BLOOD TRANSFUSION REACTIONS Adverse effects associated with transfusion of whole blood or blood components inspite of all relevant laboratory tests Minor – life threatening Transfusion reactions may be acute or delayed: - Acute transfusion reaction (within 24 hours) - Delayed transfusion reaction (> 24 hr upto months and years)
INTRAVASCULAR TRANSFUSION REACTIONS Hemolysis within the circulatory system Mediated by IgM antibodies Rapid activation of complement and is usually associated with the transfusion of ABO incompatible blood Acute Hemolytic Transfusion Reaction(AHTR) Symptoms and signs - Burning sensation at the site of infusion, Flushing and fever, Chills , Pain in the back, Shortness of breath, Hypotension/ shock, DIC, Acute renal failure
EXTRAVASCULAR TRANSFUSION REACTIONS Hemolysis by macrophages in the spleen and liver IgG mediated red cell destruction following Rh , Kell or Duffy system Delayed Hemolytic Transfusion Reaction(DHTR) Clinical evidence is much delayed - Primary alloimmunisation - after couple of weeks, Rh or Kell - Anamnestic or secondary response - already sensitized RBCs Signs - Fever, Anemia, Jaundice, Hemoglobinuria (rare)
CAUSES OF HEMOLYTIC TRANSFUSION REACTIONS Clerical errors - Inadequate & incorrect labelling - Improper identification of patient - Incorrect interpretation of test results Technical errors - Errors in blood grouping - Improper cross matching technique - Failure to detect weak antibodies Non Immune causes like bacterial contamination, chemically or thermally hemolysed units
MEASURES TO BE TAKEN Stop transfusion Keep the I.V. line open for saline Inform the attending clinician and blood bank Recheck labels , forms and identity Send following samples to blood bank Immediate post transfusion clotted sample and EDTA sample Implicated blood bag and transfusion set First voided urine
Supportive care; ABC +/-pressors Cardiac monitoring because of risk of hyperkalemia Infuse NS to maintain BP and promote diuresis Avoid RL and dextrose because calcium in RL will promote clotting in IV line and dextrose will increase hemolysis. Maintain urine output >100-200ml/hour With DIC early heparinization may be beneficial
STOP THE TRANSFUSION PERFORM CLERICAL CHECK AND DRAW POST-Tx SAMPLE Hemoglobinemia DAT ABO/Rh Testing If Suspicious Consider Second Tier Testing Haptoglobin LDH Crossmatch Bilirubin Urine Hgb TIER 1 TIER 2
1) Check documents Was the blood transfused to the intended recipient? Check labels on the patient & the blood components Was the correct unit tagged? Was the correct unit issued? Was the correct sample used for Testing? Rule out clerical error
2) Check for technical errors Errors in blood grouping of donor or recipient Improper technique used which lead to undetection of incompatibility Failure to detect weak antibodies
Pre and Post-transfusion EDTA sample- plasma inspected for free hemoglobin or increased bilirubin Pink or red discolouration seen if hemolysis has occurred in the past few hours – indicates presence of free Hb Deep red or brown/ yellowish if Hb metabolised to bilirubin in the sample drawn 6-8 hours after transfusion 3) Visible plasma hemoglobin
4) Group testing Forward and reverse grouping by Slide Tube Microplate Column agglutination/ gel technology Solid phase adherence technology Positive (+): small clumps seen floating in a clear liquid Negative (-): Uniform suspension.
Done on both pre and post transfusion samples DAT – Positivity indicates the presence of recipient antibodies on the donor red cells IAT - Antibodies in patients’s serum against donor RBCs, and also donor plasma against patient’s red cells 5) Direct and Indirect Antiglobulin Tests, Cross matching
OTHER INVESTIGATIONS Plasma haptoglobin level – will be decreased in intravascular hemolysis , but has to be compared with pretransfusion values Bilirubin and LDH – elevated in intravascular hemolysis Patients urine analysis for free hemoglobin and red cells Gram staining and culture of donor’s blood to rule out infection Peripheral smear Investigations for complications like DIC and Acute renal failure
PREVENTION AND CONTROL OF HEMOLYTIC TRANSFUSION REACTIONS Proper identification of patient when the sample is taken for pre- transfusion testing Proper labeling of drawn blood samples Proper identification of patient and the unit of blood at the time of transfusion Appropriate and sensitive techniques for compatibility testing Avoid unnecessary transfusions Close monitoring The time between the suspicion of transfusion reaction, investigations & treatment should be as short as possible Check evidence of contamination which are gross hemolysis or change in colour of blood
NON-HEMOLYTIC TRANSFUSION REACTIONS Febrile Non Hemolytic Transfusion Reactions (FNHTR) Urticarial (allergic) transfusion reactions Anaphylactic transfusion reactions Non cardiogenic pulmonary edema or TRALI Transfusion associated Circulatory overload (TACO) Graft versus host disease ( TA GVHD)
FEBRILE NONHEMOLYTIC TRANSFUSION REACTIONS Presence of any one or more Fever Chills and rigor Increase in temperature by 1 degree celsius or more , above the baseline temperature during or immediately after the transfusion without any other medical cause Most common transfusion reaction (>90%) Due to presence of antibodies against WBCs or platelet antigens in multitransfused or multiparous patients Occur within minutes of transfusion, self-limiting
FEBRILE NONHEMOLYTIC TRANSFUSION REACTIONS Signs and symptoms can mimic hemolytic Laboratory investigations:- No evidence of hemolysis No red/ Pink plasma DAT negative No increase in bilirubin No hemoglobinuria Prevention and control:- Leucocyte poor red cell transfusions Antipyretic therapy
URTICARIAL TRANSFUSION REACTIONS Allergic reactions due to patient’s preformed reagins reacting with transfused allergens or due to soluble substances in donor plasma Symptoms – Itching urticarial lesions Treatment -Temporary interruption, open IV line with NS - Antihistamines – Diphenhydramine 50 mg 1 hour before transfusion and at start of transfusion - Washed RBC can be used if premedication fails
ANAPHYLACTIC TRANSFUSION REACTIONS Severe life threatening In rare patients who are IgA deficient and have developed Anti IgA antibodies Reaction develops quickly within minutes of starting the transfusion- GI upset, angioedema , flushing, respiratory distress, hypotension, shock Treatment Stop transfusion Epinephrine 0.3 ml SC 1:1000 dilution- Alpha agonistic action Maintain blood pressure by crystalloid infusions
NONCARDIOGENIC PULMONARY EDEMA/ TRALI Transfusion related acute lung injury New episode of lung injury occuring within 6 hours of transfusion One of the leading causes of transfusion related mortality Endothelial damage caused by leucoaggregates in pulmonary microcirculation
Consensus Definition of TRALI 2004
Pathophysiology of TRALI Damage associated molecular patterns (DAMPs) Inflammation and damage of pulmonary microvasculature Sensed by Neutrophils , platelets, endothelial cells and macrophages, results in activation Processing of blood/components Storage of blood/ components Generate and release On transfusion Release enzymes, proteins, ROS Capillary leak Respiratory distress Pulmonary edema
Signs and symptoms Acute respiratory distress, Tightness of chest Dry cough, Nausea, Dizziness Fever & Chills, hypoxia, hypotension, tachycardia Copious frothy tracheal exudate in intubated patient X-ray – bilateral pulmonary infiltrates (Batwing Appearance) Management Stop transfusion, Keep I.V. line open, Inform the attending physician Methyl prednisolone 30 mg/kg every 6 hours for 48 hours Respiratory support
TRANSFUSION ASSOCIATED CIRCULATORY OVERLOAD (TACO) Excessive volume or high speed of transfusion of whole blood in severely anemic patients with compromised lung and cardiac functions, precipitating congestive heart failure Breathlessness, cough and distension of jugular veins, rapid increase in BP Elderly patients , infants and pregnant women in third trimester- more prone
Criteria Acute onset worsening respiratory distress during or within 12 hrs of transfusion With 2 or more of the following Evidence of acute respiratory distress Evidence of unanticipated cardiovascular changes Evidence of fluid overload responding to diuretic therapy Elevation in natriuretic peptide levels BNP > 1.5 times pretransfusion value
TACO Management In severly anemic patients it is advisable to give packed red cells Rate of infusion – 1ml / kg / hr Diuretic should be given before transfusion In severe cases exchange transfusion TRANSFUSION ASSOCIATED DYSPNOEA Respiratory distress within 24 hours of transfusion that does not meet the criteria for TRALI/ TACO or allergic reaction
GRAFT VERSUS HOST DISEASE Rare complication in patients with a compromised immune system Engrafted donor lymphocytes reacting against host antigen Usually arises 3-30 days after transfusion Patients at risk are Lymphopenic patients Bone marrow suppressed cases Fetus receiving intra-uterine transfusions Individuals with congenital immuno-deficiency syndromes Hemotologic and oncologic disorders Receiving blood components from blood relatives
3 prerequisites The graft blood should contain immunocompetent cells Antigenic difference between recipient and host The recipient should be sufficiently immunocompromised Presentation of host proteins by host APC to donor T cells Activation, proliferation and migration of T cells Damage of host tissues Fever, rash diarrhoea , liver dysfunction, bone marrow suppression, superinfections 3 phases Symptoms
Prevention Leucocyte irradiated blood component
TRANSFUSION SIDEROSIS Patients who receive repeated transfusions over a long period, eg : Thalassemia patients 200-250 mg elemental iron/ unit blood No effective mechanism to dispose excessive iron in the body Gets deposited in heart, liver, pancreas Management Iron chelating agents Neocyte transfusion can be given
PLATELET INCOMPATIBILITY Post transfusion purpura as a result of anamnestic production of platelet antibodies Rx High dose I/V immunoglobulin Corticosteroids Plasma exchange
BACTERIAL SEPSIS/CONTAMINATION Most commonly associated with Platelet Component because platelet is stored at 22-25 o C, others at lower temperature
BTR workup Stop transfusion Ask to sent the bag with attached tubings Draw immediate post transfusion blood from the other hand (before any DNS /NS ) First voided Urine sample Clerical checks Check the color of Sample (any changes) Grouping & cross matching Microscopic analysis of hemolysis in pre (donors) and post transfusion Sample Biochemistry and microbiological evaluation