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Canada's per capita use of intravenous immune globulin (IVIG) grew by approximately 115% between 1998 and 2006, making Canada one of the world's highest per capita users of IVIG. It is believed that most of this growth is attributable to off-label usage. To help ensure IVIG use is in keeping with an evidence-based approach to the practice of medicine, the National Advisory Committee on Blood and Blood Products (NAC) and Canadian Blood Services convened a panel of national experts to develop an evidence-based practice guideline on the use of IVIG for neurologic conditions. The mandate of the expert panel was to review evidence regarding use of IVIG for 22 neurologic conditions and formulate recommendations on IVIG use for each. A panel of 6 clinical experts, one expert in practice guideline development and 4 representatives from the NAC met to review the evidence and reach consensus on the recommendations for the use of IVIG. The primary sources used by the panel were 2 recent evidence-based reviews. Recommendations were based on interpretation of the available evidence and, where evidence was lacking, consensus of expert clinical opinion. A draft of the practice guideline was circulated to neurologists in Canada for feedback. The results of this process were reviewed by the expert panel, and modifications to the draft guideline were made where appropriate. This practice guideline will provide the NAC with a basis for making recommendations to provincial and territorial health ministries regarding IVIG use management. Recommendations for use of IVIG were made for 14 conditions, including acute disseminated encephalomyelitis, chronic inflammatory demyelinating polyneuropathy, dermatomyositis, diabetic neuropathy, Guillain-Barré syndrome, Lambert-Eaton myasthenic syndrome, multifocal motor neuropathy, multiple sclerosis, myasthenia gravis, opsoclonus-myoclonus, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, polymyositis, Rasmussen's encephalitis, and stiff person syndrome; IVIG was not recommended for 8 conditions including adrenoleukodystrophy, amyotropic lateral sclerosis, autism, critical illness polyneuropathy, inclusion body, myositis, intractable childhood epilepsy, paraproteinemic neuropathy (IgM variant), and POEMS syndrome. Development and dissemination of evidence-based clinical practice guidelines may help to facilitate appropriate use of IVIG.

Transfusion-related acute lung injury is a relatively uncommon transfusion-associated adverse effect occurring during or soon after an allogeneic blood transfusion. Transfusion-related acute lung injury is a complex syndrome that has many manifestations and has only recently been identified to be an important cause of transfusion-associated morbidity and mortality. But despite its increasing recognition, much about the pathogenesis, treatment, and prevention is poorly understood and often controversial. The purpose of this consensus conference was to bring together international experts in an effort to try to standardize a case definition, which could be used to enhance future understanding of transfusion-related acute lung injury including its epidemiology, pathogenesis, management, prevention, and research. These proceedings are being provided with a view to making available to the transfusion medicine community the considerable amount of important information presented at this consensus conference by the invited international panel of experts.

Routine platelet transfusions for patients with acute leukemia were introduced in the early 1960s, and since then platelet use has increased steadily. Despite widespread use, good clinical evidence supporting prophylactic platelet transfusions is limited, and there are very few studies that have examined the dose for prophylactic platelet transfusions. Review of the platelet dose used in both early studies of routine platelet transfusions and more recent clinical trials of platelet transfusions shows wide variation in dosing, which is also reflected in clinical practice. As such, only limited recommendations for platelet dose have been forthcoming from consensus conferences or guidelines. The results from 3 recent clinical trials and a mathematical model examining the dose for prophylactic platelet transfusions suggest that lower dose transfusions may decrease the total number of platelets transfused; however, no definitive conclusions about the optimal platelet dose can be reached as these trials were not designed to evaluate bleeding outcomes or total platelet utilization. Future large clinical trials of platelet dose, which examine these critical outcomes, are required. Only with these results can the optimal platelet dose be determined.

Autoimmune thrombocytopenic purpura (AITP) is a bleeding disorder in which autoantibodies are directed against an individual's own platelets, leading to enhanced clearance through Fc receptor (R)-mediated phagocytosis by macrophages residing in the reticuloendothelial system (RES), particularly in the spleen. The production of IgG autoantibodies is critically dependent on cellular immune mechanisms particularly relating to T cells. We review the recent literature of the cell-mediated immunology of AITP focusing on platelet phenotype, genetics, T-cell reactivities, and cytokine profiles in patients with AITP. Understanding the interaction between these cell-mediated mechanisms is vital for developing antigen specific immunotherapies to treat this autoimmune disease.

This guideline for the use of immunoglobulin (IG) for sensitized patients undergoing solid organ transplantation (SOT) is an initiative of the Canadian Blood Services and the National Advisory Committee on Blood and Blood Products of Canada to (1) provide guidance for Canadian practitioners involved in the care of patients undergoing SOT and transfusion medicine specialists on the use of IG and (2) standardize care, limit adverse events, and optimize patient care. A systematic expert and bibliography literature search up to July 2008 was conducted, with 791 literature citations and 45 reports reviewed. To validate the recommendations, the guideline was sent to physicians involved in SOT in Canada and a patient representative. The recommendations identify (1) sensitized patients undergoing SOT that would have a better survival and decreased morbidity by receiving IG preoperatively, postoperatively, and for the treatment of organ rejection; (2) patients who may not have any benefit from receiving IG; and (3) potential adversities to IG.

UTOIMMUNE HEMOLYTIC anemia (AIHA) is an acquired immunoIogic disease in which the patient's red blood cells (RBCs) are selectively attacked and destroyed (hemolyzed) by autoantibodies produced by the patient's own immune system. These patients generally display the common symptoms of anemia: weakness, pallor, fatigue, and jaundice. Less obvious is the frequent occurrence of mild splenomegaly. There are 2 major types of AIHA: cold agglutinin disease (CAD) and warm autoimmune hemolytic anemia (WAIHA), which are differentiated by the optimal temperature of reactivity of the autoantibody. A third type of AIHA is the relatively uncommon, but quite distinct, paroxysmal cold hemoglobinuria (PCH). The pathophysiologic mechanisms differ for the different types of AIHA, depending on autoantibody immunoglobulin class and subclass and the ability of the antibody to activate complement. The degree of RBC hemolysis depends, in part at least, on the autoantibody concentration in the patient's blood and on the abifity of the antibody to activate complement. In CAD, the autoantibodies are immunoglobulin M (IgM) immunoglobulins; in WAIHA, the autoantibodies are IgG immunoglobulins. RBCs coated with IgG autoantibody undergo extravascular destruction, primarily in the spleen, whereas RBCs coated with complement (mediated by IgM and some IgG autoantibodies) can be destroyed either intravascularly or extravascularly. Although it may occur in both the warm and cold types of AIHA, intravascular hemolysis is classically more associated with CAD (and with PCH) ,and leads to increased plasma hemoglobin and hemoglobinuria, resulting in red, brown, or tea-colored plasma and urine. Extravascular destruction of the RBC (classic in WAIHA, but also common in CAD) results in increased bilirubin in the plasma and urine urobilin, resulting in jaundice and dark yellow urine. AIHA is further classified into (1) primary or idiopathic, in which no associated disease is identified, and (2) secondary, associated with collagenvascular disorders such as systemic lupus erythematosus (SLE), lymphomas and leukemias, rheumatoid arthritis, ulcerative colitis, lupoid hepatitis, etc. Whereas both secondary WAIHA and CAD have been associated with SLE, lymphomas, and leukemias, secondary CAD is also known to result from infectious mononucleosis and Mycoplasma pneumoniae infections. PCH, which has historically been associated with syphilis, has more recently been more commonly associated with rubella and other virus infections and may be idiopathic in some cases. The main current treatments for WAIHA are corticosteroids, splenectomy, and immunosuppressive drugs, with a wide variety of therapies employed with varying success in cases resistant to the three approaches. CAD is treated by keeping the patient warm, blood transfusions, and plasmapheresis.

T RANSFUSION medicine has become a multidisciplinary field with many recent developments that continue to challenge the classical immune-technologies currently in use. Laserbased flow-cytometric analysis is a relatively recent technology that has had widespread application in medical and biologic research, and has been used with increasing regularity in transfusion medicine. The flow cytometer has had an impact in the field of transfusion medicine because of its ability to analyze individual populations of cells and cell epitopes by sensitive, reproducible, and objective methods. This is because of the use of highly specific fluorochrome-labeled monoclonal antibodies and the ability to evaluate large numbers of cells in a short time. Another advantage of flowcytometric analysis stems from the ability to retain results as permanently stored computer files that, at the analytical level, can be readily accessed to re-examine and re-analyze experiments performed in the past. There is a considerable body of literature on the application of flow cytometry to a wide diversity of medical diagnosis and research and these are listed, in part, in Table 1. The technology has been applied to examine all of the cell populations found in blood and, over the past decade, the technology has moved from research laboratories to clinical laboratories, primarily because of advances in the specificity and reproducibility of the probes (monoclonal antibodies), the ease of instrumentation, and the enhancement of computer power. This review focuses on the use of the flow cytometer in transfusion medicine, with attention to investigations of red blood cells (RBC), platelets, and white blood cells (WBC), as indicated in Table 2. Earlier work in this area was reviewed in 1988 by Nance 1 and emphasis will be on developments and applications over the past 6 years.