Improved outcomes and reduced complications were associated with a restrictive transfusion strategy in patients with upper gastrointestinal bleeding. Note that patients with “massive exsanguinating bleeding” were excluded from the study so this shouldn’t be extrapolated to such presentations.
The benefit seemed to be most marked in patients with variceal haemorrhage, but not those with the most severe Child-Pugh class. In portal hypertensive-related bleeding, transfusion may increase portal pressure and exacerbate bleeding.
The patients were ‘scoped within 6 hours, and less than 10% received FFP or platelets. Both groups averaged over 5 litres of crystalloid in the first 72 hours.
Transfusion Strategies for Acute Upper Gastrointestinal Bleeding
N Engl J Med. 2013 Jan 3;368(1):11-21
BACKGROUND: The hemoglobin threshold for transfusion of red cells in patients with acute gastrointestinal bleeding is controversial. We compared the efficacy and safety of a restrictive transfusion strategy with those of a liberal transfusion strategy.
METHODS: We enrolled 921 patients with severe acute upper gastrointestinal bleeding and randomly assigned 461 of them to a restrictive strategy (transfusion when the hemoglobin level fell below 7 g per deciliter) and 460 to a liberal strategy (transfusion when the hemoglobin fell below 9 g per deciliter). Randomization was stratified according to the presence or absence of liver cirrhosis.
RESULTS: A total of 225 patients assigned to the restrictive strategy (51%), as compared with 61 assigned to the liberal strategy (14%), did not receive transfusions (P<0.001) [corrected].The probability of survival at 6 weeks was higher in the restrictive-strategy group than in the liberal-strategy group (95% vs. 91%; hazard ratio for death with restrictive strategy, 0.55; 95% confidence interval [CI], 0.33 to 0.92; P=0.02). Further bleeding occurred in 10% of the patients in the restrictive-strategy group as compared with 16% of the patients in the liberal-strategy group (P=0.01), and adverse events occurred in 40% as compared with 48% (P=0.02). The probability of survival was slightly higher with the restrictive strategy than with the liberal strategy in the subgroup of patients who had bleeding associated with a peptic ulcer (hazard ratio, 0.70; 95% CI, 0.26 to 1.25) and was significantly higher in the subgroup of patients with cirrhosis and Child-Pugh class A or B disease (hazard ratio, 0.30; 95% CI, 0.11 to 0.85), but not in those with cirrhosis and Child-Pugh class C disease (hazard ratio, 1.04; 95% CI, 0.45 to 2.37). Within the first 5 days, the portal-pressure gradient increased significantly in patients assigned to the liberal strategy (P=0.03) but not in those assigned to the restrictive strategy.
CONCLUSIONS: As compared with a liberal transfusion strategy, a restrictive strategy significantly improved outcomes in patients with acute upper gastrointestinal bleeding. (Funded by Fundació Investigació Sant Pau; ClinicalTrials.gov number, NCT00414713.).
The observation that patients with haemorrhagic trauma in military and civilian settings do better if they receive coagulation factors and platelets is yet to be replicated in a randomised trial. It has been suggested that the effect may in part be a consequence of survivor bias – ie. that if a patient lives long enough to received some thawed fresh frozen plasma, then they were already more likely to be a survivor and therefore more survivors will be represented in the ‘FFP’ groups vs a ‘no-FFP’ comparison group.
An attempt to eliminate survivor bias was made in the PROMMTT study, which documented the timing of transfusions during active resuscitation and patient outcomes in adult trauma patients who received a transfusion of at least 1 unit of RBCs within 6 hours of admission.
Increased ratios of plasma:RBCs and platelets:RBCs were independently associated with decreased 6-hour mortality, when haemorrhagic 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.
A prospective trial is underway to identify the optimal ratio of blood products, in the PROPPR study, in which 1:1:1 ratio of plasma:platelets:RBC will be compared with 1:1:2.
The Prospective, Observational, Multicenter, Major Trauma Transfusion (PROMMTT) Study
Arch Surg. 2012 Oct 15:1-10
Objective: 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.
Design: Prospective cohort study documenting the timing of transfusions during active resuscitation and patient outcomes. Data were analyzed using time-dependent proportional hazards models.
Setting: Ten US level I trauma centers.
Patients: 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).
Main Outcome Measure: In-hospital mortality.
Results: 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.
Conclusions: 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.
The group usually considered the universal donor for fresh frozen plasma because it contains no anti-A or anti-B antibodies is Type AB. Due to its limited availability the trauma service of the Mayo Clinic in Minnesota has been issuing thawed group A plasma to its flight crews who retrieve major trauma casualties from rural centres. This is given with packed group O red cells to patients who meet their prehospital massive transfusion protocol criteria. Some patients will inevitably receive ABO-incompatible plasma (namely patients with Group B or AB blood) which could theoretically give rise to haemolytic transfusion reactions, in which donor antibodies bind host red cells, activate complement, and give rise to anaemia, disseminated intravascular coagulation, acute kidney injury, and death. However:
- the transfusion of platelets containing ABO-incompatible plasma is common, with up to 2 units of incompatible plasma per apheresis platelet unit, whereas haemolytic reactions to platelets are rare (1 in 9,000 incompatible platelet transfusions);
- all reports of haemolytic reactions are caused by products that contain Group O plasma and there has never been a documented case of haemolysis as a result of products containing Group A plasma
A retrospective review showed no increased rates of adverse events with Type A compared with AB or ABO-compatible plasma. Since only a small absolute number of patients received an ABO-incompatible plasma transfusion, it could be argued that the study is underpowered (a point acknowledged by the authors). However this is very important and useful information for resource-limited settings.
Emergency use of prethawed Group A plasma in trauma patients
J Trauma Acute Care Surg. 2013 Jan;74(1):69-74
BACKGROUND: Massive transfusion protocols lead to increased use of the rare universal plasma donor, Type AB, potentially limiting supply. Owing to safety data, with a goal of avoiding shortages, our blood bank exploited Group A rather than AB for all emergency release plasma transfusions. We hypothesized that ABO-incompatible plasma transfusions had mortality similar to ABO-compatible transfusions.
METHODS: Review of all trauma patients receiving emergency release plasma (Group A) from 2008 to 2011 was performed. ABO compatibility was determined post hoc. Deaths before blood typing were eliminated. p < 0.05 was considered statistically significant.
RESULTS: Of the 254 patients, 35 (14%) received ABO-incompatible and 219 (86%) received ABO-compatible transfusions. There was no difference in age (56 years vs. 59 years), sex (63% vs. 63% male), Injury Severity Score (ISS) (25 vs. 22), or time spent in the trauma bay (24 vs. 26.5 minutes). Median blood product units transfused were similar: emergency release plasma (2 vs. 2), total plasma at 24 hours (6 vs. 4), total red blood cells at 24 hours (5 vs. 4), plasma-red blood cells at 24 hours (1.3:1 vs. 1.1:1), and plasma deficits at 24 hours (2 vs. 1). Overall complications were similar (43% vs. 35%) as were rates of possible transfusion-related acute lung injury (2.9% vs. 1.8%), acute lung injury (3.7% vs. 2.5%), adult respiratory distress syndrome (2.9% vs. 1.8%), deep venous thrombosis (2.9% vs. 4.1%), pulmonary embolism (5.8% vs. 7.3%), and death (20% vs. 22%). Ventilator (6 vs. 3), intensive care unit (4 vs. 3), and hospital days (9 vs. 7) were similar. There were no hemolytic reactions. Mortality was significantly greater for the patients who received incompatible plasma if concurrent with a massive transfusion (8% vs. 40%, p = 0.044). Group AB plasma use was decreased by 96.6%.
CONCLUSION: Use of Group A for emergency release plasma resulted in ABO-incompatible transfusions; however, this had little effect on clinical outcomes. Blood banks reticent to adopt massive transfusion protocols owing to supply concerns may safely use plasma Group A, expanding the pool of emergency release plasma donors.
LEVEL OF EVIDENCE: Therapeutic study, level IV; prognostic study, level III.
The AABB (formerly the American Association of Blood Banks has issued guidelines on red blood cell transfusion1, providing some number-based targets which may be helpful for some practitioners or organisations. Editorialist and heavyweight intensivist Jean-Louis Vincent argues for a more individual patient-based assessment2, and highlights some of the weaknesses of existing studies, in particular the often quoted but now fairly old TRICC study3 which suffered from poor recruitment and the possible lack of applicability to modern practice now that leucodepleted products are used.
Prof Vincent states:
“Transfusion decisions need to consider individual patient characteristics, including age and the presence of CAD, to estimate a specific patient’s likelihood of benefit from transfusion. The decision to transfuse is too complex and important to be guided by a single number.”
Description: Although approximately 85 million units of red blood cells (RBCs) are transfused annually worldwide, transfusion practices vary widely. The AABB (formerly, the American Association of Blood Banks) developed this guideline to provide clinical recommendations about hemoglobin concentration thresholds and other clinical variables that trigger RBC transfusions in hemodynamically stable adults and children.
Methods: These guidelines are based on a systematic review of the literature on randomized clinical trials evaluating transfusion thresholds. We performed a literature search from 1950 to February 2011 with no language restrictions. We examined the proportion of patients who received any RBC transfusion and the number of RBC units transfused to describe the effect of restrictive transfusion strategies on RBC use. To determine the clinical consequences of restrictive transfusion strategies, we examined overall mortality, nonfatal myocardial infarction, cardiac events, pulmonary edema, stroke, thromboembolism, renal failure, infection, hemorrhage, mental confusion, functional recovery, and length of hospital stay.
Recommendation 1: The AABB recommends adhering to a restrictive transfusion strategy (7 to 8 g/dL) in hospitalized, stable patients (Grade: strong recommendation; high-quality evidence).
Recommendation 2: The AABB suggests adhering to a restrictive strategy in hospitalized patients with preexisting cardiovascular disease and considering transfusion for patients with symptoms or a hemoglobin level of 8 g/dL or less (Grade: weak recommendation; moderate-quality evidence).
Recommendation 3: The AABB cannot recommend for or against a liberal or restrictive transfusion threshold for hospitalized, hemodynamically stable patients with the acute coronary syndrome (Grade: uncertain recommendation; very low-quality evidence).
Recommendation 4: The AABB suggests that transfusion decisions be influenced by symptoms as well as hemoglobin concentration (Grade: weak recommendation; low-quality evidence).
1. Red Blood Cell Transfusion: A Clinical Practice Guideline From the AABB
Ann Intern Med. 2012 Mar 26. [Epub ahead of print] Full Text
2. Indications for Blood Transfusions: Too Complex to Base on a Single Number?
Ann Intern Med. 2012 Mar 26. [Epub ahead of print] Full Text
3. A Multicenter, Randomized, Controlled Clinical Trial of Transfusion Requirements in Critical Care
N Engl J Med 1999; 340:409-417 Full Text
In some circles, ‘wuntwuntwun’ is in danger of becoming the new dogma of trauma fluid replacement (ie. 1 unit of plasma and 1 unit of platelets for every unit of red cells). Since it takes longer to thaw some plasma than it does to throw in some O negative packed red cells, some really sick patients may be dead before they get the plasma, biasing comparisons that show a reduced mortality in patients who were still alive to receive plasma. This ‘survivor bias’ has been suggested as a reason that high plasma:red cell ratios are associated with mortality reduction, although this has been challenged.
The survivor bias explanation receives some new support by the following (small) study from Journal of Trauma:
BACKGROUND: In light of recent data, controversy surrounds the apparent 30-day survival benefit of patients achieving a fresh frozen plasma (FFP) to packed red blood cell (PRBC) ratio of at least 1:2 in the face of massive transfusions (MT) (≥10 units of PRBC within 24 hours of admission). We hypothesized that initial studies suffer from survival bias because they do not consider early deaths secondary to uncontrolled exsanguinating hemorrhage. To help resolve this controversy, we evaluated the temporal relationship between blood product administration and mortality in civilian trauma patients receiving MT.
METHODS: Patients requiring MT over a 22-month period were identified from the resuscitation registry of a Level I trauma center. Shock severity at admission and timing of shock-trauma admission, blood product administration, and death were determined. Patients were divided into high- and low-ratio groups (≥1:2 and<1:2 FFP:PRBC, respectively) and compared. Kaplan-Meier analysis and log-rank test was used to examine 24-hour survival.
RESULTS: One hundred three patients (63% blunt) were identified (66 high-ratio and 37 low-ratio). Those patients who achieved a high-ratio in 24 hours had improved survival. However, severity of shock was less in the high-group (base excess: -8.0 vs. -11.2, p=0.028; lactate: 6.3 vs. 8.4, p=0.03). Seventy-five patients received MT within 6 hours. Of these, 29 received a high-ratio in 6 hours. Again, severity of shock was less in the high-ratio group (base excess: -7.6 vs. -12.7, p=0.008; lactate: 6.7 vs. 9.4, p=0.02). For these patients, 6-hour mortality was less in the high-group (10% vs. 48%, p<0.002). After accounting for early deaths, groups were similar from 6 hours to 24 hours.
CONCLUSIONS: Improved survival was observed in patients receiving a higher plasma ratio over the first 24 hours. However, temporal analysis of mortality using shorter time periods revealed those who achieve early high-ratio are in less shock and less likely to die early from uncontrolled hemorrhage compared with those who never achieve a high-ratio. Thus, the proposed survival advantage of a high-ratio may be because of selection of those not likely to die in the first place; that is, patients die with a low-ratio not because of a low-ratio.
The authors state “The current study underscores the need for well-designed prospective studies to address the important question of which ratio results in improved survival and stresses the importance of timing of blood product administration as this may impact survival.”
Improved survival after hemostatic resuscitation: does the emperor have no clothes?
J Trauma. 2011 Jan;70(1):97-102
In major trauma patients who require blood transfusion, fresh frozen plasma (FFP) to packed red blood cell (RBC) ratios of up to 1:1 have been associated with reduced mortality in retrospective studies, which may be in part due to survival bias (some patients die before they can be given as much FFP as the survivors).
To eliminate this bias, Australian researchers reviewed 331 trauma patients receiving at least 5 units of red cells in the first 4 hours, with a median Injury Severity Score of 36. When deaths in the first 24 hours were excluded, FFP:RBC ratio had no association with mortality. They conclude that prospective randomised controlled trials are needed.
Fresh frozen plasma (FFP) use during massive blood transfusion in trauma resuscitation
Injury. 2010 Jan;41(1):35-9
Blood transfusion in trauma is a risk factor for acute respiratory distress syndrome (ARDS). An analysis of 14070 patients in a trauma database showed that 521 (4.6%) developed ARDS. Logisitc regression analysis demonstrated that, independent of injury type, injury severity, or pneumonia, (1) early PRBCs transfusion of more than 5 units during the ﬁrst 24 h of hospital admission predicted ARDS and (2) each unit of PRBCs transfused early after admission increased the risk of ARDS by 6%.
Early packed red blood cell transfusion and acute respiratory distress syndrome after trauma.
Anesthesiology. 2009 Feb;110(2):351-60