Recombinant ADAMTS13 for Immune Thrombotic Thrombocytopenic Purpura.

In patients with immune thrombotic thrombocytopenic purpura (iTTP), autoantibodies against the metalloprotease ADAMTS13 lead to catastrophic microvascular thrombosis. However, the potential benefits of recombinant human ADAMTS13 (rADAMTS13) in patients with iTTP remain unknown. Here, we report the clinical use of rADAMTS13, which resulted in the rapid suppression of disease activity and complete recovery in a critically ill patient whose condition had proved to be refractory to all available treatments. We also show that rADAMTS13 causes immune complex formation, which saturates the autoantibody and may promote its clearance. Our data support the role of rADAMTS13 as a novel adjunctive therapy in patients with iTTP.

Low-frequency inherited complement receptor variants are associated with purpura fulminans.

ABSTRACT: Extreme disease phenotypes can provide key insights into the pathophysiology of common conditions, but studying such cases is challenging due to their rarity and the limited statistical power of existing methods. Herein, we used a novel approach to pathway-based mutational burden testing, the rare variant trend test (RVTT), to investigate genetic risk factors for an extreme form of sepsis-induced coagulopathy, infectious purpura fulminans (PF). In addition to prospective patient sample collection, we electronically screened over 10.4 million medical records from 4 large hospital systems and identified historical cases of PF for which archived specimens were available to perform germline whole-exome sequencing. We found a significantly increased burden of low-frequency, putatively function-altering variants in the complement system in patients with PF compared with unselected patients with sepsis (P = .01). A multivariable logistic regression analysis found that the number of complement system variants per patient was independently associated with PF after controlling for age, sex, and disease acuity (P = .01). Functional characterization of PF-associated variants in the immunomodulatory complement receptors CR3 and CR4 revealed that they result in partial or complete loss of anti-inflammatory CR3 function and/or gain of proinflammatory CR4 function. Taken together, these findings suggest that inherited defects in CR3 and CR4 predispose to the maladaptive hyperinflammation that characterizes severe sepsis with coagulopathy.

Donor-derived disorders of hemostasis and thrombosis in liver transplantation: Considerations for deceased donor liver selection.

OLT is known to be associated with a precarious perioperative hemostatic state due to dysregulation of procoagulant and anticoagulant factors, endothelial injury, and inflammation. Transmission of inherited bleeding and clotting disorders from the liver donor to the recipient may further complicate hemostasis during and after transplantation. As a result, consideration of congenital coagulation disorders in the liver donor is a practical concern for donor selection. However, there is no clear consensus regarding the selection of donors with known or suspected thrombophilia or bleeding disorders. While multiple case reports and retrospective studies, subject to reporting bias, describe donor-derived thrombophilic and bleeding disorders, there are no large-scale studies in the adult liver transplant literature that examine the frequency of transmission, utility of donor screening, or clinical impact of donor hemostatic disorders. Based on the reported literature, we summarize our approach for donor selection with an aim to balance improved organ utility and optimal post-transplant outcomes.

Emergency transfusion with whole blood versus packed red blood cells: A study of 1400 patients.

BACKGROUND: Low-titer group O whole blood (LTOWB) is increasingly used for emergency transfusion. We studied whether initial release of LTOWB compared with packed red blood cells (pRBCs) reduced overall blood requirements for patients needing emergency transfusion. Secondary outcomes examined included survival and non-lethal adverse clinical outcomes. STUDY DESIGN AND METHODS: A retrospective, single-center, before-versus-after study compared patients transfused with emergency-release, uncrossmatched pRBC followed by component therapy (2016-2019) versus patients transfused with emergency-release, uncrossmatched LTOWB followed by component therapy (2019-2022). RESULTS: Outcomes were available for 602 patients in the pRBC group versus 749 in the whole blood group. The two groups were similar for age, sex, race, estimated blood volume, ABO blood groups, and underlying diagnosis. Use of LTOWB was associated with increased blood product use at 24 h (4.0 (2.0-12.0) in pRBC group versus 6.5 (4.2-12.7) in LTOWB group, p < .0001) and at 7 days (5.5 (3.0-13.0) in pRBC group versus 7.3 (4.3-14.3) in LTOWB group, p < .0001). Initial use of LTOWB was not associated with improved 24 h or 30 day survival nor lower incidence of non-lethal adverse clinical outcomes compared with pRBC. DISCUSSION: Our study showed a statistically significant increase in total blood use and blood acquisition costs for patients receiving initial emergency transfusion with LTOWB compared with pRBC. The initial use of LTOWB offered no advantage over component therapy for 30 day survival or selected non-lethal adverse outcomes.

COVID-19 and coagulation: bleeding and thrombotic manifestations of SARS-CoV-2 infection.

Patients with coronavirus disease 2019 (COVID-19) have elevated D-dimer levels. Early reports describe high venous thromboembolism (VTE) and disseminated intravascular coagulation (DIC) rates, but data are limited. This multicenter retrospective study describes the rate and severity of hemostatic and thrombotic complications of 400 hospital-admitted COVID-19 patients (144 critically ill) primarily receiving standard-dose prophylactic anticoagulation. Coagulation and inflammatory parameters were compared between patients with and without coagulation-associated complications. Multivariable logistic models examined the utility of these markers in predicting coagulation-associated complications, critical illness, and death. The radiographically confirmed VTE rate was 4.8% (95% confidence interval [CI], 2.9-7.3), and the overall thrombotic complication rate was 9.5% (95% CI, 6.8-12.8). The overall and major bleeding rates were 4.8% (95% CI, 2.9-7.3) and 2.3% (95% CI, 1.0-4.2), respectively. In the critically ill, radiographically confirmed VTE and major bleeding rates were 7.6% (95% CI, 3.9-13.3) and 5.6% (95% CI, 2.4-10.7), respectively. Elevated D-dimer at initial presentation was predictive of coagulation-associated complications during hospitalization (D-dimer >2500 ng/mL, adjusted odds ratio [OR] for thrombosis, 6.79 [95% CI, 2.39-19.30]; adjusted OR for bleeding, 3.56 [95% CI, 1.01-12.66]), critical illness, and death. Additional markers at initial presentation predictive of thrombosis during hospitalization included platelet count >450 × 109/L (adjusted OR, 3.56 [95% CI, 1.27-9.97]), C-reactive protein (CRP) >100 mg/L (adjusted OR, 2.71 [95% CI, 1.26-5.86]), and erythrocyte sedimentation rate (ESR) >40 mm/h (adjusted OR, 2.64 [95% CI, 1.07-6.51]). ESR, CRP, fibrinogen, ferritin, and procalcitonin were higher in patients with thrombotic complications than in those without. DIC, clinically relevant thrombocytopenia, and reduced fibrinogen were rare and were associated with significant bleeding manifestations. Given the observed bleeding rates, randomized trials are needed to determine any potential benefit of intensified anticoagulant prophylaxis in COVID-19 patients.

A cross-sectional study of haemolytic disease of the newborn in Uganda.

BACKGROUND AND OBJECTIVES: Haemolytic disease of the newborn (HDN) is an immune haemolytic anaemia from maternal alloantibodies. Rh immunoglobulin (RhIg) prophylaxis can prevent alloimmunization to the D antigen. However, RhIg is not universally available in Uganda. ABO incompatibility also causes HDN. We determined the prevalence of HDN among newborn infants with jaundice in Uganda. MATERIALS AND METHODS: We conducted a prospective cross-sectional study at Kawempe National Referral Hospital, Kampala, Uganda. Infants aged 0-14 days with neonatal jaundice (or total bilirubin >50 µmol/L) were enrolled. Clinical evaluation and laboratory testing, including ABO, RhD typing and maternal antibody screen, were performed. RESULTS: A total of 466 babies were enrolled. The mean (SD) age was 3.4 (1.5) days. Of newborn babies with jaundice, 17.2% (80/466) had HDN. Babies with HDN had lower haemoglobin (SD); 15.7 (2.7) compared with those without HDN; 16.4 (2.4) g/dL, p = 0.016; and a higher bilirubin (interquartile range); 241 (200-318) compared with those without HDN; 219 (191-263) µmol/L, p < 0.001. One baby had anti-D HDN, while 46/466 had HDN from an ABO incompatibility (anti-A 43.5% and anti-B 56.5%); 82% of babies with HDN also had suspected neonatal sepsis or birth asphyxia. About 79.2% (57/72) of mothers did not have ABO/Rh blood group performed antenatally. All infants with HDN survived except one. CONCLUSION: Among newborn infants with jaundice, HDN is not rare. The majority is due to ABO HDN affecting group A and group B babies equally. Ensuring routine ABO/Rh grouping for all pregnant women is an area for improvement.

Multiorgan failure in a fatal case of autoimmune hemolytic anemia.

BACKGROUND: Autoimmune hemolytic anemia (AIHA) results in red blood cell destruction by auto-antibodies directed against surface antigens and is rarely fatal. Here we describe a case of AIHA, refractory to both standard and experimental therapies, complicated by multiorgan failure, and rapidly leading to death. CASE REPORT AND RESULTS: A 65 year-old man who presented with progressive dyspnea and jaundice was found to have hemolytic anemia. Diagnostic work-up revealed a positive direct antiglobulin test and a strong pan-reactive antibody in the plasma reacting to a titer of 1:1024 with strongest reactivity at 37 °C Coombs' phase with reagent anti-IgG. The red cell eluate contained a pan-agglutinin. The patient received multiple lines of treatment including glucocorticoids, intravenous immunoglobulin, rituximab, eculizumab, splenectomy and etoposide. Despite these interventions, he continued to experience brisk hemolysis and remained transfusion dependent. Repeat testing on day 16 demonstrated persistent high titer IgG auto-antibodies, suggesting minimal suppressive effect of therapy. His course was complicated by acute renal and liver failure, venous thrombosis, and worsening coagulopathy, and he ultimately died from multiorgan failure on day 18. CONCLUSION: Severe cases of AIHA can result in multiorgan failure and a fatal outcome. The rapid development of liver failure in this setting has been described in only few case reports to date, and represents an important complication for clinicians to be aware of when treating patients with AIHA.

Deaths and complications associated with the management of acute immune thrombotic thrombocytopenic purpura.

BACKGROUND: The introduction of therapeutic plasma exchange (TPE) dramatically decreased mortality in patients with immune thrombotic thrombocytopenic purpura (iTTP). However, there are few modern descriptions of residual causes of death from iTTP and complications associated with TPE. STUDY DESIGN AND METHODS: This was a retrospective study in a multi-institutional cohort of 109 patients with iTTP between 2004 and 2017. Complications of TPE were analyzed in a subset of this cohort (74 patients representing 101 treatment courses). RESULTS: Death occurred in 8 of 109 patients (7.3%) and in 8 of 219 captured episodes of acute iTTP (mortality rate per episode: 3.7%). Neither the number of TPE treatments nor length of hospitalization predicted mortality. The majority of deaths (5/8) were associated with delay in the diagnosis of iTTP or initiation of TPE or presentation to the hospital in a moribund state. A subset of patients (N = 74) was analyzed for TPE-related complications. Most patients (56/74; 76%) had at least one minor or major complication of TPE. Seven of 101 (6.9%) discrete treatment courses were associated with one or more severe complications, including anaphylaxis and line-associated infections and thrombosis. Overall, the most frequent adverse events were mild allergic (urticarial) transfusion reactions, which affected 34 of 101 (34%) treatment courses. One patient died from a TPE-related complication, line-associated bacteremia. CONCLUSION: Early identification of patients with iTTP and the rapid initiation of TPE are paramount in preventing mortality. While TPE was associated with a high rate of adverse events, the vast majority were treatable and TPE-related mortality is low.

Improving Transfusion Safety in the Operating Room With a Barcode Scanning System Designed Specifically for the Surgical Environment and Existing Electronic Medical Record Systems: An Interrupted Time Series Analysis.

BACKGROUND: Manual processes for verifying patient identification before blood transfusion and documenting this pretransfusion safety check are prone to errors, and compliance with manual systems is especially poor in urgent operating room settings. An automated, electronic barcode scanner system would be expected to improve pretransfusion verification and documentation. METHODS: Audits were conducted of blood transfusion documentation under a manual paper system from January to October 2014. An electronic barcode scanning system was developed to streamline transfusion safety checking and automate documentation. This system was implemented in 58 operating rooms between October and December 2014, with follow-up compliance audits through December 2015. The association of barcode scanner implementation with transfusion documentation compliance was assessed using an interrupted time series analysis. Anesthesia providers were surveyed regarding their opinions on the electronic system. In mid-2016, the scanning system was modified to transfer from the Metavision medical record system to Epic OpTime. Follow-up analysis assessed performance of this system within Epic during 2017. RESULTS: In an interrupted time series analysis, the proportion of units with compliant documentation was estimated to be 19.6% (95% confidence interval [CI], 10.7-25.6) the week before scanner implementation, and 74.4% (95% CI, 59.4-87.4) the week after implementation. There was a significant postintervention level change (odds ratio 10.80, 95% CI, 6.31-18.70; P < .001) and increase in slope (odds ratio 1.14 per 1-week increase, 95% CI, 1.11-1.17; P < .001). After implementation, providers chose to use the new electronic system for 98% of transfusions. Across the 2 years analyzed (15,997 transfusions), the electronic system detected 45 potential transfusion errors in 27 unique patients, and averted transfusion of 36 mismatched blood products into 20 unique patients. A total of 69%, 86%, and 88% of providers reported the electronic system improved patient safety, blood transfusion workflow, and transfusion documentation, respectively. When providers used the barcode scanner, no transfusion errors or reactions were reported. The scanner system was successfully transferred from Metavision to Epic without retraining staff or changing workflows. CONCLUSIONS: A barcode-based system designed for easy integration to different commonly used anesthesia information management systems was implemented in a large urban academic hospital. The system allows a single user with the assistance of a software system to perform and document pretransfusion safety verification. The system improved transfusion documentation compliance, averted potential transfusion errors, and became the preferred method of blood transfusion safety checking.

Electronic patient identification for sample labeling reduces wrong blood in tube errors.

BACKGROUND: Wrong blood in tube (WBIT) errors are a preventable cause of ABO-mismatched RBC transfusions. Electronic patient identification systems (e.g., scanning a patient's wristband barcode before pretransfusion sample collection) are thought to reduce WBIT errors, but the effectiveness of these systems is unclear. STUDY DESIGN AND METHODS: Part 1: Using retrospective data, we compared pretransfusion sample WBIT rates at hospitals using manual patient identification (n = 16 sites; >1.6 million samples) with WBIT rates at hospitals using electronic patient identification for some or all sample collections (n = 4 sites; >0.5 million samples). Also, we compared WBIT rates after implementation of electronic patient identification with preimplementation WBIT rates. Causes and frequencies of WBIT errors were evaluated at each site. Part 2: Transfusion service laboratories (n = 18) prospectively typed mislabeled (rejected) samples (n = 2844) to determine WBIT rates among samples with minor labeling errors. RESULTS: Part 1: The overall unadjusted WBIT rate at sites using manual patient identification was 1:10,110 versus 1:35,806 for sites using electronic identification (p < 0.0001). Correcting for repeat samples and silent WBIT errors yielded overall adjusted WBIT rates of 1:3046 for sites using manual identification and 1:14,606 for sites using electronic identification (p < 0.0001), with wide variation among individual sites. Part 2: The unadjusted WBIT rate among mislabeled (rejected) samples was 1:71 (adjusted WBIT rate, 1:28). CONCLUSION: In this study, using electronic patient identification at the time of pretransfusion sample collection was associated with approximately fivefold fewer WBIT errors compared with using manual patient identification. WBIT rates were high among mislabeled (rejected) samples, confirming that rejecting samples with even minor labeling errors helps mitigate the risk of ABO-incompatible transfusions.

Risk factors for recurrent severe anemia among previously transfused children in Uganda: an age-matched case-control study.

BACKGROUND: In resource-poor settings, transfused children often experience recurrence of severe anemia (SA) following discharge from hospital. This study determined the factors associated with recurrent severe anemia (RSA) among previously transfused Ugandan children aged less than 5 years. METHODS: A case-control study was conducted in five hospitals in Uganda from March 2017 to September 2018. We prospectively enrolled 196 hospitalised children who had been transfused for severe anemia 2 weeks to 6 months prior to enrollment. Of these, 101 children (cases) were re-admitted with a hemoglobin [Hb] level of ≤6 g/dL and required transfusion; and 95 children (age-matched controls) were admitted for other clinical illness with a Hb > 6 g/dL. Children known to have sickle cell anemia, cancer, or bleeding disorders were excluded. Clinical and laboratory evaluation were done. Conditional logistic regression adjusted for age, was used to determine factors associated with RSA. RESULTS: The median time (IQR) between the earlier transfusion and enrollment was 3.5 (1.9-5.7) months for cases, and was 5.0 (2.9-6.0) months for controls (p-value = 0.015). Risk factors (adjusted odds ratio, 95% confidence interval, and significance) for development of RSA were: hemoglobinuria (36.33, 2.19-600.66, p = 0.012); sickle cell anemia - newly diagnosed (20.26, 2.33-176.37, p = 0.006); history of earlier previous transfusions (6.95, 1.36-35.61, p = 0.020) and malaria infection (6.47, 1.17-35.70, p = 0.032). CONCLUSION: Malaria chemoprevention, follow up visit for Hb check after discharge from hospital and sickle cell screening among previously transfused children represent practical strategies to prevent and identify children at risk for recurrent severe anemia. The cause of hemoglobinuria in children merits further investigations.

Reduction in Operating Room Plasma Waste After Evidence-Based Quality Improvement Initiative.

Anesthesiologists request units of plasma in anticipation of transfusion. The amount of plasma transfused intraoperatively is less than that issued (requested, thawed, and sent). We presented institutional-specific data on plasma usage including anesthesiologist-specific ratios of plasma issued-to-transfused. In month-to-month comparisons from the year before the presentation (June-December 2015) to 7 months after (June-December 2016), plasma issued to the operating room was reduced from 434.9 ± 81 to 327.3 ± 65 units, a change of 107.6 units per month (95% confidence interval [CI], 22-193); plasma discarded by the blood bank was reduced from 109.7 ± 48 units to 69.1 ± 9 units, a change of 40.6 units per month (95% CI, 0.2-81); and plasma transfused went from 188.4 ± 42 units to 160.7 ± 52 units, a nonsignificant change of 27.7 units per month (95% CI, -27 to 83).

B-type natriuretic peptide and plasma hemoglobin levels following transfusion of shorter-storage versus longer-storage red blood cells: Results from the TOTAL randomized trial.

BACKGROUND: Prior studies have suggested that transfusion of stored red blood cells (RBCs) with increased levels of cell-free hemoglobin might reduce the bioavailability of recipient nitric oxide (NO) and cause myocardial strain. METHODS: Ugandan children (ages 6-60 months) with severe anemia and lactic acidosis were randomly assigned to receive RBCs stored 1-10 days versus 25-35 days. B-type natriuretic peptide (BNP), vital signs, renal function test results, and plasma hemoglobin were measured. Most children had either malaria or sickle cell disease and were thus at risk for reduced NO bioavailability. RESULTS: Seventy patients received RBCs stored 1-10 days, and 77 received RBCs stored 25-35 days. The median (interquartile range) cell-free hemoglobin was nearly 3 times higher in longer-storage RBCs (26.4 [15.5-43.4] µmol/L) than in shorter-storage RBCs (10.8 [7.8-18.6] µmol/L), P < .0001. Median (interquartile range) BNP 2 hours posttransfusion was 156 (59-650) pg/mL (shorter storage) versus 158 (59-425) pg/mL (longer storage), P = .76. BNP values 22 hours posttransfusion were 110 (46-337) pg/mL (shorter storage) versus 96 (49-310) pg/mL (longer storage), P = .76. Changes in BNP within individuals from pretransfusion to 2 hours (or 22 hours) posttransfusion were not significantly different between the study groups. BNP change following transfusion did not correlate with the concentration of cell-free hemoglobin in the RBC supernatant. Blood pressure, blood urea nitrogen, creatinine, and change in plasma hemoglobin were not significantly different in the 2 groups. CONCLUSION: In a randomized trial among children at risk for reduced NO bioavailability, we found that BNP, blood pressure, creatinine, and plasma hemoglobin were not higher in patients receiving RBCs stored for 25-35 versus 1-10 days.

Fresh-Frozen Plasma: Ordering Patterns and Utilization in the Operating Rooms of a Tertiary Referral Hospital.

BACKGROUND: Blood product transfusion is the most commonly performed hospital procedure. Intraoperative blood product utilization varies between institutions and anesthesiologists. In the United States in 2011, nearly 4 million plasma units were transfused. METHODS: A retrospective analysis of intraoperative plasma ordering patterns and utilization (thawing and transfusing) was performed at a tertiary, academic hospital between January 2015 and March 2016. RESULTS: Over 15 months, 46,002 operative procedures were performed. In 1540 of them, plasma was thawed or transfused: 8297 plasma units were thawed and 3306 of those units were transfused. These 3306 plasma units were transfused in 749 cases with a median of 2 plasma units (interquartile range, 2-4) transfused. The percentage of average monthly procedures with plasma thawed and none transfused was 51.3% (confidence interval, 49.0%-53.6%). The cardiac surgery service requested the greatest number of plasma units to be thawed (2143) but only transfused 712 (33.2%) of them. Of all plasma units not transfused, 45% were generated by procedures with 1 to 4 units of plasma thawed; 95.7% of these units were thawed as even integers (ie, 2, 4). CONCLUSIONS: For operative procedures, far more plasma was thawed than was transfused and this practice occurred across surgical specialties and anesthesiologists. Considering the plasma that was not transfused, 45% occurred in procedures with 4 or fewer units of plasma requested suggesting these low-volume requests were a primary source of potential waste. Further studies are needed to examine associations between plasma utilization and clinical outcomes.

Innocent lives lost and saved: the importance of blood transfusion for children in sub-Saharan Africa.

Severe anemia in children is a leading indication for blood transfusion worldwide. Severe anemia, defined by the World Health Organization as a hemoglobin level <5 g/dL, is particularly common throughout sub-Saharan Africa. Analysis of data from the Fluid Expansion as Supportive Therapy (FEAST) trial offers new insights into the importance of blood transfusion for children with severe anemia. The principal findings of this analysis include the observations that life-threatening anemia in children is a frequent presenting condition in East Africa; that delays in transfusion therapy are lethal; and that inadequate transfusion is probably more common than currently recognized. The findings of this new study highlight the need for changes in blood inventory management in sub-Saharan hospitals and the need for more research on transfusion therapy for children in peril.

2015 proceedings of the National Heart, Lung, and Blood Institute's State of the Science in Transfusion Medicine symposium.

On March 25 and 26, 2015, the National Heart, Lung, and Blood Institute sponsored a meeting on the State of the Science in Transfusion Medicine on the National Institutes of Health (NIH) campus in Bethesda, Maryland, which was attended by a diverse group of 330 registrants. The meeting's goal was to identify important research questions that could be answered in the next 5 to 10 years and which would have the potential to transform the clinical practice of transfusion medicine. These questions could be addressed by basic, translational, and/or clinical research studies and were focused on four areas: the three "classical" transfusion products (i.e., red blood cells, platelets, and plasma) and blood donor issues. Before the meeting, four working groups, one for each area, prepared five major questions for discussion along with a list of five to 10 additional questions for consideration. At the meeting itself, all of these questions, and others, were discussed in keynote lectures, small-group breakout sessions, and large-group sessions with open discourse involving all meeting attendees. In addition to the final lists of questions, provided herein, the meeting attendees identified multiple overarching, cross-cutting themes that addressed issues common to all four areas; the latter are also provided. It is anticipated that addressing these scientific priorities, with careful attention to the overarching themes, will inform funding priorities developed by the NIH and provide a solid research platform for transforming the future practice of transfusion medicine.

Effect of Transfusion of Red Blood Cells With Longer vs Shorter Storage Duration on Elevated Blood Lactate Levels in Children With Severe Anemia: The TOTAL Randomized Clinical Trial.

IMPORTANCE: Although millions of transfusions are given annually worldwide, the effect of red blood cell (RBC) unit storage duration on oxygen delivery is uncertain. OBJECTIVE: To determine if longer-storage RBC units are not inferior to shorter-storage RBC units for tissue oxygenation as measured by reduction in blood lactate levels and improvement in cerebral tissue oxygen saturation among children with severe anemia. DESIGN, SETTING, AND PARTICIPANTS: Randomized noninferiority trial of 290 children (aged 6-60 months), most with malaria or sickle cell disease, presenting February 2013 through May 2015 to a university-affiliated national referral hospital in Kampala, Uganda, with a hemoglobin level of 5 g/dL or lower and a lactate level of 5 mmol/L or higher. INTERVENTIONS: Patients were randomly assigned to receive RBC units stored 25 to 35 days (longer-storage group; n = 145) vs 1 to 10 days (shorter-storage group; n = 145). All units were leukoreduced prior to storage. All patients received 10 mL/kg of RBCs during hours 0 through 2 and, if indicated per protocol, an additional 10 mL/kg during hours 4 through 6. MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of patients with a lactate level of 3 mmol/L or lower at 8 hours using a margin of noninferiority equal to an absolute difference of 25%. Secondary measures included noninvasive cerebral tissue oxygen saturation during the first transfusion, clinical and laboratory changes up to 24 hours, and survival and health at 30 days after transfusion. Adverse events were monitored up to 24 hours. RESULTS: In the total population of 290 children, the mean (SD) presenting hemoglobin level was 3.7 g/dL (1.3) and mean lactate level was 9.3 mmol/L (3.4). Median (interquartile range) RBC unit storage was 8 days (7-9) for shorter storage vs 32 days (30-34) for longer storage without overlap. The proportion achieving the primary end point was 0.61 (95% CI, 0.52 to 0.69) in the longer-storage group vs 0.58 (95% CI, 0.49 to 0.66) in the shorter-storage group (between-group difference, 0.03 [95% CI, -0.07 to ∞], P < .001), meeting the prespecified margin of noninferiority. Mean lactate levels were not statistically different between the 2 groups at 0, 2, 4, 6, 8, or 24 hours. Kaplan-Meier analysis and global nonlinear regression revealed no statistical difference in lactate reduction between the 2 groups. Clinical assessment, cerebral oxygen saturation, electrolyte abnormalities, adverse events, survival, and 30-day recovery were also not significantly different between the groups. CONCLUSIONS AND RELEVANCE: Among children with lactic acidosis due to severe anemia, transfusion of longer-storage compared with shorter-storage RBC units did not result in inferior reduction of elevated blood lactate levels. These findings have relevance regarding the efficacy of stored RBC transfusion for patients with critical tissue hypoxia and lactic acidosis due to anemia. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01586923.

Anti-HLA alloantibodies in surgical patients refractory to platelet transfusion.

Alloimmune platelet refractoriness (alloPR) among actively bleeding surgical patients with thrombocytopenia represents a life-threatening problem. Here we present three cases in which surgical bleeding was complicated by life-threatening thrombocytopenia and alloPR. We demonstrate that the human leukocyte antigens (HLA) antibodies associated with alloPR are broadly reactive and in high concentration, are not removed by hemodilution, and are not absorbed by transfusion of multiple doses of platelet concentrates. HLA alloPR may be under-recognized among surgical patients. Research is needed to develop pre-operative screening methods that will identify patients in need of specialized platelet support using HLA compatible donor products.