Jeannie Callum

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

IMPORTANCE 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. OBJECTIVE 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. DESIGN, SETTING, AND PARTICIPANTS 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. INTERVENTIONS 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). MAIN OUTCOMES AND MEASURES 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. RESULTS 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. CONCLUSIONS AND RELEVANCE 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. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01545232.

Acute Kidney Injury After Cardiac Surgery Focus on Modifiable Risk Factors

Background— Acute kidney injury (AKI) after cardiac surgery is a major health issue. Lacking effective therapies, risk factor modification may offer a means of preventing this complication. The objective of the present study was to identify and determine the prognostic importance of such risk factors. Methods and Results— Data from a multicenter cohort of 3500 adult patients who underwent cardiac surgery at 7 hospitals during 2004 were analyzed (using multivariable logistic regression modeling) to determine the independent relationships between 3 thresholds of AKI (>25%, >50%, and >75% decrease in estimated glomerular filtration rate within 1 week of surgery or need for postoperative dialysis) with death rates, as well as to identify modifiable risk factors for AKI. The 3 thresholds of AKI occurred in 24% (n=829), 7% (n=228), and 3% (n=119) of the cohort, respectively. All 3 thresholds were independently associated with a >4-fold increase in the odds of death and could be predicted with several perioperative variables, including preoperative intra-aortic balloon pump use, urgent surgery, and prolonged cardiopulmonary bypass. In particular, 3 potentially modifiable variables were also independently and strongly associated with AKI. These were preoperative anemia, perioperative red blood cell transfusions, and surgical reexploration. Conclusions— AKI after cardiac surgery is highly prevalent and prognostically important. Therapies aimed at mitigating preoperative anemia, perioperative red blood cell transfusions, and surgical reexploration may offer protection against this complication.

Age of Transfused Blood in Critically Ill Adults

BACKGROUND Fresh red cells may improve outcomes in critically ill patients by enhancing oxygen delivery while minimizing the risks of toxic effects from cellular changes and the accumulation of bioactive materials in blood components during prolonged storage. METHODS In this multicenter, randomized, blinded trial, we assigned critically ill adults to receive either red cells that had been stored for less than 8 days or standard-issue red cells (the oldest compatible units available in the blood bank). The primary outcome measure was 90-day mortality. RESULTS Between March 2009 and May 2014, at 64 centers in Canada and Europe, 1211 patients were assigned to receive fresh red cells (fresh-blood group) and 1219 patients were assigned to receive standard-issue red cells (standard-blood group). Red cells were stored a mean (±SD) of 6.1±4.9 days in the fresh-blood group as compared with 22.0±8.4 days in the standard-blood group (P<0.001). At 90 days, 448 patients (37.0%) in the fresh-blood group and 430 patients (35.3%) in the standard-blood group had died (absolute risk difference, 1.7 percentage points; 95% confidence interval [CI], -2.1 to 5.5). In the survival analysis, the hazard ratio for death in the fresh-blood group, as compared with the standard-blood group, was 1.1 (95% CI, 0.9 to 1.2; P=0.38). There were no significant between-group differences in any of the secondary outcomes (major illnesses; duration of respiratory, hemodynamic, or renal support; length of stay in the hospital; and transfusion reactions) or in the subgroup analyses. CONCLUSIONS Transfusion of fresh red cells, as compared with standard-issue red cells, did not decrease the 90-day mortality among critically ill adults. (Funded by the Canadian Institutes of Health Research and others; Current Controlled Trials number, ISRCTN44878718.).

Reporting of near-miss events for transfusion medicine: improving transfusion safety

BACKGROUND: Half of the reported serious adverse events from transfusion are a consequence of medical error. A no‐fault medical‐event reporting system for transfusion medicine (MERS‐TM) was developed to capture and analyze both near‐miss and actual transfusion‐related errors.

Cryoprecipitate: The Current State of Knowledge

Cryoprecipitate is a diverse product containing factor VIII, von Willebrand factor, fibrinogen, fibronectin, factor XIII, and platelet microparticles. The role of this complex product in the management of hemostasis has not been well studied (excluding patients with factor VIII deficiency). There are insufficient data to determine the clinical setting where this product might be clinically efficacious despite its widespread use in multiple different clinical scenarios. The best method of pooling before transfusion has also not been thoroughly investigated to determine the optimal infusion strategy (intralaboratory vs bedside). The most common current indication for the use of this product is hypofibrinogenemia in the setting of massive hemorrhage. There are insufficient data in the literature to determine the efficacy, safety, and dosage in this patient population. Despite 45 years of the use of this product, we still have a lot to learn regarding the optimal use of cryoprecipitate.

Clinical review: Fresh frozen plasma in massive bleedings - more questions than answers.

Fresh frozen plasma (FFP) is indicated for the management of massive bleedings. Recent audits suggest physician knowledge of FFP is inadequate and half of the FFP transfused in critical care is inappropriate. Trauma is among the largest consumers of FFP. Current trauma resuscitation guidelines recommend FFP to correct coagulopathy only after diagnosed by laboratory tests, often when overt dilutional coagulopathy already exists. The evidence supporting these guidelines is limited and bleeding remains a major cause of trauma-related death. Recent studies demonstrated that coagulopathy occurs early in trauma. A novel early formula-driven haemostatic resuscitation proposes addressing coagulopathy early in massive bleedings with FFP at a near 1:1 ratio with red blood cells. Recent retrospective reports suggest such strategy significantly reduces mortality, and its use is gradually expanding to nontraumatic bleedings in critical care. The supporting studies, however, have bias limiting the interpretation of the results. Furthermore, logistical considerations including need for immediately available universal donor AB plasma, short life after thawing, potential waste and transfusion-associated complications have challenged its implementation. The present review focuses on FFP transfusion in massive bleeding and critically appraises the evidence on formula-driven resuscitation, providing resources to allow clinicians to develop informed opinion, given the current deficient and conflicting evidence.

Effect of a fixed-ratio (1:1:1) transfusion protocol versus laboratory-results–guided transfusion in patients with severe trauma: a randomized feasibility trial

Background: Hemorrhage coupled with coagulopathy remains the leading cause of preventable in-hospital deaths among trauma patients. Use of a transfusion protocol with a predefined ratio of 1:1:1 (1 each of red blood cells [RBC], frozen plasma [FP] and platelets) has been associated with improved survival in retrospective studies in military and civilian settings, but such a protocol has its challenges and may increase the risk of respiratory complications. We conducted a randomized controlled trial to assess the feasibility of a 1:1:1 transfusion protocol and its effect on mortality and complications among patients with severe trauma. Methods: We included 78 patients seen in a tertiary trauma centre between July 2009 and October 2011 who had hypotension and bleeding and were expected to need massive transfusion (≥ 10 RBC units in 24 h). We randomly assigned them to either the fixed-ratio (1:1:1) transfusion protocol (n = 40) or to a laboratory-results–guided transfusion protocol (control; n = 38). The primary outcome, feasibility, was assessed in terms of blood product ratios and plasma wastage. Safety was measured based on 28-day mortality and survival free of acute respiratory distress syndrome. Results: Overall, a transfusion ratio of 1:1:1 was achieved in 57% (21/37) of patients in the fixed-ratio group, as compared with 6% (2/32) in the control group. A ratio of 1:1 (RBC:FP) was achieved in 73% (27/37) in the fixed-ratio group and 22% (7/32) in the control group. Plasma wastage was higher with the intervention protocol (22% [86/390] of FP units v. 10% [30/289] in the control group). The 28-day mortality and number of days free of acute respiratory distress syndrome were statistically similar between the groups. Interpretation: The fixed-ratio transfusion protocol was feasible in our study, but it was associated with increased plasma wastage. Larger randomized trials are needed to evaluate the efficacy of such a protocol in trauma care. Trial registration: ClinicalTrials.gov, no. NCT00945542

The AABB recommendations for the Choosing Wisely campaign of the American Board of Internal Medicine.

C hoosing Wisely is an initiative of the American Board of Internal Medicine Foundation designed to help physicians and patients engage in conversations to reduce overuse of tests and procedures and support physician efforts to help patients make smart and effective care choices. Blood transfusion is the commonest procedure performed in the hospitalized patient. Unnecessary use of blood transfusion in the hospitalized patient is common worldwide. Overuse of blood transfusion has also been listed as a Choosing Wisely statement by the American Society of Hematology, the Society of Hospital Medicine, and the Critical Care Societies Collaborative. To support this AABB Choosing Wisely initiative, the AABB developed a set of 10 recommendations with input from AABB committees and the AABB Board of Directors. This list was vetted by numerous AABB members to select the top five statements as required by the American Board of Internal Medicine. As required, all of these statements start with “Don’t.” The development of these statements and commentaries are intended to assist you with the promotion of better patient blood management at your local institution. These statements are intended to prompt non– transfusion medicine physicians to rethink their engrained culture of liberal transfusion practice and prompt patients to question why they are being prescribed blood. 1. Don’t transfuse more units of blood than absolutely necessary A restrictive threshold (7.0-8.0g/dL) should be used for the vast majority of hospitalized, stable patients without evidence of inadequate tissue oxygenation (evidence supports a threshold of 8.0g/dL in patients with existing cardiovascular disease). Transfusion decisions should be influenced by symptoms and hemoglobin (Hb) concentration. Singleunit red blood cell (RBC) transfusions should be the standard for nonbleeding hospitalized patients. Additional units should only be prescribed after reassessment of the patient and their Hb value. A total of 13.8 million units of whole blood and RBCs were transfused in the United States in 2011 equating to 44 units per 1000 population, which is considerably higher than in other developed countries such as Australia, Canada, the Netherlands, and the United Kingdom where the rates of RBC transfusion are at least 25% lower. In common with those countries, the use of RBC units is decreasing in the United States; the rate was 48.8 per 1000 population in 2008. In 2011, there were approximately 21 million blood components transfused in the United States. Each transfusion carries risks, although the number of transfusion-related fatalities reported to the US Food and Drug Administration (58 in 2013) and the number of transfusion-related adverse reactions reported to the National Blood Collection and Utilization Survey (51,000 in 2011) remain small in comparison to the total number of transfusions. There is considerable variation in the use of blood between countries, hospitals, and even clinical teams within the same hospital. This observation has been documented over many years and in several clinical settings and probably indicates that a substantial amount of blood is being transfused inappropriately. The precise reasons for this variation are uncertain, but they include lack of knowledge about the evidence for the restrictive use of blood and inadequate feedback of comparative data on blood utilization. The number of published clinical practice guidelines for RBC transfusion including those on behalf of the AABB and the American College of Physicians attest to the interest in appropriate blood utilization. The guidelines generally acknowledge the necessity of considering ABBREVIATIONS: INR(s) = international normalized ratio(s); PCC(s) = prothrombin complex concentrate(s); RR = risk ratio.

Transfusion-Associated Hyperkalemia

The supernatant potassium concentration [K+] of red blood cell (RBC) units is frequently much higher than normal human plasma potassium levels, especially in units nearing the end of their storage life. Clinical hyperkalemia resulting from RBC transfusions has been recognized as a transfusion complication for decades, and there have been reported cardiac arrests attributed to transfusion-associated hyperkalemia. This review summarizes the evidence surrounding RBC [K+] levels, effects of irradiation and washing on [K+], the evidence for clinical hyperkalemia and cardiac arrests resulting from transfusion, predictors of post-transfusion hyperkalemia, and their preventative strategies. Key points include: (a) the [K+] (in mmol/L) increases linearly and is approximately equal to the number of days of RBC unit storage; (b) irradiation causes a rapid increase in [K+]; (c) there is potentially sufficient potassium in the supernatant of current RBC preparations to lead to hyperkalemia with large transfusion volumes; (d) any rise in patient potassium after transfusion is usually transient due to the redistribution of the potassium load; (e) transfusion-associated hyperkalemic cardiac arrests probably do occur, although it is difficult to prove this fact conclusively; and (f) promising strategies to combat transfusion-associated hyperkalemia include RBC washing, the use of in-line potassium filters, and the use of traditional treatments for hyperkalemia such as the use of insulin.

Expression of p210 and p190 BCR-ABL due to alternative splicing in chronic myelogenous leukaemia

The hallmark of chronic myelogenous leukaemia (CML) is the presence of the Philadelphia chromosome and its resultant fusion message, BCR‐ABL, and fusion protein, p210. Patients with CML in blast crisis, or with Philadelphia positive acute lymphoblastic leukaemia (ALL), can have a smaller BCR‐ABL fusion transcript possessing only the first exon of BCR fused to ABL. This smaller transcript encodes a 190 kD protein which is more strongly transforming than the p210 protein derived from the larger CML‐associated transcript. We performed RT‐PCR on samples from CML patients in chronic phase to determine the frequency and mechanism of p190 and p210 co‐expression and to see if this correlated with clinical indices.