Main erythrocyte antigens involved in the alloimmunization process

Erythrocyte alloimmunization occurs when an individual produces antibodies to antigens on the donor's red blood cell, which the immune system identifies as a foreign element to the organism. It represents one of the greatest risks faced by patients undergoing transfusion therapy, reducing the possibility of finding compatible red blood cells in future transfusions. The immune system of the human being has the ability to recognize what is proper to its genome from what is not proper, being able to stimulate an immune reaction against foreign substances. Upon contact with different antigens present in the donor red blood cell, the recipient of the blood may trigger an immune response by generating antibodies against nonself antigens due to sensitization, such as post-pregnancy or primary transfusion, which may trigger lysis of transfused red blood cells. Exposure to large numbers of nonself antigens may lead to the formation of alloantibodies causing intra- or extravascular haemolytic transfusion reaction. Polytransfused patients are more likely to develop alloantibodies, approximately 1% for each transfused unit. This percentage may be higher in sickle cell patients (36%), thalassemia patients (10%) and people with myelo and lymphoproliferative diseases (9%)

Leucoreduction of blood components. an effective way to increase blood safety?

Over the past 30 years, it has been demonstrated that removal of white blood cells from blood components is effective in preventing some adverse reactions such as febrile non-haemolytic transfusion reactions, immunisation against human leucocyte antigens and human platelet antigens, and transmission of cytomegalovirus. In this review we discuss indications for leucoreduction and classify them into three categories: evidence-based indications for which the clinical efficacy is proven, indications based on the analysis of observational clinical studies with very consistent results and indications for which the clinical efficacy is partial or unproven

Overview of the blood transfusion policy in preterms on the Neonatal Intensive Care Unit

Preterm infants on the Neonatal Intensive Care Unit receive a greater number of red cell transfusions than any other hospitalised group. Over the past twenty years research has focused on setting standards to determine when it is necessary to transfuse packed cells in this cohort, whilst exploring the use of red cell growth factors and other substrates judiciously in order to reduce and/or avoid red cell transfusions and limit donor exposure. One hundred and eighty-one blood transfusions were administered to 106 preterms less than 35 weeks gestation on the NICU during 2009 in Malta. The median (range) volume of blood used from each bag supplied by the Blood Transfusion Department was 25.8mls (10-50mls), the rest of which was discarded. Risk factors for transfusion included Extremely Low Birth Weight (less than 1kg) and a gestation of less than 30 weeks. The blood transfusion guidelines presently in use on the local NICU were reviewed and compared with more restrictive guidelines on other units and suggestions made to reduce transfusions in line with these guidelines. A reduction in transfusion aliquots provided for neonates to just 50mls from the customary 250mls in a dedicated single-donor programme will safeguard limited health resources and minimise donor exposure.peer-reviewe

Ferric carboxymaltose with or without erythropoietin for the prevention of red-cell transfusions in the perioperative period of osteoporotic hip fractures: a randomized contolled trial. The PAHFRAC-01 project

Background: Around one third to one half of patients with hip fractures require red-cell pack transfusion. The increasing incidence of hip fracture has also raised the need for this scarce resource. Additionally, red-cell pack transfusions are not without complications which may involve excessive morbidity and mortality. This makes it necessary to develop blood-saving strategies. Our objective was to assess safety, efficacy, and cost-effictveness of combined treatment of i.v. ferric carboxymaltose and erythropoietin (EPOFE arm) versus i.v. ferric carboxymaltose (FE arm) versus a placebo (PLACEBO arm) in reducing the percentage of patients who receive blood transfusions, as well as mortality in the perioperative period of hip fracture intervention. Methods/Design: Multicentric, phase III, randomized, controlled, double blinded, parallel groups clinical trial. Patients > 65 years admitted to hospital with a hip fracture will be eligible to participate. Patients will be treated with either a single dosage of i.v. ferric carboxymaltose of 1 g and subcutaneous erythropoietin (40.000 IU), or i.v. ferric carboxymaltose and subcutaneous placebo, or i.v. placebo and subcutaneous placebo. Follow-up will be performed until 60 days after discharge, assessing transfusion needs, morbidity, mortality, safety, costs, and health-related quality of life. Intention to treat, as well as per protocol, and incremental cost-effectiveness analysis will be performed. The number of recruited patients per arm is set at 102, a total of 306 patients. Discussion: We think that this trial will contribute to the knowledge about the safety and efficacy of ferric carboxymaltose with/without erythropoietin in preventing red-cell pack transfusions in patients with hip fracture. ClinicalTrials.gov identifier: NCT01154491

Replacing the Transfusion of 1-2 Units of Blood with Plasma Expanders that Increase Oxygen Delivery Capacity: Evidence from Experimental Studies.

At least a third of the blood supply in the world is used to transfuse 1-2 units of packed red blood cells for each intervention and most clinical trials of blood substitutes have been carried out at this level of oxygen carrying capacity (OCC) restoration. However, the increase of oxygenation achieved is marginal or none at all for molecular hemoglobin (Hb) products, due to their lingering vasoactivity. This has provided the impetus for the development of "oxygen therapeutics" using Hb-based molecules that have high oxygen affinity and target delivery of oxygen to anoxic areas. However it is still unclear how these oxygen carriers counteract or mitigate the functional effects of anemia due to obstruction, vasoconstriction and under-perfusion. Indeed, they are administered as a low dosage/low volume therapeutic Hb (subsequently further diluted in the circulatory pool) and hence induce extremely small OCC changes. Hyperviscous plasma expanders provide an alternative to oxygen therapeutics by increasing the oxygen delivery capacity (ODC); in anemia they induce supra-perfusion and increase tissue perfusion (flow) by as much as 50%. Polyethylene glycol conjugate albumin (PEG-Alb) accomplishes this by enhancing the shear thinning behavior of diluted blood, which increases microvascular endothelial shear stress, causes vasodilation and lowering peripheral vascular resistance thus facilitating cardiac function. Induction of supra-perfusion takes advantage of the fact that ODC is the product of OCC and blood flow and hence can be maintained by increasing either or both. Animal studies suggest that this approach may save a considerable fraction of the blood supply. It has an additional benefit of enhancing tissue clearance of toxic metabolites

Reduction of Oxidative Stress and Storage Lesions (RCSL) in Red Blood Cells: Analysis of Ascorbic Acid (AA), N-Acetylcysteine amide (AD4), and Serotonin (5-HT)

Oxidative stress is a common occurrence in red blood cell (RBC) storage in blood banks throughout the world. Typically RBC units stored under routine standard protocol (stored in SAGM-CPD additive solution) can only be kept up to forty-two days for transfusion usage before being discarded. I am studying the effects of Ascorbic Acid (AA), N-acetylcysteine amide (AD4), and Serotonin or 5-hydroxytryptamine (5- HT) as additives in blood bank storage to find out if these additives can reduce storageinduced oxidative stress on red blood cells (RBCs), as well as to understand how potential blood storage additives can affect the shelf life of blood and post-transfusion recovery in patients. I conducted a literature review by studying various journal articles that examined metabolism to proteomics and the synergy of the different additives. These various additives significantly alleviated a range of signs of oxidative stress on RBCs including but not limited to replenishing glutathione (GSH), decreasing percent hemolysis, inhibiting the phospholipid rearrangement, and encouraging ATP production. By reducing these symptoms of oxidative stress, RBCs are able to last longer without any significant changes biochemically, and decrease the chances of post-transfusion complications such as Graft vs Host Disease (GVHD). The new additive solution could potentially increase the patient’s post-transfusion recovery rates as well as increase the shelf life of RBC storage units past the standard forty-two days