αI-spectrin represents evolutionary optimization of spectrin for red blood cell deformability

Spectrin tetramers of the membranes of enucleated mammalian erythrocytes play a critical role in red blood cell survival in circulation. One of the spectrins, αI, emerged in mammals with enucleated red cells following duplication of the ancestral α-spectrin gene common to all animals. The neofunctionalized αIspectrin has moderate affinity for βI-spectrin, while αII-spectrin, expressed in non-erythroid cells, retains ancestral characteristics and has a 10-fold higher affinity for βI-spectrin. It has been hypothesized that this adaptation allows for rapid make-and-break of tetramers to accommodate membrane deformation. We have tested this hypothesis by generating mice with high-affinity spectrin tetramers formed by exchanging the site of tetramer formation in αI-spectrin (segments R0 and R1) for that of αII-spectrin. Erythrocytes with αIIβI presented normal hematologic parameters yet showed increased thermostability and their membranes were significantly less deformable: under low shear forces they displayed tumbling behavior, rather than tank-treading. The membrane skeleton is more stable with αIIβI and shows significantly less remodeling under deformation than red cell membranes of wild-type mice. These data demonstrate that spectrin tetramers undergo remodeling in intact erythrocytes and that this is required for the normal deformability of the erythrocyte membrane. We conclude that αI-spectrin represents evolutionary optimization of tetramer formation: neither higher affinity tetramers (as shown here) nor lower affinity (as seen in hemolytic disease), can support the membrane properties required for effective tissue oxygenation in circulation

Dose of Prophylactic Platelet Transfusions and Prevention of Hemorrhage

We conducted a trial of prophylactic platelet transfusions to evaluate the effect of platelet dose on bleeding in patients with hypoproliferative thrombocytopenia

Handbook of transfusion medicine /

Handbook of Transfusion Medicine is unique in that it provides a comprehensive and practical description of all blood products and blood cell types currently used in transfusions, their appropriate applications, pathophysiology of conditions managed by transfusion, and pathophysiology of adverse reactions. Each chapter follows a standard format including numerous tables and algorithms, with summary elements highlighted throughout by a second-color for quick reference. Sections Include: * Blood collection and testing * Blood component description * Preparation and usage * Red blood cell antigens and antibodies * Specialized component processing * Specialized transfusion situations * Transfusion-transmitted diseases * Transfusion reactions * Infectious complications of transfusion * Therapeutic apheresis and quality * Acute bleeding and massive transfusion * Transfusion of the patient with a coagulopathy * Transfusion of obstetrics, pediatric, immunocompromised, and platelet refractory patients * Up-to-date references to all aspects of transfusion medicine.Handbook of Transfusion Medicine is unique in that it provides a comprehensive and practical description of all blood products and blood cell types currently used in transfusions, their appropriate applications, pathophysiology of conditions managed by transfusion, and pathophysiology of adverse reactions. Each chapter follows a standard format including numerous tables and algorithms, with summary elements highlighted throughout by a second-color for quick reference. Sections Include: * Blood collection and testing * Blood component description * Preparation and usage * Red blood cell antigens and antibodies * Specialized component processing * Specialized transfusion situations * Transfusion-transmitted diseases * Transfusion reactions * Infectious complications of transfusion * Therapeutic apheresis and quality * Acute bleeding and massive transfusion * Transfusion of the patient with a coagulopathy * Transfusion of obstetrics, pediatric, immunocompromised, and platelet refractory patients * Up-to-date references to all aspects of transfusion medicine.Blood Collection, Testing, and Processing -- Introduction to Blood Donors and Donation. -- Infectious Disease Testing. -- Component Preparation and Storage. -- Blood Components -- Packed Red Blood Cells and Related Products. -- Fresh Frozen Plasma and Related Products. -- Cryoprecipitate and Related Products. -- Platelets and Related Products. -- Granulocytes. -- Coagulation Factor Concentrates. -- Albumin, Gamma Globulin and Related Derivatives. -- Red Blood Cell Antigens and Antibodies -- Red Blood Cell Antigens and Human Blood Groups. -- Pre-Transfusion Compatibility Testing. -- Special Investigations in the Work-Up of Unexpected Antibodies and Blood Group Incompatibilities. -- Specialized Component Processing or Testing -- Leukoreduced Products. -- CMV and Other Virus-Safe Products. -- Irradiated Components. -- Washed and Volume-Reduced Components. -- Hematopoietic Stem Cells and Related Cellular Products -- Bone-Marrow-Derived Hematopoietic Progenitor Cells. -- Peripheral-Blood-Derived Hematopoietic Progenitor Cells. -- Umbilical Cord Blood Stem Cells. -- Mononuclear Cell Preparations. -- Specialized Transfusion Situations -- Approach to Acute Bleeding and Massive Transfusion. -- Evaluation of the Bleeding Patient. -- Approach to the Platelet Refractory Patient. -- Approach to Transfusion in Obstetrics: Maternal and Fetal Considerations. -- Transfusion Management of Infants and Children. -- Approach to the Immunocompromised Patient. -- Transfusion Reactions -- Acute and Delayed Hemolytic Transfusion Reactions. -- Febrile nonhemolytic Transfusion Reactions. -- Allergic Transfusion Reactions. -- Other Non-infectious Complications of Transfusion. -- Infectious Complications of Transfusion -- Hepatitis. -- CMV and Other Herpesviruses. -- HIV and HTLV. -- Other Transfusion-Transmitted Infections. -- Bacterial Contamination of Blood Products. -- Therapeutic Apheresis -- Overview and Practical Aspects of Therapeutic Apheresis. -- Therapeutic Plasma Exchange: Rationales and Indications. -- Therapeutic Cytapheresis: Red Blood Cell Exchange, Leukapheresis, and Thrombocytopheresis (Plateletpheresis). -- Consent, Quality and Related Issues -- Informed Consent for Transfusion. -- Home Transfusion. -- Lookback and Recipient Notification, Product Recalls and Withdrawls. -- Process Improvement: One Essential of a Quality System.Includes bibliographical references and index.Print version record.Elsevie

Editorial Ex Vivo Generated Red Cells as Transfusion Products

License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. This issue of the Stem Cell International journal contains papers from many of the leading scientists in the emerging field: ex vivo expansion of hematopoietic progenitor cells into erythrocytes for transfusion. Blood transfusion, the first form of successful cell therapy and, at least to some, “transplantation”, was inspired by the discovery of the circulation by Richard Harvey in the 1600s [1] and begun in earnest later in that century. The development of this clinical practice into the safe and routine therapy we all know today has been both an exciting scientific adventure and the foundation for a number of other scientific disciplines. More specifically, the immunology of transfusion and transplantation began with the discover