Hemostatic resuscitation with plasma and platelets in trauma

Balanced blood component administration during massive transfusion is standard of care. Most literature focuses on the impact of red blood cell (RBC)/fresh frozen plasma (FFP) ratio, while the value of balanced RBC:platelet (PLT) administration is less established. The aim of this study was to evaluate and quantify the independent impact of RBC:PLT on 24-hour mortality in trauma patients receiving massive transfusion. Using the 2013 to 2018 American College of Surgeons Trauma Quality Improvement Program database, adult patients who received massive transfusion (≥10 U of RBC/24 hours) and ≥1 U of RBC, FFP, and PLT within 4 hours of arrival were retrospectively included. To mitigate survival bias, only patients with consistent RBC:PLT and RBC:FFP ratios between 4 and 24 hours were analyzed. Balanced FFP or PLT transfusions were defined as having RBC:PLT and RBC:FFP of ≤2, respectively. Multivariable logistic regression was used to compare the independent relationship between RBC:FFP, RBC:PLT, balanced transfusion, and 24-hour mortality. A total of 9,215 massive transfusion patients were included. The number of patients who received transfusion with RBC:PLT >2 (1,942 [21.1%]) was significantly higher than those with RBC:FFP >2 (1,160 [12.6%]) (p < 0.001). Compared with an RBC:PLT ratio of 1:1, a gradual and consistent risk increase was observed for 24-hour mortality as the RBC:PLT ratio increased (p < 0.001). Patients with both FFP and PLT balanced transfusion had the lowest adjusted risk for 24-hour mortality. Mortality increased as resuscitation became more unbalanced, with higher odds of death for unbalanced PLT (odds ratio, 2.48 [2.18-2.83]) than unbalanced FFP (odds ratio, 1.66 [1.37-1.98]), while patients who received both FFP and PLT unbalanced transfusion had the highest risk of 24-hour mortality (odds ratio, 3.41 [2.74-4.24]). Trauma patients receiving massive transfusion significantly more often have unbalanced PLT rather than unbalanced FFP transfusion. The impact of unbalanced PLT transfusion on 24-hour mortality is independent and potentially more pronounced than unbalanced FFP transfusion, warranting serious system-level efforts for improvement. Therapeutic/Care Management; Level IV.

Case Scenario: Management of Trauma-induced Coagulopathy in a Severe Blunt Trauma Patient

Continued hemorrhage remains a major contributor of mortality in massively transfused patients and controversy regarding the optimal management exists. Recent studies indicate a possible survival benefit in patients receiving a higher ratio of plasma and platelets (PLTs) to red blood cells (RBCs) than what is recommended in current transfusion guidelines. English databases were searched for reports of patients receiving massive transfusion that tested the effects of administration of plasma and/or PLTs in relation to RBCs on survival from January 1990 to March 2009. Fourteen retrospective studies involving 4594 patients were identified. Six tested the effect on survival in relation to fresh-frozen plasma (FFP)-to-RBC ratio, and five investigated FFP- and PLT-to-RBC ratios. Two studies evaluated implementation of massive transfusion protocols with preemptive FFP and PLT administration; one study based transfusion therapy on the result of the thrombelastograph (TEG) analysis versus historic controls. All studies reviewed demonstrate a survival benefit for patients who receive more FFP and PLT as part of the hemostatic resuscitation. When TEG was used to guide transfusion therapy an increase in FFP and PLT was also seen when compared to historic controls and this was associated with improved survival. High FFP- and PLT-to-RBC ratios seem to improve survival in patients with massive bleeding. Randomized studies evaluating TEG-guided transfusion therapy versus fixed ratios of plasma and PLTs to RBCs in massively bleeding patients is highly warranted.

Hemostatic resuscitation has been shown to be beneficial for patients with trauma, but there is little evidence that it is equally beneficial for bleeding patients without trauma. The practice of a high transfusion ratio of fresh frozen plasma (FFP) to red blood cells (RBCs) has spread to other surgical and medical fields. To identify whether ratio-based resuscitation in patients without trauma is associated with improved survival. This study is a retrospective review of all massive transfusions provided in an urban academic hospital from January 1, 2009, through December 31, 2012. Massive transfusion was defined as the transfusion of at least 10 U of RBCs in the first 24 hours after a patient's admission to the operating room, emergency department, or intensive care unit. All patients who received massive transfusions within the study period and survived more than 30 minutes after hospital arrival were counted (n=865). Patients were grouped into those with trauma and those without trauma. Sources of data included the Research Patient Data Registry, patients' medical records, and blood bank records. All data collection occurred between April 26, 2013, and April 26, 2015. Data analysis took place from April 27, 2015, and June 22, 2016. Examination of FFP:RBC transfusion ratios for patients without trauma. There were 865 massive transfusion events that occurred within 4 years, transfusing 16 569 U of RBCs, 13 933 U of FFP, 5228 U of cryoprecipitate, and 22 635 U of platelets. Most of these transfusions were received by patients without trauma (767 [88.7%]), by men (582 [67.3%]), and for intraoperative bleeding (544 [62.9%]). The FFP:RBC ratios of survivors and nonsurvivors were nearly identical: the ratio for survivors was 1:1.5 (interquartile range [IQR], 1:1.1-1:2.2) and for nonsurvivors was 1:1.4 (IQR, 1:1.1-1:1.9; P = .43). Among the 767 patients without trauma, there was no difference in the adjusted odds ratio (aOR) for 30-day mortality when comparing the high FFP:RBC ratio vs the low FFP:RBC ratio subgroups (aOR, 1.10; 95% CI, 0.72-1.70; P = .65). In vascular surgery, the aOR for death favored the high FFP:RBC ratio subgroup (aOR, 0.16; 95% CI, 0.03-0.79; P = .02). However, in general surgery and medicine, the aOR for death favored the low FFP:RBC ratio subgroup; general surgery: aOR, 4.27 (95% CI, 1.28-14.22; P = .02); medicine: aOR, 8.48 (95% CI, 1.50-47.75; P = .02). High FFP:RBC transfusion ratios are applied mostly to patients without trauma, who account for nearly 90% of all massive transfusion events. Thirty-day survival was not significantly different in patients who received a high FFP:RBC ratio compared with those who received a low ratio.

Administration of high transfusion ratios in patients not requiring massive transfusion might be harmful. We aimed to determine the effect of high ratios of fresh frozen plasma (FFP) and platelets (PLT) to packed red blood cells (PRBC) in nonmassively transfused patients. Records of 1,788 transfused trauma patients who received <10 units of PRBC in 24 hours at 23 United States Level I trauma centers were reviewed. The relationship between ratio category (low and high) and in-hospital mortality was assessed with propensity-adjusted multivariate proportional hazards models. At baseline, patients transfused with a high FFP:PRBC ratio were younger, had a lower Glasgow Coma Scale score, and a higher Injury Severity Score. Those receiving a high PLT:PRBC ratio were older. The risk of in-hospital mortality did not vary significantly with FFP:PRBC ratio category. Intensive care unit (ICU)-free days, hospital-free days, and ventilator-free days did not vary significantly with FFP:PRBC ratio category. ICU-free days and ventilator-free days were significantly decreased among patients in the high (≥1:1) PLT:PRBC category, and hospital-free days did not vary significantly with PLT:PRBC ratio category. The analysis was repeated using 1:2 as the cutoff for high and low ratios. Using this cutoff, there was still no difference in mortality with either FFP:PRBC ratios or platelet:PRBC ratios. However, patients receiving a >1:2 ratio of FFP:PRBCs or a >1:2 ratio PLT:PRBCs had significantly decreased ICU-free days and ventilator-free days. FFP:PRBC and PLT:PRBC ratios were not associated with in-hospital mortality. Depending on the threshold analyzed, a high ratio of FFP:PRBC and PLT:PRBC transfusion was associated with fewer ICU-free days and fewer ventilator-free days, suggesting that the damage control infusion of FFP and PLT may cause increased morbidity in nonmassively transfused patients and should be rapidly terminated when it becomes clear that a massive transfusion will not be required.

Objective To evaluate the prognostic effect of different ratios of fresh frozen plasma (FFP) to packed red blood cells (PRBC) in massively transfused trauma patients. Methods A retrospective cohort study was conducted for 210 trauma patients who received more than 10 units of PRBC during the initial 24 hours from January 2007 to June 2015. The patients were divided into four groups: Group A(PRBC ∶FFP≤1, n=41), Group B (1 2, n=76). At 24 hours after admission, blood transfusion amount, blood transfusion ratios, post-transfusion adverse reactions (allergy, non-hemolytic febrile transfusion reaction, hemolysis, congestive heart failure, pulmonary edema, etc) and coagulation changes [hemoglobin (Hb), platelet count (PC), prothrombin time(PT), activated partial thromboplastin time(APTT), international normalized ratio (INR), etc] were compared among groups. Prognostic markers including sequential organ failure assessment(SOFA), hospital stay, ICU stay, 30-day mortality and causes of death were also evaluated. Results Use of PRBC was decreased significantly in Group A than in other groups (P 0.05). The coagulation indices (PT, APTT and INR) in Groups A and B were significantly decreased compared to Group D after transfusion (P 0.05). Group D was associated with higher SOFA and higher 30-day mortality than other groups(P 0.05). Meanwhile, ratio of patients died of massive hemorrhage in Group D was also higher than other groups (P<0.01). Kaplan-Meier survival analysis showed the survival interval was the shortest in Group D, while the longest in Group B and C. Conclusions Modest transfusion ratios(1. 5<PRBC ∶FFP≤2)within 24 hours can substantially improve outcomes in trauma patients. Aggressive ratios may improve coagulation indices and reduce use of PRBC, with no more benefit to the outcomes. Key words: Blood component transfusion; Wounds and injuries; Prognosis

Fibrinogen concentrate for management of bleeding

Intraoperative blood product resuscitation and mortality in ruptured abdominal aortic aneurysm

A high ratio of plasma and platelets to packed red blood cells in the first 6 hours of massive transfusion improves outcomes in a large multicenter study

Cardiac surgery is the most common setting for massive transfusion in medically advanced countries. Studies of massive transfusion after injury suggest that the ratios of administered plasma and platelets (PLT) to red blood cells (RBCs) affect mortality. Data from the Red Cell Storage Duration Study (RECESS), a large randomized trial of the effect of RBC storage duration in patients undergoing complex cardiac surgery, were analyzed retrospectively to investigate the association between blood component ratios used in massively transfused patients and subsequent clinical outcomes. Massive transfusion was defined as those who had ≥6 RBC units or ≥8 total blood components. For plasma, high ratio was defined as ≥1 plasma unit:1 RBC unit. For PLT transfusion, high ratio was defined as ≥0.2 PLT doses:1 RBC unit; PLT dose was defined as 1 apheresis PLT or 5 whole blood PLT equivalents. The clinical outcomes analyzed were mortality and the change in the Multiple Organ Dysfunction Score (ΔMODS) comparing the preoperative score with the highest composite score through the earliest of death, discharge, or day 7. Outcomes were compared between patients transfused with high and low ratios. Linear and Cox regression were used to explore relationships between predictors and continuous outcomes and time to event outcomes. A total of 324 subjects met the definition of massive transfusion. In those receiving high plasma:RBC ratio, the mean (SE) 7- and 28-day ΔMODS was 1.24 (0.45) and 1.26 (0.56) points lower, (P = .007 and P = .024), respectively, than in patients receiving lower ratios. In patients receiving high PLT:RBC ratio, the mean (SE) 7- and 28-day ΔMODS were 1.55 (0.53) and 1.49 (0.65) points lower (P = .004 and P = .022), respectively. Subjects who received low-ratio plasma:RBC transfusion had excess 7-day mortality compared with those who received high ratio (7.2% vs 1.7%, respectively, P = .0318), which remained significant at 28 days (P = .035). The ratio of PLT:RBCs was not associated with differences in mortality. This analysis found that in complex cardiac surgery patients who received massive transfusion, there was an association between the composition of blood products used and clinical outcomes. Specifically, there was less organ dysfunction in those who received high-ratio transfusions (plasma:RBCs and PLT:RBCs), and lower mortality in those who received high-ratio plasma:RBC transfusions.

Current trauma resuscitation guidelines recommend giving an initial crystalloid bolus as first line for resuscitation. Recent studies have shown a survival benefit for trauma patients resuscitated with high ratios of fresh frozen plasma (FFP) to packed red blood cells (PRBC). Our aim was to determine whether the volume of crystalloid given during resuscitation correlated with differences in morbidity or mortality based on the ratio of FFP:PRBC given. This was a retrospective review of 2,473 transfused trauma patients at 23 Level I trauma centers from July 2005 to October 2007. Patients were separated based on the ratios of FFP:PRBC they received (<1:4, 1:4-1:1, and >1:1) and then analyzed for morbidity and mortality based on whether or not they received at least 1 L crystalloid for each unit of PRBC. Outcomes analyzed were 6-hour, 24-hour, and 30-day survival as well as intensive care unit (ICU)-free days, ventilator-free days, and hospital-free days. Massive transfusion patients who received <1:4 ratios of FFP:PRBC had significantly improved 6-hour, 24-hour, and 30-day mortality and significantly more ventilator-free days if they received at least 1 L of crystalloid for each unit of PRBC. Nonmassive transfusion patients who received <1:4 ratios of FFP:PRBC had significantly improved 6-hour, 24-hour, and 30-day mortality and significantly more ICU-free days, ventilator-free days, and hospital-free days if they received at least 1 L crystalloid for each unit of PRBC. In both massive and nonmassive transfusion groups, the survival benefit and morbidity benefit was progressively less for the 1:4 to 1:1 FFP:PRBC groups and >1:1 FFP:PRBC groups. If high ratios of FFP:PRBC are unable to be given to trauma patients, resuscitation with at least 1 L of crystalloid per unit of PRBC is associated with improved overall mortality.

We use massive transfusion in various clinical conditions and it is associated with high mortality. Although some massive transfusion protocols improve patient outcomes, the clinical circumstances requiring it are not well defined. MATRA-A is a multicenter retrospective study. Six University and Training Research Hospitals in Ankara participated in the study. We collected clinical data on patients (>18years) who received massive transfusions (≥10 units/24h) from 2017 through 2019. Overall, 167 (0·27% of transfused patients) received a massive transfusion of 2586 units of red blood cells (1·5% of total RBCs transfused). The median interquartile range values for RBCs, fresh frozen plasma (FFP) and platelets were 13 (11-176), 16 (9-33) and 4 (0-11), respectively. Surgical patients received 90% of massive transfusions. The most common clinical indications for massive transfusion were cardiovascular diseases (42·6%), trauma (20·3%) and malignancies (11%). FFP: RBC: Platelets ratio was 1·9:1:0·5. The overall and trauma-related mortality rates were 57·4% and 61·8%, respectively. The hospital mortality rates of trauma patients that received high vs. low ratio (FFP: RBCs>1:1·5 vs. ≤1:1·5) transfusions were 47·6% and 86·6% and the difference was statistically significant (P=0·03). Cardiovascular diseases and trauma occasion are the most common causes of massive transfusion. It is infrequent in clinical settings and is associated with high mortality rates. Additionally, in massively transfused trauma patients, a high FFP:RBCs ratio seems to be associated with increased survival. Focused prospective studies are required to define the areas that need improvement on a national scale.

Recent data from military and civilian centers suggest that mortality is decreased in massive transfusion patients by increasing the transfusion ratio of plasma and platelet (PLT) products, and fibrinogen in relationship to red blood cell (RBC) products during damage control resuscitation and surgery. This study investigates the relationship of plasma:RBC, PLT:RBC, and cryoprecipitate:RBC transfusion ratios to mortality in massively transfused patients at a civilian Level 1 trauma center. Demographic, laboratory, transfusion, and outcome data were collected prospectively from February 1, 2007, to January 31, 2009, and retrospectively from February 1, 2005, to January 31, 2007, on all injured patients who underwent massive transfusion (defined as >or=10 RBC products within 24 hr). Mortality was analyzed in relation to the plasma:RBC, PLT:RBC, and cryoprecipitate:RBC transfusion ratios using both univariate and multivariate analyses. A total of 214 patients received massive transfusion secondary to traumatic injury. High versus low transfusion ratios were associated with improved 30-day survival: plasma:RBC 59% versus 44%, p = 0.03; PLT:RBC 63% versus 33%, p < 0.01; and cryoprecipitate:RBC 66% versus 41%, p < 0.01. By multivariable stepwise logistic regression analysis, increased plasma:RBC (p = 0.02) and PLT:RBC (p = 0.02), and decreased age (p = 0.02), ISS (p < 0.01) and total RBCs (p = 0.03) were statistically associated with improved 30-day survival. In the civilian setting, plasma, PLT, and cryoprecipitate products significantly increased 30-day survival in trauma patients. Future prospective randomized clinical trials are required to determine the optimal transfusion ratios.

Optimal Plasma Transfusion in Patients Undergoing Cardiac Operations With Massive Transfusion

Massive Blood Transfusion in Patients with Ruptured Abdominal Aortic Aneurysm