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.

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.

Effect of fresh red blood cell transfusions on clinical outcomes in premature, very low-birth-weight infants: the ARIPI randomized trial.

Context: Even though red blood cells (RBCs) are lifesaving in neonatal intensive care, transfusing older RBCs may result in higher rates of organ dysfunction, nosocomial infection, and length of hospital stay.

Objective: To determine if RBCs stored for 7 days or less compared with usual standards decreased rates of major nosocomial infection and organ dysfunction in neonatal intensive care unit patients requiring at least 1 RBC transfusion.

Design, Setting, And Participants: Double-blind, randomized controlled trial in 377 premature infants with birth weights less than 1250 g admitted to 6 Canadian tertiary neonatal intensive care units between May 2006 and June 2011.

The role of comparative effectiveness research in transfusion medicine clinical trials: proceedings of a National Heart, Lung, and Blood Institute workshop.

Comparative effectiveness research (CER) is the study of existing treatments or ways to deliver health care to determine what intervention works best under specific circumstances. CER evaluates evidence from existing studies or generates new evidence, in different populations and under specific conditions in which the treatments are actually used. CER does not embrace one research design over another but compares treatments and variations in practice using methods that are most likely to yield widely generalizable results that are directly relevant to clinical practice.

Clinical review: Canadian National Advisory Committee on Blood and Blood Products--Massive transfusion consensus conference 2011: report of the panel.

In June 2011 the Canadian National Advisory Committee on Blood and Blood Products sponsored an international consensus conference on transfusion and trauma. A panel of 10 experts and two external advisors reviewed the current medical literature and information presented at the conference by invited international speakers and attendees. The Consensus Panel addressed six specific questions on the topic of blood transfusion in trauma.

Clinical trial opportunities in hemostasis and thrombosis: NHBLI State-of-the-Science symposium.

Clinical trials in hemostasis and thrombosis (HT) are needed to guide medical practice and future research. Providing public support for trials that could have the greatest impact on clinical care has been a major challenge. The National Heart, Lung and Blood Institute (NHLBI) convened a State-of-the-Science meeting in Bethesda on September 14th and 15th, 2009 to identify Phase II and III clinical trials in HT that could have critical impact on healthcare.

Proceedings of a consensus conference: Risk-Based Decision Making for Blood Safety.

Blood safety decision making has become increasingly complex, and a framework for risk-based decision making is, thus, needed. The purpose of this consensus conference was to bring together international experts in an effort to develop the foundations for such a framework. These proceedings are described with a view to making available to the transfusion medicine community the considerable amount of information and insight that was presented and that emerged through debate by the experts, panel members, and delegates.

The Age of Blood Evaluation (ABLE) randomized controlled trial: study design.

Red blood cells (RBCs) are transfused to treat anemia and to maintain oxygen delivery to vital organs during critical illness. Laboratory and observational studies have raised the possibility that prolonged RBC storage may adversely affect clinical outcomes. Compared with RBCs stored less than 1 week, there are no clinical data demonstrating that RBCs stored longer remain as effective at carrying or releasing oxygen, and observational studies have risen to possibility that prolonged RBC storage might result in harm to vulnerable patients requiring blood transfusions.

A multidisciplinary "think tank": the top 10 clinical trial opportunities in transfusion medicine from the National Heart, Lung, and Blood Institute-sponsored 2009 state-of-the-science symposium.

Background: In September 2009, the National Heart, Lung, and Blood Institute convened the State-of-the-Science Symposium in Transfusion Medicine to identify Phase II and/or III clinical trials that would provide important information to advance transfusion medicine.

Study Design And Methods: Seven multidisciplinary subcommittees developed proposals in the following areas: 1) platelet (PLT) product use, 2) neonatal and/or pediatric transfusion practice, 3) surgical transfusion practice, 4) intensive care unit and/or in trauma transfusion practice, 5) plasma and/or cryoprecipitate product use and therapeutic apheresis practice, 6) red blood cell (RBC) product use and/or blood conservation management, and 7) medical transfusion practice or blood donor studies. The committees consisted of transfusion medicine specialists, hematologists, cardiovascular surgeons, anesthesiologists, neonatologists, critical care physicians, and clinical trial methodologists.

Clinical trial opportunities in Transfusion Medicine: proceedings of a National Heart, Lung, and Blood Institute State-of-the-Science Symposium.

The use of blood products to support patients undergoing the large variety of medical and surgical interventions requiring such support has continued to escalate very significantly over time. Relevantly, significant practice variation in the use of blood products exists among practitioners and institutions, largely because of the lack of robust clinical trial data, in many instances, which are critical for providing practitioners with evidence-based guidelines for appropriate blood product utilization. Recognizing this gap, the National Heart, Lung, and Blood Institute recently established a State-of-the-Science Symposium to help define areas of clinical trial research that would enhance the opportunity for developing appropriate practice guidelines for both Transfusion Medicine and Hemostasis/Thrombosis.

Warm autoimmune hemolytic anemia: recent progress in understanding the immunobiology and the treatment.

Autoimmune hemolytic anemia (AIHA) is defined as a condition associated with the increased destruction of red blood cells (RBCs) associated with the presence of IgG anti-RBC autoantibodies. The etiology underlying the pathogenesis of such autoantibodies is still uncertain. In the present article, we will discuss the postulated mechanisms that produce a breakdown of immunologic tolerance leading to warm AIHA including the possible roles of RBC autoantigens and the complement system, the lack of effective presentation of autoantigens, functional abnormalities of B and T cells resulting in polyclonal lymphocyte activation and alteration of cytokine production, and the role of immunoregulatory T cells.

Blood still kills: six strategies to further reduce allogeneic blood transfusion-related mortality.

After reviewing the relative frequency of the causes of allogeneic blood transfusion-related mortality in the United States today, we present 6 possible strategies for further reducing such transfusion-related mortality. These are (1) avoidance of unnecessary transfusions through the use of evidence-based transfusion guidelines, to reduce potentially fatal (infectious as well as noninfectious) transfusion complications; (2) reduction in the risk of transfusion-related acute lung injury in recipients of platelet transfusions through the use of single-donor platelets collected from male donors, or female donors without a history of pregnancy or who have been shown not to have white blood cell (WBC) antibodies; (3) prevention of hemolytic transfusion reactions through the augmentation of patient identification procedures by the addition of information technologies, as well as through the prevention of additional red blood cell alloantibody formation in patients who are likely to need multiple transfusions in the future; (4) avoidance of pooled blood products (such as pooled whole blood-derived platelets) to reduce the risk of transmission of emerging transfusion-transmitted infections (TTIs) and the residual risk from known TTIs (especially transfusion-associated sepsis [TAS]); (5) WBC reduction of cellular blood components administered in cardiac surgery to prevent the poorly understood increased mortality seen in cardiac surgery patients in association with the receipt of non-WBC-reduced (compared with WBC-reduced) transfusion; and (6) pathogen reduction of platelet and plasma components to prevent the transfusion transmission of most emerging, potentially fatal TTIs and the residual risk of known TTIs (especially TAS).

Extending the horizon for cell-based immunotherapy by understanding the mechanisms of action of photopheresis.

Most of the current cell-based immunotherapy protocols concentrate on immune stimulatory effects against certain pathogenic insults, such as cancer. In this article, a potential cell-based immunotherapeutic strategy to induce immune tolerance by infusion of apoptotic leukocytes is presented in conjunction with a review of newly understood mechanisms of action of photopheresis and relevant information about allogeneic transfusion-related immunomodulation. The scientific rationale is discussed by examining our understanding of the role of apoptosis in self-antigen tolerance, the interaction between apoptotic bodies and antigen-presenting cells, and the subsequent induction of T regulatory cells and clonal deletion of effector T cells.

Research opportunities for pathogen reduction/inactivation of blood components: summary of an NHLBI workshop.

In July 2008, a workshop sponsored by the Division of Blood Diseases and Resources of the National Heart, Lung, and Blood Institute (NHLBI) was convened to identify potential research opportunities that could advance our understanding of both the biologic and the clinical impact of the various available pathogen reduction/inactivation (PR/PI) methods of blood components (platelets [PLTs], red blood cells, and plasma) intended for allogeneic transfusion. These discussions resulted in consensus that, even though several PR/PI technologies have already been licensed and are being used in Europe and elsewhere for PLTs and plasma, concerns about possible side effects, particularly component quality and pulmonary toxicity, have impeded regulatory approval in North America (United States and Canada). Such concerns thus threaten to stall further development of these technologies.

Severe hemolytic anemia post-renal transplantation produced by donor anti-D passenger lymphocytes: case report and literature review.

The passenger lymphocyte syndrome (PLS), often associated with immune-mediated hemolytic anemia after solid organ and hematopoietic stem cell transplantation, is the result of concomitant transplantation of donor lymphocytes along with the donor allograft. Antibodies directed against recipient red blood cells (RBCs) are frequently found in ABO-mismatched solid organ transplants; however, passenger lymphocyte-mediated hemolysis due to Rh-incompatible antibodies has only rarely been reported. In this report, we present a case of severe hemolytic anemia related to the PLS in an ABO-matched renal allograft recipient.

Transfusion-related mortality: the ongoing risks of allogeneic blood transfusion and the available strategies for their prevention.

As the risks of allogeneic blood transfusion (ABT)-transmitted viruses were reduced to exceedingly low levels in the US, transfusion-related acute lung injury (TRALI), hemolytic transfusion reactions (HTRs), and transfusion-associated sepsis (TAS) emerged as the leading causes of ABT-related deaths. Since 2004, preventive measures for TRALI and TAS have been implemented, but their implementation remains incomplete. Infectious causes of ABT-related deaths currently account for less than 15% of all transfusion-related mortality, but the possibility remains that a new transfusion-transmitted agent causing a fatal infectious disease may emerge in the future.

New strategies for the optimal use of platelet transfusions.

Patients with severe thrombocytopenia are presumed to be at increased risk for bleeding, and consequently it has been standard practice for the past four decades to give allogeneic platelet transfusions to severely thrombocytopenic patients as supportive care. Platelet transfusions may be given either prophylactically to reduce the risk of bleeding, in the absence of clinical hemorrhage (prophylactic transfusions), or to control active bleeding when present (therapeutic transfusions). While no one would argue with the need for platelet transfusions in the face of severe bleeding, important questions remain about what constitutes clinically significant bleeding and whether a strategy of prophylactic platelet transfusions is effective in reducing the risk of bleeding in clinically stable patients.

A comparison of aprotinin and lysine analogues in high-risk cardiac surgery.

Background: Antifibrinolytic agents are commonly used during cardiac surgery to minimize bleeding and to reduce exposure to blood products. We sought to determine whether aprotinin was superior to either tranexamic acid or aminocaproic acid in decreasing massive postoperative bleeding and other clinically important consequences.

Methods: In this multicenter, blinded trial, we randomly assigned 2331 high-risk cardiac surgical patients to one of three groups: 781 received aprotinin, 770 received tranexamic acid, and 780 received aminocaproic acid.

Why implement universal leukoreduction?

The improvement of transfusion medicine technology is an ongoing process primarily directed at increasing the safety of allogeneic blood component transfusions for recipients. Over the years, relatively little attention had been paid to the leukocytes present in the various blood components. The availability of leukocyte removal (leukoreduction) techniques for blood components is associated with a considerable improvement in various clinical outcomes.

Transfusion-related immunomodulation due to peripheral blood dendritic cells expressing the CD200 tolerance signaling molecule and alloantigen.

Background: The transfusion of allogeneic blood products containing white cells (WBCs) has been reported to reduce resistance to infection, stimulate the growth of some types of tumors in animal models, and prevent abortion of allogeneic embryos in the CBAxDBA/2 murine model.

Study Design And Methods: In this study, the issue explored was whether allogeneic BALB/c whole blood given to C57Bl/6 mice by tail vein after injection of syngeneic FSL-10 fibrosarcoma cells increased the number of lung nodules enumerated on Day 21. The effect on the tumor growth-promoting effect produced by allogeneic BALB/c whole blood was then examined by exposure of the allogeneic BALB/c blood to various monoclonal antibodies (MoAbs).

CD200-dependent and nonCD200-dependent pathways of NK cell suppression by human IVIG.

Problem: Intravenous immunoglobulin (IVIG) has been used to suppress autoimmune and inflammatory disorders by a variety of mechanisms. Recently, the CD200 tolerance-promoting signal has been found to play a role in IVIG suppression of blood natural killer (NK) cells. Further, different types of IVIG have been reported to differ in this activity, and that has been related to efficacy (and inefficacy) of treatment of women with pregnancy failure.

Proceedings of a Consensus Conference: pathogen inactivation-making decisions about new technologies.

Significant progress has been made in reducing the risk of pathogen transmission to transfusion recipients. Nonetheless, there remains a continuing risk of transmission of viruses, bacteria, protozoa, and prions to recipients. These include many of the viruses for which specific screening tests exist as well as pathogens for which testing is currently not being done, including various species of bacteria, babesiosis, variant Creutzfeld-Jacob disease, hepatitis A virus, human herpes virus 8, chikungunya virus, Chagas disease, and malaria.