ADE Fibrinogen/RBC Ratio on Mortality and Outcome in Massive Transfusion Patients

Study Overview
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Brief Summary
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The primary objective of our study is to determine the impact of the ratio of total amount of fibrinogen transfused over 24 hours to erythrocyte suspension (ADE Fibrinogen/ES) on 30-day death from any cause OR death from bleeding OR total ES transfusion OR quality of life.

Detailed Description
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Massive transfusion, defined as the transfusion of total body blood volume (10 units of erythrocyte suspension) or more within 24 hours, remains one of the greatest challenges for the anesthetist. Despite all the medical advances, in cardiac surgery, obstetric surgery, trauma-orthopedic surgery, major gastrointestinal-genitor-urinary system surgeries, which are among the major bleeding surgeries, massive hemorrhage continues to be an important mortality and morbidity factor. In addition to major surgeries with known expected bleeding, massive transfusion requirement may arise with any undesirable intraoperative event. While the process is easier to manage with proper preparation and an organized procedure in expected bleeding, a chaotic response may be encountered in unexpected situations. Special protocols for each division have been developed by clinicians to manage this critical process, and work continues on these protocols to improve the outcome. Massive bleeding management mainly focuses on transfusion and fluid resuscitation. Regardless of the situation requiring massive transfusion, the goals of treatment in massive bleeding are to maintain organ perfusion pressure and oxygen delivery, immediately stop bleeding and coagulopathy. While these goals can be achieved through resuscitation with blood products and surgical intervention, the triad of hypothermia, acidosis, and coagulopathy that occurs with the process contributes to increased morbidity and mortality in such scenarios. The literature on major bleeding from trauma has highlighted some issues contributed to improved clinical outcomes such as, damage-controlled resuscitation, including timely initiation of transfusion, early use of clotting factors, minimizing the use of crystalloids. The landmark PROPPR study found that in the resuscitation of trauma patients, a 1:1:1 ratio of FFP:platelet:RBC transfusion during massive bleeding resulted in hemostasis in a greater number of patients (86% versus 78%) compared to a 1:1:2 ratio, additionally, they found fewer deaths from bleeding within 24 hours (14.6% versus 9.2%). However, no significant difference was found in 24-hour or 30-day overall mortality. In a systematic review evaluating retrospective data on transfusions for obstetric bleeding, it was shown that the amount of FFP administered was greater than the amount of RBC. Since the mortality rate from massive obstetric hemorrhage is lower than that of traumatic hemorrhage, it is difficult to prospectively evaluate the effects of massive transfusion. This review recommends a FFP/RBC ratio of ≥1, with the results of all retrospective studies described on transfusions for obstetric hemorrhage. Studies in cardiac surgery also suggest that higher rates of FFP/RBC transfusion are associated with better outcomes in patients with massive bleeding. In general, the high ratio of transfused FFP to RBC in bleeding surgeries requiring massive transfusion has been associated with positive results. FFP contains all coagulation factors and fibrinogen, as well as restoring the volume deficit that occurs with major bleeding, which reduces the crystalloid requirement and prevents extra dilution of coagulation factors. Fibrinogen is the clotting factor whose level drops the fastest during bleeding. Fibrinogen is a unique coagulation building block that plays a role in both primary and secondary hemostasis. Based on the results of the RETIC trial, the effectiveness of fibrinogen supplementation in limiting blood loss appears to be strongly dependent on timing of fibrinogen administration and increasing levels above 200 mg·dL-1. The 5th Edition of the European Guidelines for the Management of Major Posttraumatic Hemorrhage and Coagulopathy recommends early and repeated monitoring of fibrinogen concentrations and/or polymerization and rapid correction of deficiencies. Accordingly, 3-4 g of fibrinogen concentrate or 15-20 units of cryoprecipitate is recommended as an initial dose in massive bleeding. While RETIC stands out as a randomized controlled prospective study on the role of fibrinogen in massive transfusion in trauma patients, there are few cardiac and transplantation surgery studies in various types of research. Regardless of the cause, early restoration of fibrinogen levels in case of massive bleeding reduces transfusion requirement by preventing ongoing bleeding. Ideally, fibrinogen concentrate and/or cryoprecipitate are used in fibrinogen replacement, and FFP is used as a weaker fibrinogen source. During massive transfusion, repeated doses of FFP/cryoprecipitate/fibrinogen concentrate are used. All of these blood products have different amounts of fibrinogen content. In many previous studies, the formula for improving the results was investigated by looking at transfusion rates such as FFP/RBC, RBC/platelet, FFP/RBC/Platelet. In the light of this information, our hypothesis is that mortality can be reduced with a high rate of total fibrinogen transfusion from various sources. The primary aim of our study is to determine the effects of the ratio of total fibrinogen transfused over 24 hours amount to erythrocyte suspension (ACE Fibrinogen/RBC) on 30-day death from any cause OR death from bleeding OR total ES transfusion OR quality of life.

Official Title
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The Impact of ADE Fibrinogen/RBC Ratio on Mortality and Outcome in Massive Transfusion Patients: ADEFES TRIAL

Conditions
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Massive Transfusion

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 Surgical patients who received ≥ 4 U RBC transfusions within 24 hours 5 U RBC transfusion within 4 h 4 U RBC transfusion within 1 h Bleeding in excess of 1.5 mL/kg/min, over 20 min Elective or emergency surgical procedures with major bleeding. Major bleeding surgeries; cardiovascular surgery, obstetric surgery, orthopedics/trauma surgery and major GIS-GUS surgeries Informed Consent Exclusion Criteria: Death before massive transfusion Death during massive transfusion Patients whose perioperative bleeding and transfusion data cannot be accessed in detail Patients with missing data or non-compliance with study protocol

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality within the first 30 days of follow-up. |  | 30-day survival after massive transfusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival |  | 24-hour mortality | 
| Survival |  | 3-month mortality | 
| Mortality predictive biomarkers | Mortality predictive biomarkers | 3-month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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massive transfusion, fibrinogen, fresh frozen plasma