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      Trauma-induced coagulopathy and critical bleeding: the role of plasma and platelet transfusion.

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          Abstract

          Hemorrhage is responsible for 30 to 40% of all trauma-related mortality. Among adult trauma patients, 94% of hemorrhage-related deaths occur within 24 h and approximately 60% of these deaths within 3 h of hospital admission. Therefore, appropriate initial fluid resuscitation for bleeding is crucial to avoid preventable trauma-related death. In particular, the resuscitation strategy must be designed to complement prompt correction of anemia, coagulopathies, and thrombocytopenia. Conventional damage control resuscitation (DCR) of patients with severe trauma and massive hemorrhage is usually begun with rapid infusion of 1000 to 2000 mL of crystalloid fluids with subsequent transfusion of type O or uncross-matched red blood cells (RBCs) without plasma such as fresh frozen plasma (FFP) or platelets (PLTs). However, this DCR technique often leads to several adverse events such as abdominal compartment syndrome, acute respiratory distress syndrome, multiple organ failure, and dilutional coagulopathy. Simultaneous transfusion of FFP and PLTs along with the first units of RBCs while minimizing crystalloid infusion was recently recommended as a renewed DCR strategy. This aggressive RBC transfusion with FFP and PLTs is not only essential for the correction of coagulopathies and thrombocytopenia but also has the potential to ensure a good outcome in trauma patients. Additionally, it is important to maintain the resuscitation ratios of FFP/RBC and PLT/RBC. Most recently, DCR has been advocated for rapid hemorrhage control through early administration of a mixture of FFP, PLTs, and RBCs in a balanced ratio of 1:1:1.

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          Most cited references50

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          Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial.

          Severely injured patients experiencing hemorrhagic shock often require massive transfusion. Earlier transfusion with higher blood product ratios (plasma, platelets, and red blood cells), defined as damage control resuscitation, has been associated with improved outcomes; however, there have been no large multicenter clinical trials. To determine the effectiveness and safety of transfusing patients with severe trauma and major bleeding using plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio. Pragmatic, phase 3, multisite, randomized clinical trial of 680 severely injured patients who arrived at 1 of 12 level I trauma centers in North America directly from the scene and were predicted to require massive transfusion between August 2012 and December 2013. Blood product ratios of 1:1:1 (338 patients) vs 1:1:2 (342 patients) during active resuscitation in addition to all local standard-of-care interventions (uncontrolled). Primary outcomes were 24-hour and 30-day all-cause mortality. Prespecified ancillary outcomes included time to hemostasis, blood product volumes transfused, complications, incidence of surgical procedures, and functional status. No significant differences were detected in mortality at 24 hours (12.7% in 1:1:1 group vs 17.0% in 1:1:2 group; difference, -4.2% [95% CI, -9.6% to 1.1%]; P = .12) or at 30 days (22.4% vs 26.1%, respectively; difference, -3.7% [95% CI, -10.2% to 2.7%]; P = .26). Exsanguination, which was the predominant cause of death within the first 24 hours, was significantly decreased in the 1:1:1 group (9.2% vs 14.6% in 1:1:2 group; difference, -5.4% [95% CI, -10.4% to -0.5%]; P = .03). More patients in the 1:1:1 group achieved hemostasis than in the 1:1:2 group (86% vs 78%, respectively; P = .006). Despite the 1:1:1 group receiving more plasma (median of 7 U vs 5 U, P < .001) and platelets (12 U vs 6 U, P < .001) and similar amounts of red blood cells (9 U) over the first 24 hours, no differences between the 2 groups were found for the 23 prespecified complications, including acute respiratory distress syndrome, multiple organ failure, venous thromboembolism, sepsis, and transfusion-related complications. Among patients with severe trauma and major bleeding, early administration of plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio did not result in significant differences in mortality at 24 hours or at 30 days. However, more patients in the 1:1:1 group achieved hemostasis and fewer experienced death due to exsanguination by 24 hours. Even though there was an increased use of plasma and platelets transfused in the 1:1:1 group, no other safety differences were identified between the 2 groups. clinicaltrials.gov Identifier: NCT01545232.
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            The prospective, observational, multicenter, major trauma transfusion (PROMMTT) study: comparative effectiveness of a time-varying treatment with competing risks.

            To relate in-hospital mortality to early transfusion of plasma and/or platelets and to time-varying plasma:red blood cell (RBC) and platelet:RBC ratios. Prospective cohort study documenting the timing of transfusions during active resuscitation and patient outcomes. Data were analyzed using time-dependent proportional hazards models. Ten US level I trauma centers. Adult trauma patients surviving for 30 minutes after admission who received a transfusion of at least 1 unit of RBCs within 6 hours of admission (n = 1245, the original study group) and at least 3 total units (of RBCs, plasma, or platelets) within 24 hours (n = 905, the analysis group). In-hospital mortality. Plasma:RBC and platelet:RBC ratios were not constant during the first 24 hours (P < .001 for both). In a multivariable time-dependent Cox model, increased ratios of plasma:RBCs (adjusted hazard ratio = 0.31; 95% CI, 0.16-0.58) and platelets:RBCs (adjusted hazard ratio = 0.55; 95% CI, 0.31-0.98) were independently associated with decreased 6-hour mortality, when hemorrhagic death predominated. In the first 6 hours, patients with ratios less than 1:2 were 3 to 4 times more likely to die than patients with ratios of 1:1 or higher. After 24 hours, plasma and platelet ratios were unassociated with mortality, when competing risks from nonhemorrhagic causes prevailed. Higher plasma and platelet ratios early in resuscitation were associated with decreased mortality in patients who received transfusions of at least 3 units of blood products during the first 24 hours after admission. Among survivors at 24 hours, the subsequent risk of death by day 30 was not associated with plasma or platelet ratios.
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              Early coagulopathy predicts mortality in trauma.

              Coagulopathy and hemorrhage are known contributors to trauma mortality; however, the actual relationship of prothrombin time (PT) and partial thromboplastin time (PTT) to mortality is unknown. Our objective was to measure the predictive value of the initial coagulopathy profile for trauma-related mortality. We reviewed prospectively collected data on trauma patients presenting to a Level I trauma center. A logistic regression analysis was performed of PT, PTT, platelet count, and confounders to determine whether coagulopathy is a predictor of all-cause mortality. From a trauma registry cohort of 20103 patients, 14397 had complete disposition data for initial analysis and 7638 had complete data for all variables in the final analysis. The total cohort was 76.2% male, the mean age was 38 years (range, 1-108 years), and the median Injury Severity Score was 9. There were 1276 deaths (all-cause mortality, 8.9%). The prevalence of coagulopathy early in the postinjury period was substantial, with 28% of patients having an abnormal PT (2994 of 10790) and 8% of patients having an abnormal PTT (826 of 10453) on arrival at the trauma bay. In patients with disposition data and a normal PT, 489 of 7796 died, as compared with 579 of 2994 with an abnormal PT (6.3% vs. 19.3%; chi2 = 414.1, p < 0.001). Univariate analysis generated an odds ratio of 3.6 (95% confidence interval [CI], 3.15-4.08; p < 0.0001) for death with abnormal PT and 7.81 (95% CI, 6.65-9.17; p < 0.001) for deaths with an abnormal PTT. The PT and PTT remained independent predictors of mortality in a multiple regression model, whereas platelet count did not. The model also included the independent risk factors age, Injury Severity Score, scene and trauma-bay blood pressure, hematocrit, base deficit, and head injury. The model generated an adjusted odds ratio of 1.35 for PT (95% CI, 1.11-1.68; p < 0.001) and 4.26 for PTT (95% CI, 3.23-5.63; p < 0.001). The incidence of coagulation abnormalities, early after trauma, is high and they are independent predictors of mortality even in the presence of other risk factors. An initial abnormal PT increases the adjusted odds of dying by 35% and an initial abnormal PTT increases the adjusted odds of dying by 326%.
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                Author and article information

                Journal
                J Intensive Care
                Journal of intensive care
                Springer Science and Business Media LLC
                2052-0492
                2052-0492
                Jan 20 2017
                : 5
                : 1
                Affiliations
                [1 ] Department of Emergency and Critical Care Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan. ishikurah@fukuoka-u.ac.jp.
                [2 ] Department of Emergency and Critical Care Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
                Article
                10.1186/s40560-016-0203-y
                10.1186/s40560-016-0203-y
                8600862
                34798700
                d759e56c-5ea5-481a-81fa-e5de5b103b27
                History

                Damage control resuscitation,Acute traumatic coagulopathy,Acute coagulopathy of trauma shock,Trauma-induced coagulopathy,Trauma,Plasma,FFP,Fresh frozen plasma,Platelet,Transfusion

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