Melissa M. Cushing

Effects of Red-Cell Storage Duration on Patients Undergoing Cardiac Surgery

BACKGROUND Some observational studies have reported that transfusion of red-cell units that have been stored for more than 2 to 3 weeks is associated with serious, even fatal, adverse events. Patients undergoing cardiac surgery may be especially vulnerable to the adverse effects of transfusion. METHODS We conducted a randomized trial at multiple sites from 2010 to 2014. Participants 12 years of age or older who were undergoing complex cardiac surgery and were likely to undergo transfusion of red cells were randomly assigned to receive leukocyte-reduced red cells stored for 10 days or less (shorter-term storage group) or for 21 days or more (longer-term storage group) for all intraoperative and postoperative transfusions. The primary outcome was the change in Multiple Organ Dysfunction Score (MODS; range, 0 to 24, with higher scores indicating more severe organ dysfunction) from the preoperative score to the highest composite score through day 7 or the time of death or discharge. RESULTS The median storage time of red-cell units provided to the 1098 participants who received red-cell transfusion was 7 days in the shorter-term storage group and 28 days in the longer-term storage group. The mean change in MODS was an increase of 8.5 and 8.7 points, respectively (95% confidence interval for the difference, -0.6 to 0.3; P=0.44). The 7-day mortality was 2.8% in the shorter-term storage group and 2.0% in the longer-term storage group (P=0.43); 28-day mortality was 4.4% and 5.3%, respectively (P=0.57). Adverse events did not differ significantly between groups except that hyperbilirubinemia was more common in the longer-term storage group. CONCLUSIONS The duration of red-cell storage was not associated with significant differences in the change in MODS. We did not find that the transfusion of red cells stored for 10 days or less was superior to the transfusion of red cells stored for 21 days or more among patients 12 years of age or older who were undergoing complex cardiac surgery. (Funded by the National Heart, Lung, and Blood Institute; RECESS ClinicalTrials.gov number, NCT00991341.).

Efficacy of transfusion with granulocytes from G-CSF/dexamethasone–treated donors in neutropenic patients with infection

High-dose granulocyte transfusion therapy has been available for 20 years, yet its clinical efficacy has never been conclusively demonstrated. We report here the results of RING (Resolving Infection in Neutropenia with Granulocytes), a multicenter randomized controlled trial designed to address this question. Eligible subjects were those with neutropenia (absolute neutrophil count <500/μL) and proven/probable/presumed infection. Subjects were randomized to receive either (1) standard antimicrobial therapy or (2) standard antimicrobial therapy plus daily granulocyte transfusions from donors stimulated with granulocyte colony-stimulating factor (G-CSF) and dexamethasone. The primary end point was a composite of survival plus microbial response, at 42 days after randomization. Microbial response was determined by a blinded adjudication panel. Fifty-six subjects were randomized to the granulocyte arm and 58 to the control arm. Transfused subjects received a median of 5 transfusions. Mean transfusion dose was 54.9 × 10(9) granulocytes. Overall success rates were 42% and 43% for the granulocyte and control groups, respectively (P > .99), and 49% and 41%, respectively, for subjects who received their assigned treatments (P = .64). Success rates for granulocyte and control arms did not differ within any infection type. In a post hoc analysis, subjects who received an average dose per transfusion of ≥0.6 × 10(9) granulocytes per kilogram tended to have better outcomes than those receiving a lower dose. In conclusion, there was no overall effect of granulocyte transfusion on the primary outcome, but because enrollment was half that planned, power to detect a true beneficial effect was low. RING was registered at www.clinicaltrials.gov as #NCT00627393.

Oxygen Therapeutics: Perfluorocarbons and Blood Substitute Safety

Current demands over the blood supply in developed and developing nations will compound over time. Red cell substitutes have a promising value proposition for transfusion services, because they hold the promise of increasing the availability of blood products and removing donor and contamination safety risks. In this article, the authors note that existing products suffer from critical shortcomings such as vasoactivity; they also point out that substitutes not based on human blood introduce potentially more complex safety hurdles. The authors discuss the attributes of an ideal blood substitute, and the mechanism and current status of perfluorocarbons; they also review the shortcomings of all oxygen therapeutic products in development today.

A comparison of adverse reaction rates for PAS C versus plasma platelet units.

Plasma constituents have been implicated in some types of platelet (PLT) transfusion reactions. Leukoreduced apheresis PLTs stored in InterSol have 65% less plasma than apheresis PLTs stored in 100% plasma (PPs). This study compared transfusion reaction rates in InterSol PLTs (PLT additive solution [PAS] C) versus PPs.

Oxygen therapeutics: pursuit of an alternative to the donor red blood cell.

CONTEXT There is no true substitute for the many functions of human red blood cells, and synthetic products will not replace the need for blood donation in the foreseeable future. Hemoglobin-based oxygen carriers have many characteristics that would serve as a useful adjunct to red cells in clinical settings. Over time, these technologies have the potential to dramatically reshape the practice of transfusion medicine. OBJECTIVE To review the characteristics and potential utility of hemoglobin-based oxygen carriers and perfluorocarbon-based oxygen carriers. Several hemoglobin-based oxygen carriers are under study in phase III clinical trials. Novel uses for synthetic oxygen therapeutics are emphasized. DATA SOURCES All published reports with the key words oxygen therapeutics, blood substitutes, and red cell substitutes from 1933 until March 2006 were searched through Medline. Significant findings were synthesized. CONCLUSIONS Recognition of the true impact of red cell substitutes is still several years away. The most compelling products, hemoglobin-based oxygen carriers, have potential use in trauma, providing immediate oxygen-carrying support in the face of alloantibodies or autoantibodies, and in other clinical situations in which long-term survival of red cells is not essential. In the interim, efforts should be focused on enhancing the current blood supply system while supporting ongoing and planned blood substitute research efforts, including trials assessing novel clinical indications for these products.

Cost-effectiveness of blood donor screening for Babesia microti in endemic regions of the United States.

Babesia microti is the leading reported cause of red blood cell (RBC) transfusion‐transmitted infection in the United States. Donor screening assays are in development.

Improved plasma removal efficiency for therapeutic plasma exchange using a new apheresis platform

BACKGROUND: The Spectra Optia (SPO; CaridianBCT) is a new apheresis device based on the COBE Spectra (CSP; CaridianBCT) platform. This study was designed to evaluate the safety and efficiency of the SPO in comparison to the predicate CSP device.

Reduced intensity haplo plus single cord transplant compared to double cord transplant: improved engraftment and graft-versus-host disease-free, relapse-free survival

Umbilical cord blood stem cell transplants are commonly used in adults lacking HLA-identical donors. Delays in hematopoietic recovery contribute to mortality and morbidity. To hasten recovery, we used co-infusion of progenitor cells from a partially matched related donor and from an umbilical cord blood graft (haplo-cord transplant). Here we compared the outcomes of haplo-cord and double-cord transplants. A total of 97 adults underwent reduced intensity conditioning followed by haplo-cord transplant and 193 patients received reduced intensity conditioning followed by double umbilical cord blood transplantation. Patients in the haplo-cord group were more often from minority groups and had more advanced malignancy. Haplo-cord recipients received fludarabine-melphalan-anti-thymocyte globulin. Double umbilical cord blood recipients received fludarabine-cyclophosphamide and low-dose total body irradiation. In a multivariate analysis, haplo-cord had faster neutrophil (HR=1.42, P=0.007) and platelet (HR=2.54, P<0.0001) recovery, lower risk of grade II–IV acute graft-versus-host disease (HR=0.26, P<0.0001) and chronic graft-versus-host disease (HR=0.06, P<0.0001). Haplo-cord was associated with decreased risk of relapse (HR 0.48, P=0.001). Graft-versus-host disease-free, relapse-free survival was superior with haplo-cord (HR 0.63, P=0.002) but not overall survival (HR=0.97, P=0.85). Haplo-cord transplantation using fludarabine-melphalan-thymoglobulin conditioning hastens hematopoietic recovery with a lower risk of relapse relative to double umbilical cord blood transplantation using the commonly used fludarabine-cyclophosphamide-low-dose total body irradiation conditioning. Graft-versus-host disease-free and relapse-free survival is significantly improved. Haplo-cord is a readily available graft source that improves outcomes and access to transplant for those lacking HLA-matched donors. Trials registered at clinicaltrials.gov identifiers 00943800 and 01810588.

Factor VIII/von Willebrand factor concentrate therapy for ventricular assist device–associated acquired von Willebrand disease

BACKGROUND: Acquired von Willebrand disease (aVWD) can lead to a propensity to bleed, and many different modalities have been used to treat this condition. The efficacy of these agents in patients with aVWD secondary to cardiac assist devices is not fully understood.

Determination of human platelet antigen typing by molecular methods: Importance in diagnosis and early treatment of neonatal alloimmune thrombocytopenia

Neonatal alloimmune thrombocytopenia (NAIT) is the most common cause of severe thrombocytopenia and intracranial hemorrhage in the perinatal period. While the gold standard for making a diagnosis of NAIT is detection of a human platelet antigen (HPA)‐specific antibody in maternal serum, together with identifying an incompatibility between the parents for the cognate HPA antigen, platelet genotyping is the gold standard method for HPA typing. Platelet genotyping is critical in screening at‐risk fetuses for the presence ofthe HPA corresponding to the maternal antibody. In addition, platelet genotyping may play a role in population screening to identify women at risk for sensitization, and thus, fetuses at risk for NAIT. The most commonly used methods of platelet genotyping are sequence‐specific primer‐polymerase chain reaction (PCR‐SSP), restriction fragment length polymorphism‐PCR (PCR‐RFLP), and TaqMan real‐time PCR. PCR‐SSP and PCR‐RFLP are relatively inexpensive and technically simple methods, but they are not easily automated and require expertise for reliable interpretation of results. Newer methods that allow for multiplexing, automation, and easily interpretable results, such as bead arrays, are currently in development and available for research purposes. Am. J. Hematol. 87:525–528, 2012.