutive women with apical prolapse receiving LP and another group undergoing LS (21 cases) performed by the same surgeon. The medical and video records were reviewed. Results The age was older in the LP group than in the LS group (65.2 vs 53.1 years). The operation time of LP group was significantly shorter than that of the LS group (182.9 ± 27.2 vs 256.2 ± 45.5 min, p < 0.001). The turning point of the LP learning curve was observed at the 12th case. No major complications such as bladder, ureteral, bowel injury or uncontrolled bleeding occurred in either group. Postoperative low back pain and defecation symptoms occurred exclusively in the LS group. During the follow-up period (mean 7.2 months in LP, 16.2 months in LS), none of the cases had recurrent apical prolapse. Conclusions Laparoscopic pectopexy is a feasible surgical method for apical prolapse, with a shorter operation time and less postoperative discomfort than LS. LP may overcome the steep learning curve of LS because the surgical field of LP is limited to the anterior pelvis and avoids encountering the critical organs.

Uncontrolled bleeding during tooth extraction from an undiagnosed arteriovenous malformation

Arteriovenous malformations (AVMs) are rare congenital disorders of vascular morphogenesis. These lesions are characterised by high vascular flow with risk of severe bleeding from accidental trauma or surgical manipulation. Although infrequent, potentially life-threatening and fatal oral bleeding has been reported during extraction of tooth associated with AVM. This paper presents a case of uncontrolled bleeding in an adult female patient undergoing mandibular anterior tooth extraction. The bleeding was related to undiagnosed soft tissue AVM in gingivobuccal space. Management of the case with review of previously reported similar cases is presented.

Uncrossmatched Blood Transfusion for Resuscitation Patients at the Emergency Department

BACKGROUND: Patients with uncontrolled blood loss often require immediate blood transfusion after the bleeding is stopped. If it is an emergency situation, blood that has not been tested for compatibility (uncrossmatched red blood cell [URBC] products) can be used. However, no studies have been conducted to evaluate the effectiveness of this protocol. AIM: The aim of the study is to evaluate the effectiveness of URBC transfusion in Srinagarind Hospital’s emergency department (ED). METHODS: This was a cross-sectional study that reviewed the medical records of ninty Thai patients over 18 years of age who received at least one unit of blood through URBC transfusion in the Srinagarind Hospital ED from September 2016 to August 2018. RESULTS: The average age of the patients was 47.23 ± 18.2 years, and 73.3% were male. A total of 149 units of URBC were provided, with 54.44% of recipients being trauma patients and 27.78% being gastrointestinal bleeding patients. The 24-h and in-hospital mortality rates were 58.89 and 72.22%, respectively. There were no cases of acute blood transfusion complications or inappropriate URBC transfusion. CONCLUSIONS: The transfusion of URBC necessary in patients with uncontrolled bleeding. No complications were found due to acute blood transfusion.

Simplified treatment algorithm for the management of trauma-induced hemorrhage without viscoelastic testing

Uncontrolled bleeding after major trauma remains a significant cause of death, with up to a third of trauma patients presenting with signs of coagulopathy at hospital admission. Rapid correction of coagulopathy is therefore vital to improve mortality rates and patient outcomes in this population. Early and repeated monitoring of coagulation parameters followed by clear protocols to correct hemostasis is the recommended standard of care for bleeding trauma patients. However, although a number of treatment algorithms are available, these are frequently complex and can rely on the use of viscoelastic testing, which is not available in all treatment centers. We therefore set out to develop a concise and pragmatic algorithm to guide treatment of bleeding trauma patients without the use of point-of-care viscoelastic testing. The algorithm we present here is based on published guidelines and research, includes recommendations regarding treatment and dosing, and is simple and clear enough for even an inexperienced physician to follow. In this way, we have demonstrated that treatment protocols can be developed and adapted to the resources available, to offer clear and relevant guidance to the entire trauma team.