The Story of Blood for Shock Resuscitation: How the Pendulum Swings.

Whole blood transfusion (WBT) began in 1667 as a treatment for mental illness, with predictably poor results. Its therapeutic utility and widespread use were initially limited by deficiencies in transfusion science and antisepsis. James Blundell, a British obstetrician, was recognized for the first allotransfusion in 1825. However, WBT did not become safe and therapeutic until the early 20th century, with the advent of reliable equipment, sterilization, and blood typing. The discovery of citrate preservation in World War I allowed a separation of donor from recipient and introduced the practice of blood banking. During World War II, Elliott and Strumia were the first to separate whole blood into blood component therapy (BCT), producing dried plasma as a resuscitative product for "traumatic shock." During the 1970s, infectious disease, blood fractionation, and financial opportunities further drove the change from WBT to BCT, with few supporting data. Following a period of high-volume crystalloid and BCT resuscitation well into the early 2000s, measures to avoid the resulting iatrogenic resuscitation injury were developed under the concept of damage control resuscitation. Modern transfusion strategies for hemorrhagic shock target balanced BCT to reapproximate whole blood. Contemporary research has expanded the role of WBT to therapy for the acute coagulopathy of trauma and the damaged endothelium. Many US trauma centers are now using WBT as a front-line treatment in tandem with BCT for patients suffering hemorrhagic shock. Looking ahead, it is likely that WBT will once again be the resuscitative fluid of choice for patients in hemorrhagic shock.

Historical Perspectives, Current Status, and Ethical Issues in Granulocyte Transfusion.

The goal of this commentary is to provide a historical aspect of granulocyte transfusion, present practices in granulocyte transfusion, accentuate the complexity of the issue, and foster contemplation of ethical issues assimilated with this practice. Clinical aspects of granulocyte transfusion in the light of ethical issues are also discussed.

Plasma Transfusion: History, Current Realities, and Novel Improvements.

Traumatic hemorrhage is the leading cause of preventable death after trauma. Early transfusion of plasma and balanced transfusion have been shown to optimize survival, mitigate the acute coagulopathy of trauma, and restore the endothelial glycocalyx. There are a myriad of plasma formulations available worldwide, including fresh frozen plasma, thawed plasma, liquid plasma, plasma frozen within 24 h, and lyophilized plasma (LP). Significant equipoise exists in the literature regarding the optimal plasma formulation. LP is a freeze-dried formulation that was originally developed in the 1930s and used by the American and British military in World War II. It was subsequently discontinued due to risk of disease transmission from pooled donors. Recently, there has been a significant amount of research focusing on optimizing reconstitution of LP. Findings show that sterile water buffered with ascorbic acid results in decreased blood loss with suppression of systemic inflammation. We are now beginning to realize the creation of a plasma-derived formulation that rapidly produces the associated benefits without logistical or safety constraints. This review will highlight the history of plasma, detail the various types of plasma formulations currently available, their pathophysiological effects, impacts of storage on coagulation factors in vitro and in vivo, novel concepts, and future directions.

Transfusion guidelines: when to transfuse.

Transfusion of blood and blood components has been a routine practice for more than half a century. The rationale supporting this practice is that replacement of blood loss should be beneficial for the patient. This assumption has constituted the underpinning of transfusion medicine for many decades. Only over the past 20 years, we have seen a more concerted effort to answer very basic questions regarding the value of transfusion therapy. An assessment of the value of transfusion based on well-designed and appropriately powered randomized, controlled trials is the first step in optimizing transfusion practices. Systematic reviews provide the second step by building the knowledge base necessary to assess the impact of transfusion practice on patient outcomes. The third step is the development of clinical practice guidelines, and this occurs when systematic reviews are interpreted by individuals with expertise in transfusion medicine. Such guidelines are typically supported by professional organizations and/or health authorities. Implementation of clinical practice guidelines can be challenging, especially in an area as heterogeneous as transfusion medicine. However, clinical practice guidelines are necessary for the practice of evidence-based medicine, which optimizes patient care and improves patient outcomes. This review focuses on clinical practice guidelines for transfusion of three blood components: RBCs, platelets and plasma. In addition, we provide the approach used to implement clinical practice guidelines at our own institution.

Haemophilia, human immunodeficiency virus and human immunodeficiency virus pathogenesis.

In July 1982, the occurrence of three cases of acquired immunodeficiency syndrome (AIDS) in men with haemophilia was an immediate signal to Oscar Ratnoff that AIDS was transmissible through blood products. Work that he led provided important and clear indication that the AIDS agent was transmissible through pooled plasma products and had rapidly infected many men who had haemophilia. Before the blood supply was protected, the risk for infection in haemophilia was related directly to the intensity of therapy with pooled anti-haemophilic factor concentrates. Studies performed among the small proportion of haemophiliacs who remained uninfected despite heavy exposure to these plasma products revealed that the rare protective genotype - homozygosity for the 32 base pair deletion in the CCR5 gene was heavily concentrated in this population. Among those who did not have this protective genotype, a state of diminished immune activation distinguished these high risk uninfected haemophiliacs from haemophiliacs who later acquired human immunodeficiency virus (HIV) infection and from healthy uninfected controls. Immune activation state may not only predict risk for HIV acquisition but also appears to be an important predictor and likely determinant of HIV disease progression. The potential drivers of immune activation in chronic HIV infection include HIV itself, other co-infecting pathogens, homeostatic responses to cytopenia as well as the recently recognised phenomenon of translocation of microbial products across a damaged gut mucosal surface. This latter process is particularly compelling as clinical studies have shown a good relationship between indices of microbial translocation and markers of both immune activation and T cell homeostasis in chronic HIV infection. More recently, we have also found evidence that these microbial products also may drive a heightened tendency to thrombus formation in HIV infection via induction of monocyte tissue factor expression. Thus systemic exposure to microbial elements that are translocated through a gut mucosa damaged in the first few weeks of HIV infection may contribute to the pathogenesis of both immune deficiency and the heightened risk for vascular events that have been noted in persons with HIV infection.

Transfusion-related lung injury.

This paper describes the history and pathogenesis of TRALI and illustrates this with personal experience of the condition over 15 years at a single hospital. It discusses the contribution of transfusion to ALI seen in critically ill patients, and the effect of preventative measures taken in the UK.

David B. Pall, PhD (1914-2004).

In this edition of the Pioneers and Pathfinders Series, the contributions of David B. Pall, PhD, to transfusion medicine are discussed. With the aid of Dr Pall's unpublished personal history and assistance from family members and the company he founded, we are able to provide perspective to several remarkable scientific advances. For those of us in transfusion medicine, the discovery of the world's first leukoreduction filter prevails as his most significant invention. However, to the rest of the world, Dr Pall pioneered filtration with applications in aerospace, microelectronics, general industry, and most recently, contamination control. The almost 60-year-old Pall Corporation continues to preserve his legacy.

History of plasma-product safety.

The evolution of transfusion or infusion therapies for diseases requiring specific protein replacements (e.g., hemophilia A and B and severe combined immunodeficiency syndrome) was dramatic over the second half of the 20th century. Unfortunately, it was accompanied by extreme manifestations of transfusion-transmitted diseases, such as human immunodeficiency virus (HIV), hepatitis B, and hepatitis C. The milestones of both the replacement therapies and the associated diseases are discussed in this presentation, which focuses on the technologic advances that resulted in even more "pure" replacement therapies for plasma-protein diseases. From donor screening to the development of viral attenuation techniques, every facet of production for these products was impacted by the exigent push for viral safety created by HIV and hepatitis. Almost invariably, this negatively affects total product yield. At the beginning of the 21st century, success in making plasma products safe from recognized and potential pathogens has dramatically increased societal pressures to produce a zero-risk, plasma-derived protein therapy. However, past improvements and low theoretic risks for future pathogen contamination have increased product cost. This is associated with a possible decrease in the overall supply of these plasma proteins because of the reduced numbers of acceptable donors and the loss of protein from expanded attenuation technology. These impacts and the role of dynamic societal and scientific pressures on these decision processes are discussed.

Neocyte transfusion: a current perspective.

The most important studies published to date concerning the methods of preparation and the clinical utility of young red blood cells are reviewed 20 years after the first discoveries were made in this field. The results of each of the seven methods utilized (cells separators, cell washers, manual methods, etc.) are analyzed and the author's opinion is given concerning the results of in vitro and in vivo application. With few exceptions, the reviewed studies were done using small numbers of individuals. The majority of the studies confirm that it is possible to obtain YRBC enriched units. They also agree that YRBC have a higher survival rate in vivo than do normal RBC. In contrast, many of the wider-based studies did not show positive results when YRBC were used in patients or the results were too weak to justify the large amount of time and money these methods demand. Based on the review of all of the investigations published to date, there is little evidence to sustain the assumption of the clinical utility of YRBC used for multitransfused patients.