INVESTIGATION OF ADVERSE TRANSFUSION REACTIONS TABLE OF RECOMMENDED TESTS. Type of Reaction Presentation Recommended Tests Follow-up Tests

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Minor Allergic (Urticarial) Urticaria, pruritis, flushing, rash If skin reaction only and mild hives/ rash <2/3 body surface area no serological investigation required. Initiate ATR Investigation Profile if signs/symptoms worsen Febrile Non-hemolytic Fever (onset > 15 minutes into transfusion), chills, rigors, headache, nausea, vomiting, malaise NB: Fever not always present If the only sign/symptom is a temperature 38 C and <39 C and >1 C above baseline. No serological investigation is required. Initiate ATR Investigation Profile if signs/symptoms worsen Acute Hemolytic Fever, chills, rigors, hemoglobinuria, hypotension, renal failure with oliguria, DIC, back/ flank pain, pain along infusion vein, anxiety, tachycardia. Renal failure may occur. Antibody Identification panel, elution (other tests as required) Phenotyping of recipient, if required Phenotyping of transfused units LDH

Haptoglobin Plasma hemoglobin Urine for free hemoglobin and hemosiderin CBC, platelet count, reticulocyte count, peripheral smear for spherocytes INR/ PTT, D-Dimer, fibrinogen BUN, creatinine Severe Allergic/ Anaphylactic/ Anaphylactoid Bacterial Contamination Urticaria, pruritis, flushing, erythema, anxiety, rash (> 2/3 of body area), hypotension, nausea, vomiting, respiratory distress, dyspnea, laryngeal/ pharyngeal edema, bronchospasm, substernal pain, shock, loss of consciousness, cardiac arrhythmia Fever AND any of the following signs/ symptoms: nausea, vomiting, diarrhea, chills, rigors, DIC, tachycardia, shock, hypotension, SOB, circulatory collapse OR Fever (temperature 39 C and a change of Quantitative serum IgA levels Consider testing for IgA antibodies if the serum IgA levels are less than 0.05 mg/dl. (performed by Canadian Blood Services Reference Laboratory) Bacterial identification Endotoxin testing Antibiotic susceptibility testing Molecular testing Serotyping

1 C from pretransfusion value) WITHOUT other signs/ symptoms OR Fever that does not respond to antipyretics OR A high suspicion of sepsis without fever NB: If bacterial contamination is suspected, an investigation should be conducted even if the above criteria have not been met. Transfusion Related Acute Lung Injury (TRALI)/ Possible TRALI Acute respiratory distress, hypoxemia, chills, fever, cyanosis, hypotension, nonproductive cough, tachycardia, noncardiogenic bilateral pulmonary edema WBC antibody screen (donor and recipient) HLA typing of recipient ( These tests are performed by the Canadian Blood Services Reference Laboratory) Transfusion Associated Dyspnea (TAD) Respiratory distress within 24 hours of transfusion

Transfusion Associated Circulatory Overload (TACO) Hypotensive Post Transfusion Purpura (PTP) Dyspnea, orthopnea, tachycardia, hypertension, headache, cyanosis, productive cough with pink frothy sputum Abrupt onset of hypotension ( 30 mmhg) with or without bradycardia, nausea, dyspnea, urticaria, flushing Profound thrombocytopenia (usually <10 x 10 9 /L), purpura, petechiae, bleeding may be accompanied by chills, rigors, fever, bronchospasm CBC Platelet count Platelet antigen typing Anti-platelet antibody specificity (The above tests are performed by Canadian Blood Services Reference Laboratory) Investigations to rule out other causes of thrombocytopenia Delayed Hemolytic Jaundice, fever, unexplained fall in posttransfusion haemoglobin, weakness, malaise, fatigue, hemoglobinuria, renal failure may occur. Antibody Identification panel, elution as required Phenotyping of recipient, if possible Phenotyping of transfused units if available

LDH Haptoglobin Plasma hemoglobin Urine urobilinogen CBC, reticulocyte count, peripheral smear for spherocytes INR/ PTT, D-Dimer, fibrinogen BUN, creatinine* Transfusion Associated Graft versus Host Disease Erythroderma, nausea, fever, maculopapular erythematous rash, anorexia, vomiting, diarrhea, hepatitis, pancytopenia, jaundice, elevated liver enzymes CBC Liver enzymes HLA typing of recipient blood and/ or tissue HLA typing of donor Skin biopsy Liver biopsy Bone marrow examination Iron Overload Delayed Serological Diabetes, cirrhosis, cardiomyopathy, pancreatic failure, arrhythmias Usually no physical signs or symptoms Detection of new alloantibody post transfusion with no evidence of hemolysis Serum ferritin Liver enzymes Endocrine function test Antibody Screen Antibody identification panel, elution as required Phenotyping of recipient, if possible Phenotyping of transfused units, if available

Sickle Cell Hemolytic Transfusion Reaction/ Hyperhemolysis Syndrome Fever, post-transfusion haemoglobin lower than pre-transfusion value, reticulocytopenia, elevated LD and bilirubin over baseline, hemoglobinuria, back, leg or abdominal pain usually occurring within one week of transfusion ATR Investigation Profile Antibody Identification panel, elution as required Phenotyping of recipient, if possible Phenotyping of transfused units if available LDH Haptoglobin Plasma hemoglobin Urine urobilinogen CBC, reticulocyte count, peripheral smear for spherocytes INR/ PTT, D-Dimer, fibrinogen BUN, creatinine Hyperkalemia Cardiac arrhythmias Hypocalcemia Air Embolism Hypothermia Parasthesis, tetany, arrhythmia Sudden onset severe hypotension, SOB, cyanosis, collapse Decreased core body temperature, cardiac arrhythmias, coagulopathy, platelet dysfunction