Learning Objectives:To identify some of the common adverse transfusion reactions and cite initial clinical management.To enumerate investigation techniques from some of the developed nations in the world.AbstractBlood Transfusion is a clinical management that primarily aims to aid in the diagnosis of the patient primarily to correct anemia. But to due unexpected circumstances, this procedure sometimes causes adverse reactions which leads to injury and death. Proper education and prompt recognition and investigation of these events must be establish in order to prevent further damage.IntroductionBlood Transfusion has been considered one of the many factors of the modern healthcare. It is only necessary to give importance on the appropriate handling and processing of blood and blood products. This is to guarantee its safety and efficacy prior to blood transfusion procedure. National health standards wants to ensure that benefit due to patient is given in the course of their clinical management. Different countries have different ways of dealing with general events such as weather conditions, quality of roads and highways, dependability of power and water supply as well as the methods of transportation. These significantly influence the access to healthcare and treatment which encompasses a safe and sufficient blood supply. Safety of blood and blood product has been a delevoping area of focus for many countries in the world over the recent years. The World Health Organization, with International Society of Blood Transfusion, advocates efforts for improving access to safe blood and blood product transfusion across the world. The safety of blood starts with blood donor recruitment and consists of the following:Emphasis on pre-donation information;Blood component collection, preparation, and testing;Post-donation information collection;Labeling of the blood products for distribution;Handling of blood products in the hospital inventory;Blood transfusion into the patient by hospital staff; andCulminating with hemovigilance and clinical quality improvement to ensure patient safety and to reduce the morbidity and mortality associated with blood transfusion.A number of ways have been identified in reducing the risks of blood transfusions and enhance the safety of blood and blood products. There are interventions during the process from prior the blood donation collection itself through post-procedure follow-up of blood product recipients. Improvements in the collection, storage, management, distribution, utilization and monitoring of transfusions have been observed. Despite the presence of these standardized programs for a safe blood and blood transfusion, unforeseen events still take place.An adverse reaction is an unwanted response in a patient which is linked with the administration of blood or blood component. Nowadays, one of the greatest complications which results to patients’ morbidity and mortality is related to the non-infectious effects of transfusions. It cannot be anticipated which patients will have such response, so it is only necessary for the laboratory personnel and other healthcare providers involved to have an insight of the different types of transfusion reactions and the steps to be executed to prevent further injury.ACUTE NON-INFECTIOUS BLOOD TRANSFUSION ADVERSE REACTIONSFebrile Non-Hemolytic Transfusion ReactionFebrile Non-Hemolytic Transfusion Reaction is characterized by an increase of 1 degree Centigrade that is usually observed within 2 hours of transfusion. This may be represented with the presence of fever accompanied by chills, cold, rigor and discomfort. It is said to be associated with leukocytes, either leukocyte derived cytokines or recipient WBC antibodies against leukocytes transfused. Antipyretic medications are prescribed to bring the normal body temperature back. Before the diagnosis of this adverse reaction, it is better to eliminate other causes of fever.Allergic reactionsThe symptoms of this adverse reaction may either take effect within seconds or minutes of the start of the transfusion procedure or may take some hours to occur.UrticariaUrticaria is the mildest form of an allergic reaction that occur abruptly. It usually causes itching that lasts for several hours or days before it disappears. A more serious case of this may be associated with angioedema. Once the symptoms diminished, the transfusion may be continued. Severe reactions may be managed with methylprednisolone (125 mg intravenously) or prednisone (50 mg orally).AnaphylaxisAnaphylaxis is a more serious type of allergic reaction that can be life-threatening. Severe hypotension, shock, and loss of consciousness may be observed. It is usually noted in IgA deficient recipients where it is originated from the antibodies against donor IgA. If the patient is unconscious or in shock, administer adrenaline intravenously coupled with cardiac monitoring.NON-IMMUNE HEMOLYTIC REACTIONSTransfusion associated circulatory overloadMajor morbidity and mortality is associated with transfusion-associated circulatory overload. Elderly patients, infants, patients with renal failure, having hypoalbuminaemia, anaemia, congestive heart failure or fluid overload or history of plasma transfusion are at greater risk. Clinical sign and symptoms may be dyspnoea, orthopnoea, cyanosis, tachycardia, jugular venous distension, and pedal oedema. Management is an optimization of the primary cause and mechanical ventilation, fluid restriction, diuretics.Citrate toxicityIn the event where large volumes of blood components with citrate anticoagulant are transfused at an accelerated rate, increased plasma citrate chelates calcium ions resulting in hypocalcemia. Hypocalcemia is caused by citrate overload which can be corrected by slowing down the transfusion process. Calcium replacement is indicated in massively transfused patients.HypothermiaThis may occur by tranfusion of large volume of cold blood components. It can lead to cardiac arrythmia and can also affect platelet function. The use of blood warmers is recommended to prevent this type of adverse reaction. It should also be noted that blood should never be warmed using equipment that are not made to cater this purpose. Blood cells and proteins may result in serious adverse reaction due to thermal damage if not prevented.DELAYED NON-IMMUNE MEDIATED REACTIONSIron overloadPatients with thalassemia, sickle cell disease or any other chronic anemia are at a much risk for iron overload. One unit of red blood cells has approximately 250 mg of iron. The moment when RBCs are hemolysed, the majority of the iron released cannot be excreted and therefore stored in the body as hemosiderin and ferritin. Transferrin gets saturated after the administration of 10 to 15 units of RBCs to a non-bleeding patient. Iron is increased in the the reticuloendothelial system, liver, heart, spleen, and endocrine organs causing tissue damage leading to heart failure, liver failure, diabetes and hypothyroidism.DELAYED IMMUNE MEDIATED REACTIONSTransfusion‑Associated Graft Versus Host DiseaseTransfusion-associated graft versus host disease (TA-GVHD) is a clinical syndrome manifested by fever, maculopapular rash which eventually progress to haemorrhagic bullae, enterocolitis with watery diarrhea, elevated liver function tests, pancytopenia. Findings of characteristic histological appearances on biopsy usually starts 8 to 10 days after transfusion. In TA-GVHD, viable transfused T-lymphocytes mount an immunologic attack against the immunocompromised recipient incapable of rejecting the immunocompetent cells. TA-GVHD can also happen after the transfusion from a blood related donor who is homozygous for an HLA haplotype to a heterozygous patient. HLA typing and other molecular studies can detect chimerism and thus help in the diagnosis. Therefore, it is important to empahsize that through the irradiation of cellular blood components (RBCs, platelets, and granulocytes) prior to transfusion aid in the prevention of the said adverse reaction.Having discussed some of the adverse transfusion reactions, it is therefore critical to monitor patients throughout a transfusion process. The recognition of these reactions may be improved by asking patients to report any signs and symptoms if these develop during the transfusion. It is necessary to know what to do during these unwanted events. Nations throughout the world have different ways on how to deal with these circumstances and this paper aims to discuss investigations of transfusion reactions from some of the developed countries. The main objective of these investigations is to identify patients with life-threatening adverse reactions and how to de-escalate and eventually avoid these to happen.The first step in dealing with any adverse reaction is to discontinue the transfusion. Venous access must be maintained using normal saline while the patient is being assessed which includes the patient’s airway, breathing and circulation. The patient’s details which can be found on their wrist band should be verified to ensure that they correspond with those on the blood component compatibility label. Finally, the blood unit that is being transfused must be assessed for its color and for the presence of unusual clumps, particulate matter or discoloration which may be brought by bacterial contamination.Department of Health and Community Services Provincial Blood Coordinating ProgramCanadaAfter an initial assessment, personnel from Department of Health and Community Services Provincial Blood Coordinating Program, Canada proceeds to the post-transfusion investigations. Collection of specimen after the transfusion is done which includes EDTA-treated blood, urine, blood culture specimens and any other specimens which may be requested by the attending physician. Facility adverse transfusion reaction reporting form, blood unit with compatibility tag attached, administration set and attached IV solutions are also requested for the post-examination. A set of blood culture samples are collected if a combination of symptoms is present. This may include fever, tachycardia, hypotension, chills, rigors, nausea, vomiting, diarrhea, dyspnea, oliguria, other signs of shock or a high suspicion of bacterial contamination without sign/symptom presentation. At the laboratory, they perform clerical check on the compatibility tag attached to donor unit while ensuring that the blood types of the donor unit and recipient are matched. They also make sure that the recipient’s name and unique identification number on the pretransfusion specimen, requisition and worksheet match exactly with the name and unique identification number on the compatibility tag. Afterwhich, they proceed in confirming the proper labeling of the post-transfusion samples. Performing visual check also helps in the identification of hemolysis. If hemolysis is present, a second sample must be obtained. Direct Antiglobulin Test (DAT) is performed on post-transfusion using EDTA-treated blood. This aids in the identification of conditions in which antibodies become attached to RBCs, causing them to hemolyze. If found positive, the sample is tested using monospecific IgG and C3 reagents. Elution is then performed once found positive using the monospecific IgG and C3 reagents. Elution aims to dissociate any antibody that is attached to the RBC surface. The next step to be done is ABO/Rh typing to both pre and post-transfusion samples of the patient. Donor blood unit is also tested for ABO/Rh typing. Any discrepancy observed is immediately reported to the Transfusion Medicine Supervisor. Indirect Antiglobulin Test (IAT) is another procedure being performed on the pre and post-transfusion samples of the patient. If found positive, perform and antibody identification. In cases an antibody is identified, they use phenotyping to the transfused unit/s for the corresponding antigen. The last step is the Anti-Human Globulin (AHG) crossmatch on donor unit/s using the pre and post-transfusion samples. Most clinically significant antibodies will react in this phase. The result of the investigation is entered into the LIS and the attending physician or nurse are notified. Documentation details of date, time and the name of the person notified are kept.The Royal Children’s Hospital MelbourneAustraliaA similar process goes is done in Australia, although not exactly the same and detailed as the one in Canada, a process is still done in the event of adverse transfusion reactions. Discontinuation of the transfusion is the first thing to do if an adverse reaction is suspected. Physical assessment of the patient including checking of the vital signs is done next. Venous access must be maintained using normal saline while the patient is being assessed which includes the patient’s airway, breathing and circulation. Blood bag unit is then verified if it really matches the patient’s details while ensuring that the patient is given due treatment regarding the matter. Notification of involved personnel such as the blood bank scientist, hematologist and others is done in order to give a heads up to the current situation. In their EMR blood flowsheet, they choose ‘yes’ to suspected transfusion reaction stating the actions taken after the transfusion reaction. Document of patient and blood product ID rechecked, signs and symptoms observed, management and investigation process are all recorded and the responsible persons are notified. Any post-transfusion samples collected and blood unit transfused are returned to blood bank for further testing.ConclusionAcute transfusion reactions are culpable for causing most serious adverse reactions or events. Proper education about different clinical manifestations of acute transfusion reactions with the competence to assess serious reactions on time can point to a better diagnosis. Standard operating procedure that contains the necessary information for the documentation, evaluation, reporting and follow-up of adverse reactions must be establish and adhered to in every institution. In this note, prompt investigation can be done to determine and eventually avoid the root cause of the unwanted event.References:Al-Riyami, A., Al-Hashmi, S., Al-Arimi, Z., Wadsworth, L., Al-Rawas, A., Al-Khabori, M. and Daar, S. (2014). Recognition, Investigation and Management of Acute Transfusion Reactions. Oman, pp.307, 316. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4117654/ [Accessed 18 Jul. 2019].Harris, J. and Crookston, K. (2019). Blood Product Safety. [ebook] New Mexico, USA. 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