Large-volume Transfusion Research Articles

The Efficacy of Traumatic Brain Injury Treatment by Neurotrauma Specialists.

Since the establishment of Regional Trauma Centers (RTCs) in Korea, significant efforts have been made to improve the quality of care for patients with trauma. Simultaneously, the Department of Neurosurgery assigned neurotrauma specialists to RTCs to provide specialized care to patients with traumatic brain injury (TBI). In this study, we sought to determine whether neurotrauma specialists, compared to general neurosurgeons, could make a significant difference in treatment outcomes of patients with TBI. In total, 156 patients with acute TBI who required decompression were included. We reviewed their records and compared the characteristics, outcomes, and prognosis of those who received surgical treatment from either neurotrauma specialists or general neurosurgeons at our institution. A significant difference was observed between treatment by trauma neurosurgery specialists and general neurosurgeons in time to surgery, with trauma specialists experiencing shorter surgical delays. However, no significant differences existed in mortality rates or Extended Glasgow Outcome Scale scores. Univariate and multivariable regression analyses revealed that lower Glasgow Coma Scale scores, an abnormal pupil reflex, larger transfusion volume, and prolonged time from emergency room admission to surgery were associated with high mortality rates. Neurotrauma specialists can provide prompt surgical treatment to patients with TBI compared to general neurosurgeons. Our study did not reveal a significant difference in outcomes between the two groups. However, it is clear that rapid decompression is effective in patients with impending brain herniation. Therefore, the effectiveness of neurotrauma specialists needs to be confirmed through further systematic studies.

Effect of postoperative delirium after cardiovascular surgery on 5-year mortality

IntroductionPostoperative delirium is a common complication after cardiovascular surgery. A meta-analysis revealed that postoperative delirium was associated with cognitive decline and dementia, which may affect long-term mortality. However, few studies have reported the association between postoperative delirium after cardiovascular surgery and long-term postoperative mortality. Therefore, we investigated the effect of postoperative delirium on 5-year survival rates of patients who underwent cardiovascular surgery.MethodsWe retrospectively reviewed the records of patients who underwent cardiovascular surgery with cardiopulmonary bypass from January 2016 to December 2019. Postoperative delirium was defined as an Intensive Care Delirium Screening score ≥ 3, which might include subclinical delirium. Cox proportional hazards modeling was performed to assess the association between postoperative delirium and mortality. Postoperative mortality in patients with and without delirium was assessed using the Kaplan–Meier method and compared using the log-rank test.ResultsPostoperative delirium was observed in 562 (31.9%) of 1731 patients. There were more elderly patients, more emergent surgery procedures, longer operative time, and larger transfusion volume in the postoperative delirium group. Cox regression analyses showed that delirium (hazard ratio (HR), 1.501; 95% confidence interval (CI), 1.053–2.140; p = 0.025) and emergent surgery (HR, 3.380; 95% CI, 2.231–5.122; p < 0.001) are significantly associated with 5-year mortality. Among patients who underwent elective surgery, postoperative delirium (HR, 1.987; 95% CI, 1.135–3.481; p = 0.016) is significantly associated with 5-year mortality. Kaplan–Meier survival analysis revealed that patients with postoperative delirium had significantly higher 5-year mortality.ConclusionsPatients with postoperative delirium after cardiovascular surgery have significantly higher 5-year mortality.

Hypocalcemia in Trauma is Determined by the Number of Units Transfused, Not Whole Blood Versus Component Therapy

IntroductionBlood component resuscitation is associated with hypocalcemia (HC) (iCal <0.9 mmol/L) that contributes to coagulopathy and death in trauma patients. It is unknown whether or not whole blood (WB) resuscitation helps mitigate the risk of HC in trauma patients. We hypothesized that calcium homeostasis is maintained and mortality improved in patients who only receive WB. Materials and methodsThis is a retrospective review of all adult trauma patients who received WB from July 2018 to December 2020. Variables included transfusions, ionized calcium levels, and calcium replacement. Patients were characterized as follows based on blood products received: WB or WB with other blood components. Groups were compared with respect to HC, correction of HC, 24 h, and inpatient mortality. ResultsTwo hundred twenty-three patients received WB and met the inclusion criteria. 107 (48%) received WB only. HC occurred in 13% of patients who received more than one WB unit compared to 29% of WB and other blood component patients (P = 0.02). WB patients received less calcium replacement (median 250 mg versus 2000 mg, P < 0.01). HC and total units transfused within 4 h were associated with mortality in the adjusted model. HC significantly increased after 5 units of blood products were transfused, regardless of product type. WB was not protective against HC. ConclusionsHC and failure to correct HC are significant risk factors for mortality in trauma. Resuscitations with WB only and WB in combination with other blood components are associated with HC especially when more than 5 units of any blood product are transfused. Calcium supplementation should be prioritized in any large volume transfusion, regardless of blood product type.

Packed Red Blood Cell Transfusion as a Predictor of Moderate-Severe Bronchopulmonary Dysplasia: A Comparative Cohort Study of Very Preterm Infants.

Bronchopulmonary dysplasia (BPD) is a leading cause of morbidity and mortality in neonatal intensive care units. Our aim was to evaluate association between packed red blood cell transfusion and the development of BPD in very preterm infants. This retrospective study of very preterm infants (mean gestational age: 27.1 ± 2.4 weeks, birth weight: 970 ± 271 g) was conducted at Biruni University (Turkey) between July 2016 and December 2020. BPD developed in 107 of the 246 enrolled neonates, including 47 (43.9%), 27 (25.3%), and 33 (30.8%) diagnosed with mild, moderate, and severe BPD, respectively. A total of 728 transfusions were administered. The increased number (4 transfusions [2-7] vs. 1 [1-3], p = 0.001) and volume of transfusions (75 mL/kg volume [40-130] vs. 20 [15-43], p = 0.001) were significantly higher in infants with BPD compared to those without BPD. The transfusion volume cut-off for the prediction of BPD by receiver operating characteristic curve analysis was 42 mL/kg (sensitivity 73.6%; specificity 75%; area under the receiver-operating characteristic curve: 0.82). In multivariate analysis, multiple transfusions and larger transfusion volume were independent risk factors for moderate-severe BPD. The increased number and volume of transfusions were associated with BPD in very preterm infants. A packed red blood cell transfusion volume ≥42 mL/kg was a statistically significant predictor of the development of BPD at a postmenstrual age of 36 weeks. · Transfusions were found to be an important risk factor for BPD development in very premature infants.. · Number and volume of transfusion were associated with the severity of BPD.. · Optimal cut point volume of transfusion for prediction of BPD was 42 mL/kg body weight..

Use of Bayesian Statistics to Reanalyze Data From the Pragmatic Randomized Optimal Platelet and Plasma Ratios Trial

Frequentist statistical approaches are the most common strategies for clinical trial design; however, bayesian trial design may provide a more optimal study technique for trauma-related studies. To describe the outcomes of bayesian statistical approaches using data from the Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) Trial. This quality improvement study performed a post hoc bayesian analysis of the PROPPR Trial using multiple hierarchical models to assess the association of resuscitation strategy with mortality. The PROPPR Trial took place at 12 US level I trauma centers from August 2012 to December 2013. A total of 680 severely injured trauma patients who were anticipated to require large volume transfusions were included in the study. Data analysis for this quality improvement study was conducted from December 2021 and June 2022. In the PROPPR Trial, patients were randomized to receive a balanced transfusion (equal portions of plasma, platelets, and red blood cells [1:1:1]) vs a red blood cell-heavy strategy (1:1:2) during their initial resuscitation. Primary outcomes from the PROPPR trial included 24-hour and 30-day all-cause mortality using frequentist statistical methods. Bayesian methods were used to define the posterior probabilities associated with the resuscitation strategies at each of the original primary end points. Overall, 680 patients (546 [80.3%] male; median [IQR] age, 34 [24-51] years, 330 [48.5%] with penetrating injury; median [IQR] Injury Severity Score, 26 [17-41]; 591 [87.0%] with severe hemorrhage) were included in the original PROPPR Trial. Between the groups, no significant differences in mortality were originally detected at 24 hours (12.7% vs 17.0%; adjusted risk ratio [RR], 0.75 [95% CI, 0.52-1.08]; P = .12) or 30 days (22.4% vs 26.1%; adjusted RR, 0.86 [95% CI, 0.65-1.12]; P = .26). Using bayesian approaches, a 1:1:1 resuscitation was found to have a 93% (Bayes factor, 13.7; RR, 0.75 [95% credible interval, 0.45-1.11]) and 87% (Bayes factor, 6.56; RR, 0.82 [95% credible interval, 0.57-1.16]) probability of being superior to a 1:1:2 resuscitation with regards to 24-hour and 30-day mortality, respectively. In this quality improvement study, a post hoc bayesian analysis of the PROPPR Trial found evidence in support of mortality reduction with a balanced resuscitation strategy for patients in hemorrhagic shock. Bayesian statistical methods offer probability-based results capable of direct comparison between various interventions and should be considered for future studies assessing trauma-related outcomes.

Transfusion-reducing techniques decrease perioperative morbidity of Cesarean hysterectomy for placenta accreta spectrum

Placenta accreta spectrum (PAS) is associated with high rates of hemorrhage and serious morbidity. Transfusion-reducing techniques have been used successfully in cardiac surgery to decrease blood loss and blood utilization. The purpose of this study is to evaluate the impact of these techniques on perioperative morbidity for women undergoing Cesarean hysterectomy for PAS. This cohort study was performed at a tertiary center between 2011-2021 and compared women with prenatally-diagnosed PAS undergoing Cesarean hysterectomy with transfusion-reducing techniques to those having the procedure without. Emergent cases and those with incidentally encountered PAS at delivery were excluded. The treatment group protocol involved iron supplementation, tranexamic acid (TXA), the LigaSure vessel sealing system, intraoperative ultrasound-guided placental mapping, and intraoperative blood salvage (Cell Saver). Outcomes were estimated blood loss (EBL), rates of overall and large-volume transfusion (≥4 units packed red blood cells [pRBC]), and intensive care unit (ICU) utilization. Statistical analysis included chi-square, t-test, or Mann-Whitney U test, with p< 0.05 designated for statistical significance. Of the 55 patients studied, 35 were in the transfusing-reducing group and 20 were in the control group. Groups were similar in terms of age, body mass index, parity, and uterine surgical history; the transfusion-reducing group had higher use of iron, TXA, LigaSure, and placental mapping (Table 1). There was decreased EBL (median 1500 (750 – 2000mL) vs. 2750 (1850 – 3500mL), p < .001), overall transfusion (n=15 (43%) vs. n=17 (85%), p=.004), ≥4 units pRBC transfusion (n=5 (14%) vs. n=12 (60%), p< .001) and ICU admission (n=9 (26%) vs. n=18 (90%), p< .001) in the treatment group (Table 2). Surgical blood loss and blood transfusion can be safely reduced in patients undergoing scheduled Cesarean hysterectomy for suspected PAS by using the principles of transfusion-reducing surgery.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Optimizing Use of Automated Isovolemic Hemodilution Red-Cell Exchange in a Patient Cohort with Sickle Cell Disease: A Quality Improvement Intervention

Background: Red-cell exchange (RCE) is a mainstay of treatment for both acute and chronic complications of sickle cell disease (SCD). It is a resource-intensive intervention requiring transfusion of large volumes of antigen-matched red blood cells (RBC). Identifying suitable RBC units can be challenging due to variability in blood group phenotypes between patients with SCD and the donor population. This often results in use of O-negative units, which are a scarce resource. Efforts to reduce the volume of units transfused, while maintaining therapeutic efficacy is an important clinical need. Isovolemic hemodilution (IHD) prior to RCE reduces the required volume of RBCs. The aim of this project is to evaluate the effect of a change to IHD-RCE on RBC utilization in patients with SCD receiving standard RCE. Methods: All adult SCD patients receiving standard RCE at the Ottawa Hospital were identified. To safely attain a meaningful reduction in transfused RBCs, RCE treatment parameters were individualized for each patient (Table 1). Patient hematocrit was not allowed to decrease below 20% during the depletion phase, and IHD-RCE would be performed only if an estimated reduction in RBC volume of at least 200 mL was expected. Pregnant patients were excluded. Change in RCE protocol to IHD-RCE took place in January 2022. Transfusion and clinical data were obtained from databases at the Ottawa Hospital in the six months preceding and succeeding the change in RCE protocols to allow for a pre- and post-intervention comparison. Results: Thirty-four adults receiving regular RCE for SCD were identified. Twenty-two patients met criteria for a protocol change to IHD-RCE. The mean age of the IHD-RCE cohort was 31 years (SD 9.5). Males comprised 72.7% of this cohort, with the most frequent genotype of hemoglobin SS (68.2%). Over the one-year study period, 1963 RBC units were transfused: 1035 RBC units in the pre-intervention period, and 928 units in the post-intervention period, representing a reduction of 107 RBC units. 1958 (99.7%) of the RBC units transfused were transfused in the setting of RCE, with few (5 units; 0.03%) administered as simple RBC transfusions. Table 2 outlines patient outcomes during the study period. The mean number of RBC units transfused per patient in the pre- and post-intervention periods were 47 and 42.4 units, respectively. The mean number of RBC units per RCE session per patient was significantly reduced from 8.7 units in the pre-intervention period to 7.8 units in the IHD-RCE post-intervention period (mean difference: -0.9, 95% CI: -1.2 to -0.5). A total of 236 RCE sessions occurred during the study period. No difference in RCE session frequency was observed with a change to IHD-RCE during the six-month study period, nor time between RCE sessions. Therapeutic efficacy in attaining target hemoglobin S levels was not affected by the change to IHD-RCE. No adverse patient safety signals were observed during the IHD-RCE sessions to date. Conclusions: This study demonstrates that IHD-RCE, compared to standard RCE, substantially reduces RBC utilization. A total of 107 RBC units were conserved in our patient cohort of 22 chronic RCE patients directly from the transition to IHD-RCE from standard RCE. Based on local RBC per unit costs, this corresponds to an annualized saving of $95,444 CAD. With pressure on blood banks to provide appropriately matched units, and risks of alloimmunization and delayed hemolytic transfusion reactions amongst chronically transfused SCD patients, increased uptake of IHD-RCE should be considered for SCD patients on chronic RCE. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

S2586 Don’t Get 2 Comfortable: A Rare Case of Meckel’s Diverticulum Causing Hemorrhagic Shock in an Adult

Introduction: Meckel’s diverticulum (MD) is a true diverticulum that results from incomplete obliteration from the vitelline duct during embryonic development. It is a one of the most common congenital disorders of the gastrointestinal (GI) tract. Often characterized using “The Rule of 2’s”: MD occurs in approximately 2% of the population, is 2 inches long, is within 2 feet from the ileocecal valve, is twice as common in males than females, can contain 2 types of tissue (gastric or pancreatic), 2% become symptomatic, and most present before the age of 2. The majority of symptomatic MD occur as painless hematochezia in children and therefore is often lower on the differential of an adult with a GI bleed. Even when MD is suspected as an etiology for GI bleeding in an adult, the evaluation can be challenging. Case Description/Methods: A 25-year-old male with no significant past medical history was admitted to the hospital for GI bleeding and then developed hemorrhagic shock requiring resuscitation with transfusion of large volumes of blood products. The etiology of his GI bleed remained elusive for several days despite evaluation with upper endoscopy, three colonoscopies, three CT angiograms of the abdomen and pelvis, and a video capsule endoscopy. Subsequently, he underwent two separate fluoroscopic angiograms with interventional radiology. While the first angiogram was unrevealing, the second angiogram demonstrated a tortuous ileal artery branch with active extravasation that was treated with embolization. Given IR findings, a Meckel’s scan was performed which was negative. A multi-disciplinary review of the case prompted further review of the patient’s abdominal CT angiogram and a potential finding of MD was seen at the distal ileum. Ultimately, the surgery team decided to take the patient to the operating room where they found and resected a segment of small bowel with tissue examination revealing the MD (Figure 1). Discussion: A Meckel’s scan is often considered the modality of choice for diagnosing MD in children, however, its diagnostic accuracy is considered to be much lower in adults. The typical approach to GI bleeding via upper endoscopy, colonoscopy, capsule endoscopy, CT and procedural angiography may be negative, as seen in our case. Balloon assisted enteroscopy, where available, may also be a potentially useful tool for diagnosing MD. This case highlights the importance of maintaining a broad differential diagnosis for GI bleeding and the challenges with current diagnostic modalities.Figure 1.: Meckel's diverticulum at the level of distal small bowel, approximately 60 cm from the ileocecal valve.

Fibronectin: structure, functions, clinical significance (review)

Plasma fibronectin is a high molecular weight adhesive glycoprotein. There are two types of fibronectin: plasma (soluble) and cellular derived (insoluble). Electron microscopy revealed two types of structural organization of fibronectin: compact and expanded. In solution, fibronectin has a compact conformation, and after binding to certain substrates (collagen, fibrin, heparin), it is expanded. Plasma fibronectin is one of the main opsonins of blood plasma in relation to the “targets” of phagocytosis of a predominantly non-bacterial nature, as well as to some types of bacteria. For the treatment of septic processes, as well as respiratory distress syndrome of adults with severe fibronectin deficiency, plasma cryoprecipitate is used – a donor plasma preparation containing a large amount of plasma fibronectin (more than 2 mg/ml). It was proposed to replenish the level of fibronectin in patients with sepsis and other conditions that cause plasma fibronectin deficiency with the help of donor freshly frozen plasma. Transfusion of large volumes of freshly frozen plasma (up to 1000–1500 ml) to patients effectively eliminates the deficiency of plasma fibronectin. The concentration of plasma fibronectin in the blood significantly decreases after the addition of severe infectious processes to hematological diseases, as well as acute DIC syndrome. Extracorporeal methods of blood purification – selective plasmapheresis – have been developed to correct immunocomplex and fibronectin-complex pathology. Two variants of selective plasmapheresis have been proposed: the method of heparinocryoprecipitation of plasma proteins and the method of heparinocryofractionation. In 1987, a plasma heparin precipitate was proposed as a source of fibronectin for the treatment of patients with trophic skin lesions. In 1992, a new method was proposed for obtaining blood preparations with a high concentration of plasma fibronectin from patients themselves (heparin cryofractionation). Autofibronectin preparations obtained by such methods are effective in the local treatment of trophic ulcers in 90–93% of cases. The proposed drugs are safe against infection of patients with infectious diseases transmitted through the blood.

Elevated international normalized ratio is correlated with large volume transfusion in pediatric trauma patients

BackgroundPediatric trauma patients may benefit from a balanced transfusion strategy, however, determining when to activate massive transfusion protocols remains uncertain. The purpose of this study was to explore whether certain scoring systems can predict the need for large volume transfusion. MethodsWe conducted a retrospective review of pediatric trauma patients who presented to our center and required a transfusion of packed red blood cells. Baseline laboratory and clinical data were used to calculate Trauma Associated Severe Hemorrhage (TASH) score and a previously reported composite of acidosis and coagulopathy. ResultsWe identified 518 pediatric trauma patients who presented to our center between January 1, 2013 and December 31, 2018. These patients were less than 18 years of age (mean 9.6 years) and had an injury severity score ranging from 1 to 50 (mean 11.3). Forty-three patients (8.3%) received a transfusion within 24 hours of presentation, ranging from 4 to 139 mL/kg of packed red blood cells (mean 23.1 mL/kg). Transfusion volume was associated with acidosis and coagulopathy scores (r = 0.37, p = 0.033) and international normalized ratio (INR) (r = 0.34, p = 0.03) but not TASH (p = 0.72). Patients with INR≥1.3 received a higher mean volume of packed red cells compared to those with normal values (34 versus 18 mL/kg, p = 0.046). ConclusionPediatric trauma patients who undergo transfusion of packed red blood cells are likely to require large volume transfusion if their baseline INR is ≥1.3. These patients may benefit from a balanced transfusion strategy, such as utilization of massive transfusion protocols or whole blood.

Place of birth and outcomes associated with large volume transfusion: an observational study

BackgroundGuidelines recommend that women at high risk of postpartum haemorrhage deliver at facilities able to handle heavy bleeding. However postpartum haemorrhage is often unexpected. This study aims to compare outcomes and health service use related to transfusion of ≥4 units of red blood cells between women delivering in tertiary and lower level hospitals.MethodsThe study population was women giving birth in public hospitals in New South Wales, Australia, between July 2006 and December 2010. Data were obtained from linked hospital, birth and blood bank databases. The exposure of interest was transfusion of four or more units of red cells during admission for delivery. Outcomes included maternal morbidity, length of stay, neonatal morbidity and need for other blood products or transfer to higher care. Multivariable regression models were developed to predict need of transfusion of ≥4 units of red cells using variables known early in pregnancy and those known by the birth admission.ResultsData were available for 231,603 births, of which 4309 involved a blood transfusion, with 1011 (0.4%) receiving 4 or more units. Women giving birth in lower level and/or smaller hospitals were more likely to receive ≥4 units of red cells. Women receiving ≥4 units in tertiary settings were more likely to receive other blood products and have longer hospital stays, but morbidity, readmission and hysterectomy rates were similar.Although 46% of women had no identifiable risk factors early in pregnancy, 20% of transfusions of ≥4 units occurred within this group. By the birth admission 70% of women had at least one risk factor for requiring ≥4 units of red cells.ConclusionsOverall outcomes for women receiving ≥4 units of red cells were comparable between tertiary and non-tertiary facilities. This is important given the inability of known risk factors to predict many instances of postpartum haemorrhage.

The impact of blood type on the mortality of patients with severe abdominal trauma: a multicenter observational study

Few studies have investigated the relationship between blood type and trauma outcomes according to the type of injury. We conducted a retrospective multicenter observational study in twelve emergency hospitals in Japan. Patients with isolated severe abdominal injury (abbreviated injury scale for the abdomen ≥ 3 and that for other organs < 3) that occurred between 2008 and 2018 were divided into four groups according to blood type. The association between blood type and mortality, ventilator-free days (VFD), and total transfusion volume were evaluated using univariate and multivariate regression models. A total of 920 patients were included, and were divided based on their blood type: O, 288 (31%); A, 345 (38%); B, 186 (20%); and AB, 101 (11%). Patients with type O had a higher in-hospital mortality rate than those of other blood types (22% vs. 13%, p < 0.001). This association was observed in multivariate analysis (adjusted odds ratio [95% confidence interval] = 1.48 [1.25–2.26], p = 0.012). Furthermore, type O was associated with significantly higher cause-specific mortalities, fewer VFD, and larger transfusion volumes. Blood type O was associated with significantly higher mortality and larger transfusion volumes in patients with isolated severe abdominal trauma.

Neonatal and pediatric blood bank practice in the United States: Results from the AABB pediatric transfusion medicine subsection survey.

There are limited standards guiding the selection and processing of blood components specific for neonatal and pediatric transfusions. Therefore, blood banks (BBs) and transfusion services must create their own policies and procedures. The American Association of Blood Banks (AABB) Pediatric Transfusion Medicine Subsection Committee developed a 74-question survey to capture neonatal and pediatric BB practices in the United States. Thirty-five centers completed the survey: a response rate 15.8%. Responses indicated that most carry a mixed inventory of red blood cells (RBCs); 94.2% allow more than one type of RBC product for small-volume (SV) and large-volume (LV) transfusions to neonatal and pediatric patients. Many had storage age thresholds for RBCs transfused to neonates (SV=60%, LV=67.7%) but not older pediatric patients. The use of Group O for nonurgent RBC transfusion in neonates was common (74.2%). Responses related to special processing of RBCs and platelets indicated that 100% RBC and platelets are leukocyte-reduced (LR) for neonates and 97% for non-neonates. Irradiation of RBCs and platelets was commonly performed for neonatal transfusion (88.6%). Providing cytomegalovirus (CMV) seronegative products, volume reduction, and washing were variable. All centers transfused single-donor apheresis platelets; 20% allowed pathogen reduction (PR). The majority of centers have strategies limiting the amount of incompatible plasma transfused; however, few titrate ABO isoagglutinins in plasma-containing products (20% for platelets and 9.1% for plasma). Variability exists in BB practice for neonatal and pediatric transfusion. Future studies are needed to understand and define best BB practices in these patient populations.

Science, Medicine, and the Anesthesiologist

Science, Medicine, and the Anesthesiologist

Familial pseudohyperkalemia induces significantly higher levels of extracellular potassium in early storage of red cell concentrates without affecting other standard measures of quality: A case control and allele frequency study

Familial pseudohyperkalemia (FP) is characterized by an increased rate of potassium leakage in refrigerated red cells and is associated with the minor allele of the single nucleotide polymorphism rs148211042 (R723Q) in the ABCB6 gene. The study aims were to obtain the minor allele frequencies of ABCB6 variants and to measure supernatant potassium accumulation, and other red cell storage parameters, in red cell concentrates (RCC) from carriers of variant rs148211042 under standard blood bank conditions. Whole blood units were collected from 6 FP individuals and 11 controls and processed into RCC in additive solution. RCC were sampled and tested over cold storage for full blood count, extracellular potassium, glucose, lactate, microvesicle release, deformability, hemolysis, pH, adenosine triphosphate, and 2,3-diphosphoglycerate. Screening of genotyped cohorts identified that variant rs148211042 is present in 1 in 394 British citizens of European ancestry. FP RCC had significantly higher supernatant potassium at all time points from day 3 onwards (p < .001) and higher mean cell volume (p=.032) than controls. The initial rate of potassium release was higher in FP RCC; supernatant potassium reached 46.0 (23.8-57.6) mmol/L (mean [range]) by day 5, increasing to 68.9 (58.8-73.7) mmol/L by day 35. Other quality parameters were not significantly different between FP RCC and controls. These data suggest that if a blood donor has FP, reducing the RCC shelf-life to 5 days may be insufficient to reduce the risk of hyperkalemia in clinical scenarios such as neonatal large volume transfusion.

Hemodynamics of different volumes of red blood cell transfusion in preterm infants.

Although many controversies exist regarding the risk of red blood cell (RBC) transfusions, half of preterm infants born at <32weeks of gestational age receive such transfusions because of anemia of prematurity. Because of the costs and risks associated with multiple transfusions, it has been suggested that a large transfusion volume reduces the number of transfusions. However, there have been persistent concerns that RBC transfusion might lead to volume overload. We examined the impacts of large (20mL/kg) compared to standard volume (15mL/kg) transfusions on the hemodynamic variables of stable, electively transfused, preterm infants, by serially measuring echocardiographic parameters and plasma B-type natriuretic peptide levels. A total of 39 infants born at <34weeks of gestation and aged >2weeks at the time of enrollment were randomly allocated to either a standard volume (15mL/kg) or a large volume (20mL/kg) group. Significant reductions in cardiac output and transient increases in plasma B-type natriuretic peptide levels were found after RBC transfusion in both the standard and large volume (20mL/kg) groups. However, these changes were not significantly different between the two groups. Large-volume transfusions could be tolerable in stable preterm infants with anemia.

Trigger and Target for Fibrinogen Supplementation Using Thromboelastometry (ROTEM) in Patients Undergoing Open Thoraco-Abdominal Aortic Aneurysm Repair

To determine the relationship between the value of fibrinogen assessed by the FIBTEM clot amplitude at 10 minutes (A10 FIBTEM) measured on admission to the intensive care unit (ICU) and the amount of drainage output at 24 hours, to investigate whether the A10 FIBTEM predicts severe bleeding (SB), and to define A10 FIBTEM thresholds to prevent (trigger) and treat (target) severe bleeding by fibrinogen supplementation. In a single centre, retrospective observational study, 166 patients underwent elective open thoraco-abdominal aortic aneurysm (TAAA) repair between March 2016 and January 2019. Exclusion criteria were emergency, congenital, or acquired coagulopathy, or administration of P2Y12 inhibitor antiplatelet agents in the five days before surgery. All patients were managed intra-operatively and post-operatively according to a rotational thromboelastometry driven transfusion protocol. The principal endpoint was a composite outcome, which included bleeding, large volume transfusion, and re-operation. FIBTEM clot amplitude after 10 minutes measured on ICU admission and post-operative bleeding at 24 hours showed an inverse linear relationship (R2= .03; p= .026). Performance of A10 FIBTEM in predicting SB evaluated by Receiving Operating Curve analysis showed an area under the curve of 0.63 (95% CI 0.56 - 0.70; p= .026) with a best cutoff of 9 mm. An A10 FIBTEM of 3 mm was the cutoff associated with a positive predictive value of 50%, while an A10 FIBTEM of 9 mm showed a negative predictive value of 92%. On multivariable analysis, an A10 FIBTEM ≤ 3 mm remained independently associated with SB. The present investigation shows for the first time in a population undergoing open TAAA repair that an A10 FIBTEM ≤ 3mm on ICU admission is associated with post-operative severe bleeding. Trigger and target values for fibrinogen supplementation, based on A10 FIBTEM, have been provided. The transferability and reliability of these cutoff values require further study.

Association of Cryoprecipitate Use With Survival After Major Trauma in Children Receiving Massive Transfusion

Although most massive transfusion protocols incorporate cryoprecipitate in the treatment of hemorrhaging injured patients, minimal data exist on its use in children, and whether its addition improves their survival is unclear. To determine whether cryoprecipitate use for injured children who receive massive transfusion is associated with lower mortality. This retrospective cohort study included injured patients examined between January 1, 2014, and December 31, 2017, at one of multiple centers across the US and Canada participating in the Pediatric Trauma Quality Improvement Program. Patients were aged 18 years or younger and had received massive transfusion, which was defined as at least 40 mL/kg of total blood products in the first 4 hours after emergency department arrival. Exclusion criteria included hospital transfer, arrival without signs of life, time of death or hospital discharge not recorded, and isolated head injuries. To adjust for potential confounding, a propensity score for treatment was created and inverse probability weighting was applied. The propensity score accounted for age, sex, race/ethnicity, injury type, payment type, Glasgow Coma Scale score, hypoxia, hypotension, assisted respirations, chest tube status, Injury Severity Score, total volume of blood products received, hemorrhage control procedure, hospital size, academic status, and trauma center designation. Data were analyzed from December 11, 2019, to August 31, 2020. Cryoprecipitate use within the first 4 hours of emergency department arrival. In-hospital 24-hour and 7-day mortality. Of the 2387 injured patients who received massive transfusion, 1948 patients were eligible for analysis. The median age was 16 years (interquartile range, 9-17 years), 1382 patients (70.9%) were male, and 807 (41.4%) were White. A total of 541 patients (27.8%) received cryoprecipitate. After propensity score weighting, patients who received cryoprecipitate had a significantly lower 24-hour mortality when compared with those who did not (adjusted difference, -6.9%; 95% CI, -10.6% to -3.2%). Moreover, cryoprecipitate use was associated with a significantly lower 7-day mortality but only in children with penetrating trauma (adjusted difference, -9.2%; 95% CI, -15.4% to -3.0%) and those transfused at least 100 mL/kg of total blood products (adjusted difference, -7.7%; 95% CI, -15.0% to -0.5%). In this cohort study, early use of cryoprecipitate was associated with lower 24-hour mortality among injured children who required massive transfusion. The benefit of cryoprecipitate appeared to persist for 7 days only in those with penetrating trauma and in those who received extremely large-volume transfusion.

Potential Consequences of the Red Blood Cell Storage Lesion on Cardiac Electrophysiology.

BackgroundThe red blood cell (RBC) storage lesion is a series of morphological, functional, and metabolic changes that RBCs undergo following collection, processing, and refrigerated storage for clinical use. Since the biochemical attributes of the RBC unit shifts with time, transfusion of older blood products may contribute to cardiac complications, including hyperkalemia and cardiac arrest. We measured the direct effect of storage age on cardiac electrophysiology and compared it with hyperkalemia, a prominent biomarker of storage lesion severity.Methods and ResultsDonor RBCs were processed using standard blood‐banking techniques. The supernatant was collected from RBC units, 7 to 50 days after donor collection, for evaluation using Langendorff‐heart preparations (rat) or human induced pluripotent stem cell–derived cardiomyocytes. Cardiac parameters remained stable following exposure to “fresh” supernatant from red blood cell units (day 7: 5.8±0.2 mM K+), but older blood products (day 40: 9.3±0.3 mM K+) caused bradycardia (baseline: 279±5 versus day 40: 216±18 beats per minute), delayed sinus node recovery (baseline: 243±8 versus day 40: 354±23 ms), and increased the effective refractory period of the atrioventricular node (baseline: 77±2 versus day 40: 93±7 ms) and ventricle (baseline: 50±3 versus day 40: 98±10 ms) in perfused hearts. Beating rate was also slowed in human induced pluripotent stem cell–derived cardiomyocytes after exposure to older supernatant from red blood cell units (−75±9%, day 40 versus control). Similar effects on automaticity and electrical conduction were observed with hyperkalemia (10–12 mM K+).ConclusionsThis is the first study to demonstrate that “older” blood products directly impact cardiac electrophysiology, using experimental models. These effects are likely caused by biochemical alterations in the supernatant from red blood cell units that occur over time, including, but not limited to hyperkalemia. Patients receiving large volume and/or rapid transfusions may be sensitive to these effects.

The Association of Increased FFP:RBC Transfusion Ratio to Primary Graft Dysfunction in Bleeding Lung Transplantation Patients

Lung transplantation is associated with a significant risk of needed transfusion. Although algorithm-based transfusion strategies that promote a high fresh frozen plasma:red blood cells (FFP:RBC) ratio have reduced overall blood product requirements in other populations, large-volume transfusions have been linked to primary graft dysfunction (PGD) in lung transplantation, particularly use of platelets and plasma. The authors hypothesized that in lung transplant recipients requiring large-volume transfusions, a higher FFP:RBC ratio would be associated with increased PGD severity at 72 hours. Observational retrospective review. Single tertiary academic center. Adult patients undergoing bilateral or single orthotopic lung transplantation and receiving >4 U PRBC in the first 72 hours from February 2014 to March 2019. None. Patient demographics, operative characteristics, blood transfusions, and outcomes including PGD scores and length of stay were collected. Eighty-nine patients received >4U PRBC, had available 72-hour PGD data, and were included in the study. These patients were grouped into a high-ratio (>1:2 units of FFP:RBC, N = 38) or low-ratio group (<1:2 units of FFP:RBC, N = 51). Patients in the high-ratio group received more transfusions and factor concentrates and had significantly longer case length. The high-ratio group had a higher rate of severe PGD at 72 hours (60.5% v 23.5%, p = 0.0013) and longer hospital length of stay (40 v 32 days, p = 0.0273). In bleeding lung transplantation patients at high risk for PGD, a high FFP:RBC transfusion ratio was associated with worsened 72-hour PGD scores when compared with the low-ratio cohort.