Intraoperative Bleeding Management: An Updating Literature Review: Review Article

Background: Intraoperative bleeding remains a major complication during and after surgery, leading to increased morbidity and mortality. Several influences determine the complex causes of bleeding in surgical patients. About 75 to 90% of early intraoperative and postoperative bleeding is due to technical factors. In some cases, however, acquired or congenital coagulopathies can stimulate, if not directly cause, surgical bleeding. Objectives: This paper aims to overview etiology, causes, diagnosis, and updated management of intraoperative bleeding. Methods: The review article ran from July 1, 2021 to October 31, 2021. We searched articles on etiology, causes, and treatments published in English worldwide in the Medline, EBSCO and PubMed databases. No software was used to analyze the data. Team members reviewed the data to determine initial results. Results: All patients scheduled for elective surgery should be screened for possible hemostatic defects using tests, and, if necessary, laboratory tests. Treatment of intraoperative bleeding consists of identifying patients at risk and understanding the effect of surgery on hemostasis. For patients at high risk of bleeding, a pre-operative meeting with a multidisciplinary team (anesthesiologist, surgeon, hematologist, radiologist) can discuss the correct surgical procedure. Conclusion: Technical variables account for 75-90% of initial intraoperative and postoperative bleeding. However, in other cases it is associated with acquired or congenital coagulation disorders. All patients scheduled for elective surgery should be checked for problems with hemostasis. Treatment of intraoperative bleeding involves identifying those at risk and understanding the effect of surgery on hemostasis.

Use of Innovative Technologies in the Treatment of Patients with Severe Concomitant Injury with Liver Damage: Clinical Observation

Liver injury is one of the most common abdominal injuries in patients with severe trauma. A total of 2988 patients with concomitant injuries were treated at the city clinical hospital named after S.S. Yudin during the period from 2010 to 2020, of which 371 (12.4%) were found to have closed abdominal trauma. Damage to the liver was revealed in 124 (33.4%) patients with closed abdominal trauma. The number of discharged patients was 78 (62,9%), lethal outcome — 46 patients (37,1%). The severity of injury according to ISS was (38,1±11,3) points. The development of innovative multimodal approaches, such as endovascular trauma and bleeding management (EVTM), as well as damage control tactics have significantly increased the likelihood of nonoperative treatment for individual patients. A clinical observation is presented that allows to evaluate the effectiveness of innovative technologies in the treatment of patients with severe concomitant trauma with liver damage.

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.

Barriers and facilitators to implementing evidence based bleeding management in Australian Cardiac Surgery Units: a qualitative interview study analysed with the theoretical domains framework and COM-B model

Background Bleeding during cardiac surgery is a common complication that often requires the transfusion of blood products. The combination of bleeding and blood product transfusion incrementally increases adverse outcomes including infection and mortality. Following bleeding management guideline recommendations could assist with minimising risk but adherence is not high, and the cause for lack of adherence is not well understood. This study aimed to identify barriers and facilitators to practicing and implementing evidenced-based intra-operative, bleeding management in Australian cardiac surgery units. Methods We used a qualitative descriptive design to conduct semi-structured interviews with Australian cardiac surgeons, anaesthetists and perfusionists. The Theoretical Domains Framework (TDF) was utilised to guide interviews and thematically analyse the data. Categorised data were then linked with the three key domains of the COM-B model (capability, opportunity, motivation - behaviour) to explore and understand behaviour. Results Seventeen interviews were completed. Nine of the 14 TDF domains emerged as significant. Analysis revealed key themes to improving capability included, standardisation, monitoring, auditing and feedback of data and cross discipline training. Opportunity for change was improved with interpersonal and interdepartmental collaboration through shared goals, and more efficient and supportive processes allowing clinicians to navigate unfamiliar business and financial models of health care. Results suggest as individuals, clinicians had the motivation to make change and healthcare organisations have an obligation and a responsibility to partner with clinicians to support change and improve goal directed best practice. Conclusion Using a theory-based approach it was possible to identify factors which may be positively or negatively influence clinicians ability to implement best practice bleeding management in Australian cardiac surgical units.

Understanding and managing the complex balance between bleeding and thrombosis following cardiopulmonary bypass in paediatric cardiac surgical patients

Bleeding in the perioperative period of congenital heart surgery with cardiopulmonary bypass is associated with increased morbidity and mortality both from the direct effects of haemorrhage as well as the therapies deployed to restore haemostasis. Perioperative bleeding is complex and multifactorial with both patient and procedural contributions. Moreover, neonates and infants are especially at risk. The objective of this review is to summarise the evidence regarding bleeding management in paediatric surgical patients and identify strategies that might facilitate appropriate bleeding management while minimising the risk of thrombosis. We will address the use of standard and point-of-care tests, and the role of contemporary coagulation factors and other novel drugs.

Emergency Cardiac Surgery in Patients on Oral Anticoagulants and Antiplatelet Medications

Emergency surgery, blood transfusion, and reoperation for bleeding have been associated with increased operative morbidity and mortality. The recent increased use of direct oral anticoagulants and antiplatelet medications have made the above more challenging. In addition, cardiopulmonary bypass (CPB) with its associated hemodilution, fibrinolysis and platelet consumption may exacerbate the pre-existing coagulopathy and increase the risk of bleeding. Management decisions are typically made on a case-by-case basis. Surgery is delayed when possible and less invasive percutaneous options should be considered if feasible. Attention is paid to exercising meticulous techniques, avoiding excessive hypothermia and treating coexisting issues such as sepsis. Ensuring a dry operative field upon entry by correcting the coagulopathy with reversal agents is offset by the concern of potentially hindering efforts to anticoagulate the patient (heparin resistance) in preparation for CPB, in addition to possibly increasing the risk of thromboembolism. Proper knowledge of the anticoagulants, their reversal agents, and the usefulness of laboratory testing are all essential. Platelet transfusion remains mainstay for antiplatelet medications. Four-factor prothrombin complex concentrate is considered in patients on oral anticoagulants if CPB needs to be instituted quickly. Specific reversal agents such as idarucizumab and andexanet alfa can be considered if significant tissue dissection is anticipated such as redo sternotomy, but are costly and may lead to heparin resistance and anticoagulant rebound.