Blood transfusion reactions

Detaield aggregation of notes about blood transfusion reactions in human body along with the precations and management.

1. Blood Transfusion Reactions By : Mohammed Al- Shalfi Dental School – Ibb University

2. Outline :  What is a blood transfusion ? What is blood transfusion reactions ? Causes of acute complications of transfusion . Blood transfusion reaction symptoms . Investigation . Blood transfusion reaction treatment and management . Delayed complications of transfusion . Surveillance and reporting .. Massive transfusion Case Study

3. Summary :  Blood transfusions can be life-saving in the appropriate setting. The vast majority of transfusions are completed without incident, but every transfusion recipient is at risk of a variety of adverse events (termed transfusion reactions) that can occur during, shortly after or long after the transfusion. Most transfusion reactions are diagnosed by exclusion; thus, any significant change in a patient's condition during transfusion should prompt an investigation. Successful investigation of a transfusion reaction depends on detailed observation, documentation and reporting of the patient's vital signs, before and after the transfusion, and the signs and symptoms that prompted the investigation.

4. What is a blood transfusion ? (1) Blood transfusions are most commonly done for blood components, such as red blood cells, platelets, or plasma. Before a blood transfusion, a medical provider will draw your blood. This sample will be sent to a laboratory for typing and crossmatching. Typing is when the lab determines blood type. Crossmatching is testing to determine if your blood is compatible with a donor’s blood of the same type. Knowing your blood type is important because red blood cells contain antigens, or protein markers, corresponding to these blood types. If a laboratory gives you the wrong type of blood, your immune system will detect any foreign proteins on the red blood cells of the wrong blood type and attempt to destroy them. Blood banks have thorough testing processes to make sure blood is safe and correctly typed for use. A doctor or nurse will explain any risks of blood transfusions to you and will closely monitor you while you’re receiving the blood.

5. What is a blood transfusion ? (2) Blood transfusion can be life-saving and provides great clinical benefit to many patients but it is not without risks [ : Immunological complications. Errors and 'wrong blood' episodes - the Serious Hazards of Transfusion (SHOT) report for the UK documented that an error incidence of 2,623 of just over 2 million components transfused in 2020 . Infections (bacterial, viral, possibly prion). Immunomodulation. Litigation. Growing awareness of avoidable risk, and improved reporting systems, have led to a culture of better safety procedures as well as steps to minimize the use of transfusion. The reporting rate of transfusion errors is improving although un-reporting of some serious adverse reactions still occasionally occurs. Alternative approaches to patient management should be used to reduce or eliminate the need for transfusion whenever possible

6. What is blood transfusion reactions ? Transfusion reactions are defined as adverse events associated with the transfusion of whole blood or one of its components. These may range in severity from minor to life-threatening. Reactions can occur during the transfusion (acute transfusion reactions) or days to weeks later (delayed transfusion reactions) and may be immunologic or non-immunologic. A reaction may be difficult to diagnose as it can present with non-specific, often overlapping symptoms. 

7. Causes of acute complications of transfusion (1) Acute haemolytic transfusion reaction Incompatible transfused red cells react with the patient's own anti-A or anti-B antibodies or other alloantibodies ( eg , anti-rhesus (Rh) D, RhE , Rhc and Kell) to red cell antigens. Complement can be activated and may lead to disseminated intravascular coagulation (DIC). Infusion of ABO incompatible blood almost always arises from errors in labelling sample tubes/request forms or from inadequate checks at the time of transfusion. Where red cells are mistakenly administered, there is about a 1 in 3 risk of ABO incompatibility and 10% mortality with the severest reaction seen in a group O individual receiving group A red cells. Non-ABO red cell antibody haemolytic reactions tend to be less severe but the Kidd and Duffy antigens also activate complement and can cause severe intravascular haemolysis .

8. Causes of acute complications of transfusion (2) Infective shock Bacterial contamination of a blood component is a rare but severe and sometimes fatal cause of transfusion reactions. Acute onset of hypertension or hypotension, rigors and collapse rapidly follows the transfusion. No UK cases of bacterial contamination of blood products were confirmed by SHOT in 2020. Platelets are more likely to be associated with bacterial contamination than red cells, as they are stored at a higher temperature.

9. Causes of acute complications of transfusion (3) Transfusion-related acute lung injury (TRALI) TRALI is a form of acute respiratory distress due to donor plasma containing antibodies against the patient's leukocytes. Transfusion is followed within six hours of transfusion by the development of prominent nonproductive cough, breathlessness, hypoxia and frothy sputum. Fever and rigors may be present. CXR shows multiple perihilar nodules with infiltration of the lower lung fields. Implicated donors are usually multiparous women (who are more likely to have become  alloimmunised ) and should be removed from the blood panel where possible. Gas exchange was significantly worse after transfusion of female but not male donor blood products in one study of high plasma volume transfusions in the critically ill.

10. Causes of acute complications of transfusion (4) Fluid overload Fluid overload occurs when too much fluid is transfused or too quickly, leading to pulmonary oedema and acute respiratory failure. Patients at particular risk are those with chronic anaemia who are normovolaemic or hypervolaemic and those with symptoms of cardiac failure prior to transfusion. These patients should receive packed cells rather than whole blood via slow transfusion, with diuretics if required. 

11. Causes of acute complications of transfusion (5) Fevers (>1°C above baseline) and rigors may develop during red cell or platelet transfusion due to patient antibodies to transfused white cells. This type of reaction affects 1-2% of patients. Multiparous women and those who have received multiple previous transfusions are most at risk. Reactions are unpleasant but not life-threatening. Usually symptoms develop towards the end of a transfusion or in the subsequent two hours. Most febrile reactions can be managed by slowing or stopping the transfusion and giving paracetamol.

12. Causes of acute complications of transfusion (6) Severe allergic reaction or anaphylaxis Allergic reactions occur when patients have antibodies that react with proteins in transfused blood components. Anaphylaxis  occurs where an individual has previously been  sensitised  to an allergen present in the blood and, on re-exposure, releases immunoglobulin E ( IgE ) or IgG antibodies. Patients with anaphylaxis become acutely  dyspnoeic  due to bronchospasm and laryngeal oedema and may complain of chest pain, abdominal pain and nausea. Individuals with severe IgA deficiency may develop antibody to IgA and, with repeated transfusion, are at high risk of allergic reaction. Urticaria and itching are common within minutes of starting a transfusion. Symptoms are usually controlled by slowing the transfusion and giving antihistamine, and the transfusion may be continued if there is no progression at 30 minutes. Pre-treatment with chlorphenamine should be given when a patient has experienced repeated allergic reactions to transfusion.

13. Blood transfusion reaction symptoms . Symptoms Feeling of apprehension or 'something wrong'. Flushing. Chills. Pain at the puncture site. Myalgia. Nausea. Pain in the abdomen, flank or chest. Shortness of breath. Signs Fever (rise of 1.5°C or more) and rigors. Hypotension or hypertension. Tachycardia. Respiratory distress. Oozing from wounds or puncture sites. Haemoglobinaemia . Haemoglobinuria .

14. Investigation Initial treatment of acute transfusion reactions (ATRs) should be directed by symptoms and signs. Treatment of severe reactions should not be delayed until the results of investigations are available. In all moderate and severe transfusion reactions, standard investigations, including FBC, renal and liver function tests and assessment of the urine for haemoglobin , should be performed. Patients who have experienced moderate or severe allergic reactions should have IgA levels measured. If the patient is dyspnoeic , obtain blood gases, CXR and central venous pressure (CVP) reading. Where TRALI is suspected, send anti-leukocyte antibody investigations.

15. Blood transfusion reaction treatment and management (1) All patients should be transfused in clinical areas where they can be directly observed and where staff are trained in the administration of blood components and the management of transfused patients, including the emergency treatment of anaphylaxis. Patients should be asked to report symptoms which develop within 24 hours of completion of the transfusion. If a patient being transfused for haemorrhage develops hypotension, a careful clinical risk assessment is required. If the hypotension is caused by haemorrhage , continuation of the transfusion may be life-saving. However, if the blood component is considered the most likely cause of hypotension, the transfusion must be stopped or switched to an alternative component and appropriate management and investigation commenced. Where the only feature is a rise in temperature of <1.5°C from baseline or urticaria, recheck that the correct blood is being transfused, give paracetamol and antihistamine, reset the transfusion at a slower rate and observe more frequently.

16. Blood transfusion reaction treatment and  management (2) Where the reaction is more severe: Stop the transfusion and call a doctor urgently to review the patient. Vital signs (temperature, BP, pulse, respiratory rate, O 2  saturation levels or blood gases) and respiratory status ( dyspnoea , tachypnoea, wheeze and cyanosis) should be checked and recorded. Check the patient's identity and recheck against details on blood unit and compatability label or tag.

17. Blood transfusion reaction treatment and management (3) Initial management where ABO incompatibility is suspected is to: Keep the intravenous (IV) line open with saline. Give oxygen and fluid support. Monitor urine output, usually following catheterisation . Maintain urine output at more than 100 ml/hour, giving furosemide if this falls. Consider inotrope support if hypotension is prolonged. Treat DIC appropriately - seek expert advice early and transfuse platelets/fresh frozen plasma (FFP) guided by the coagulation screen and bleeding status. Inform the hospital transfusion department immediately.

18. Blood transfusion reaction treatment and management (4) Where another haemolytic reaction or bacterial infection of blood unit is suspected: Send haematological and microbiological investigations as outlined above. General supportive management is as for ABO incompatibility. Start broad-spectrum antibiotics if bacterial infection is considered likely. If expert microbiological advice is not immediately available, current guidance is to follow local neutropenic sepsis protocols. Involve haematology and intensive care at an early stage.

19. Blood transfusion reaction treatment and management (5) Where anaphylaxis or severe allergic reaction is suspected: Adrenaline (epinephrine) 0.5-1 mg intramuscularly (IM) and repeat every 10 minutes until improvement occurs. High-flow oxygen. IV fluids. Nebulised salbutamol by face mask if required. Steroids are second-line and antihistamines are third-line treatments. IV antihistamines should be used very cautiously as they may further lower blood pressure. NB : call the anaesthetist if there is difficulty maintaining the airway.

20. Blood transfusion reaction treatment and management (6) Where TRALI is suspected: Seek expert help. Give high-concentration oxygen, IV fluids and inotropes (as for acute respiratory distress syndrome). Monitor blood gases, serial CXR and CVP/pulmonary capillary pressure. Ventilation may be urgently required - discuss with ICU. TRALI improves over 2-4 days in over 80% cases with adequate ITU management and respiratory support. Where fluid overload is suspected: Give furosemide IV and high-concentration oxygen.

21. Delayed complications of transfusion In those who have previously been immunized to a red cell antigen during pregnancy or by transfusion, the level of antibody to the blood group antigen may be so low as to be undetectable in the pre-transfusion sample. However, after transfusion of red cells bearing that antigen, a rapid, secondary immune response raises the antibody level drastically, leading to the rapid destruction of transfused cells. 5-10 days post-transfusion, patients present with fever, falling Hb (or unexpectedly poor rise in Hb), jaundice and hemoglobinuria. A rise in bilirubin and positive DAT will also be present.

22. Surveillance and reporting All suspected transfusion reactions should be reported immediately to the local hospital transfusion department in case blood packs have been accidentally transposed and another patient is at immediate risk. Transfusion reactions should be prominently recorded in the patient's clinical notes. All transfusion reactions should be reviewed by the hospital's transfusion committee.

23. Massive Transfusion Various definitions of massive blood transfusion (MBT) have been published in the medical literature such as: Replacement of one entire blood volume within 24 h Transfusion of >10 units of packed red blood cells (PRBCs) in 24 h Transfusion of >20 units of PRBCs in 24 h Transfusion of >4 units of PRBCs in 1 h when on-going need is foreseeable Replacement of 50% of total blood volume (TBV) within 3 h.

24. Case Study (1) A 78-year-old woman with anemia and congestive heart failure received 200 mL of red blood cells over a 30-minute period before tachypnea developed and she began complaining of dyspnea and mild chest pain. The transfusion was immediately stopped. The patient did not have fever or chills. Rales and crackles were heard in both lung fields, jugular venous distention was apparent and hypertension was noted. A chest radiograph showed cardiogenic pulmonary edema. The results of a blood-bank investigation for hemolysis were negative. Her symptoms were relieved when a diuretic was administered and 1 L fluid was voided.

25. Case Study (2) This clinical scenario is typical of transfusion-associated circulatory overload, which is underreported and should be suspected when a patient at risk of volume overload (e.g., heart, lung or kidney failure) complains of dyspnea or demonstrates signs of respiratory distress. The treatment of transfusion-associated circulatory overload includes supplemental oxygen and diuretics.

26. Case Study (3) Although much less common than transfusion-associated circulatory overload, transfusion-related acute lung injury (TRALI) may present in a similar manner. Transfusion-related acute lung injury can be differentiated by the typical chest radiograph findings of noncardiogenic pulmonary edema and by the absence of jugular venous distension and normal right-atrial pressure. Brain (b-type) natriuretic peptide is normally used to help diagnose the presence and severity of heart failure. However, in a transfusion setting, elevated post transfusion levels are suggestive of transfusion-associated circulatory overload and maintenance of pre-transfusion levels is suggestive of transfusion-related acute lung injury. This test may be used as a marker to help to distinguish between these 2 types of reactions, although this test is not yet available at all hospitals.