Blood Transfusion Reactions

How will you define a blood transfusion reaction?

1. Most of the blood donations proceed without any complications.
2. Occasionally, a donor may have adverse effects on the donation.
3. Blood transfusion reactions are defined as any adverse events resulting from the transfusion of blood or blood components.

How will you summarize the blood transfusion reactions?

Type of reaction	Clinical presentation of the reaction
Recipient reaction to donor antigens (These antigens are present on donor cells)	Allergic reaction Anaphylactic reaction Hemolytic reaction Nonhemolytic febrile reaction Leukoagglutinin reaction Pyogenic reaction Tissue-organ immunologic reaction Cytopenic reaction
Blood group antigens	Rh blood group system ABO system Minor blood groups Platelets antigens Histocompatibility leukocyte antigen (HLA) system
Infective agents	Hepatotropic viruses (HBV, HCV, HAV) Syphilis Malaria Cytomegaloviruses (CMV) Epstein-Barr virus (EBV) HIV-1 and HIV-2
Other chemical issues	Hyperkalemia Citrate overload Transfused blood temperature Donor medication Depletion of platelets Depletion of coagulation factors

Types of reactions in the donors:

What are the types of reaction in the Donor (due to blood donation)?

1. Most of the donations proceed without any reaction. The reactions are:
   1. Vasovagal reactions.
   2. Some may have a psychological influence on the sight of blood.
   3. Neurophysiological response to actual blood donation.
   4. These reactions are divided according to the severity:
      1. Mild reactions.
      2. Moderate reactions.
      3. Severe reactions.

How will you discuss the mild reaction in the donor?

1. Mild reactions are the most common reactions; most donors will have signs and symptoms of shock, but do not lose consciousness.
2. Mostly, these are the following reactions that may be seen in donors.
   1. Donors may have anxiety and nervousness.
   2. There may be pallor and sweating.
   3. Some donors may feel a sense of warmth.
   4. Some donors may experience hyperventilation (increased respiratory rate).
   5. Some donors may have an increased or thready pulse.
   6. There may be hypotension.
   7. Some donors develop nausea and vomiting.

3. How will you treat mild donor reactions?
   1. The best course of action is to stop the donation immediately.
   2. Remove the tourniquet and needle from the donor.
   3. In case of hyperventilation, ask the donor to breathe inside the bag, increasing the amount of CO2.
   4. Loosen the clothes, particularly the clothes around the neck like a necktie.
   5. Raise the legs of the donor (45 degrees at least).

1. 6. Reassure the donor and decrease his anxiety or stress.
   7. Keep an eye on the donor until they are fully recovered.

How will you discuss the moderate reaction in the donor?

1. These signs and symptoms are like mild donor reactions, but the donor will lose consciousness.
2. There will also be side effects of the mild reactions.
3. Donors will have unconscious attacks.
4. The pulse rate is low (decreased).
5. There will be rapid, shallow respiration and hyperventilation.
6. There will be hypotension, and the blood pressure may be as low as 60 mm Hg.
7. How will you treat the moderate reactions?
   1. Take all the measures done in the mild reaction.
   2. Check BP, pulse, and respiration until these become normal.
   3. Give 95% oxygen and 5% CO2.
   4. Take the donor to a separate area so that other donors may not experience the same side effects.

How will you discuss the severe reaction in the donor?

1. These are different from the above due to the presence of convulsions. However, there will be the presence of mild and moderate symptoms and signs.
2. The convulsions (seizures) are caused by cerebral ischemia associated with vasovagal syncope.
3. Vasovagal ischemia is due to:
   1. Reduced blood flow to the brain due to deepening shock symptoms.
   2. Marked hyperventilation.
   3. Severe CO2 depletion can cause convulsions or tetany.
4. Other severe signs and symptoms are:
   1. There is tetany due to hyperventilation.
   2. The donor may have stiffness or tingling in the fingers.
   3. The symptoms may increase and become pronounced convulsions if the CO2 intake increases.
   4. Fingers and thumbs may have spasms.
   5. Mild convulsions:
      1. The voice will fade out.
      2. There is a short lapse of consciousness.
      3. There will be involuntary movements of the arms and legs.
   6. Severe convulsions:
      1. Donors will have rigid bodies and tightly clenched teeth.
      2. There will be slight involuntary movements of the arms and the legs.
      3. The donor may experience temporary loss of breathing, followed by rapid breathing.

5. How to treat the severe donor reactions?
   1. Ask the donor to breathe into the airbag.
   2. Try to prevent any injury to the donor during convulsions.
   3. Ensure adequate airways.
   4. Give 95% Oxygen and 5% CO2.
   5. Get a consultation from a medical doctor.
   6. If the donor develops cardiopulmonary problems, call for medical assistance immediately.
   7. In case of cardiac arrest, start cardiopulmonary resuscitation until medical help arrives.

What are the Blood transfusion reactions in the recipient?

1. Since no two individuals possess the same antigens on their RBCs, except in identical twins, there is always a risk of developing alloantibodies in the recipients.
2. When alloimmunization occurs due to blood transfusion, it will have harmful consequences in future transfusions and pregnancy.
3. The reactions of the recipient are:
   1. Urticaria is an allergic reaction.
   2. Anaphylactic type I hypersensitivity reaction.
   3. Febrile reactions.
   4. Hemolytic reactions.
   5. Infection due to a contaminated blood transfusion.
   6. Transmission of diseases like syphilis, malaria, viral hepatitis, and HIV.

Type of blood transfusion reaction in the recipient:

Acute reaction:

1. This occurs within minutes to 24 hours of the transfusion.

Delayed reaction:

1. These may develop in days to months to even years after the transfusion.

What are the signs and symptoms of a blood transfusion reaction in the recipient?

1. Continuously monitor the recipient for any of the following signs and symptoms, which may indicate the onset of a blood reaction.
2. An early sign may be allergic in the form of itching and hives.
3. Fever. The patient’s temperature increases by 1°C, with only minor changes in other vital signs.
   1. Chills
   2. Nausea and vomiting.
4. Chest, abdomen, or flank pain.
5. Back pain.
6. Hypotension or hypertension.
7. The patient may go into shock.
8. The feeling of heat along the vein where the blood is transfused.
9. The feeling of constriction in the chest.
10. Facial flushing.
11. Hemoglobinuria.
12. Oliguria.
13. Dyspnea.
14. Oozing blood from the wound.
15. Anemia.

• Therefore, the patient may exhibit any of the above findings in the event of a blood transfusion reaction.

How will you work up the blood transfusion reaction in the recipient?

What are the types of blood transfusion reactions in the recipient?

1. Acute blood transfusion reaction in the recipient:
   1. This reaction occurs within 24 hours.
   2. Acute reactions are more severe than delayed reactions.
   3. Acute reactions accompany a fever, nausea, vomiting, hypotension, back pain, and substernal pressure.
   4. There is hemolysis, and it is generally intravascular.
   5. Hemoglobin released from the RBCs may give rise to hemoglobinemia (red plasma rather than yellow plasma)  and hemoglobinuria (red urine that remains red even after centrifugation).
   6. There is impaired renal function.
2. A delayed blood transfusion reaction occurs in 5 to 7 days. This may vary from 3 to 21 days.
   1. This occurs in two conditions:
      1. A primary immune response, accompanied by an increase in antibody concentration, leads to hemolysis.
      2. When the patient is sensitized by exposure to the alloantigen in a previous blood transfusion or pregnancy.
   2. Antibodies to Kidd and Rh antigens are responsible.
   3. Hemolysis is typically extravascular; the only evidence is a decrease in hemoglobin and an increase in bilirubin.
   4. The patient may have a low fever and feel malaise.
   5. When no hemolysis is found in a delayed reaction, it is called a serologic reaction rather than hemolytic.

How would you describe a febrile non-hemolytictransfusion reaction in the recipient?

1. These are common complications seen in patients with multiple blood transfusions.
2. These are related to anti-leucocyte antibodies present in the recipient’s blood.
   1. These antibodies react with the WBC.
3. Another possibility is the presence of cytokines released by the lymphocytes in the donated plasma during storage.
4. There is an increase in body temperature of 1°C or more.
   1. This is accompanied by chills, rigors, and generalized discomfort.
   2. Some patients may have nausea and vomiting.
5. This occurs shortly after the transfusion, usually within 1 to 2 hours.
6. Mostly, these reactions are mild and persist for no more than 8 hours.
7. Antipyretics and meperidine treat these for rigors.

How would you discuss the Transfusion-related acute lung injury in the recipient?

1. This complication occurs during or within 6 hours after transfusion completion.
2. The cause of this complication is the presence of anti-leucocyte antibodies in the donor’s plasma.
3. The immune complexes are trapped in the pulmonary vasculature, leading to alveolar edema.
4. This is characterized by:
   1. Acute respiratory distress.
   2. Hypoxia.
   3. Bilateral infiltrates on chest X-ray.
   4. There is a fever.
   5. There is hypotension.
5. These patients recover through supportive measures.
   1. But overall mortality is 5%.

How would you discuss the transfusion-associated graft-versus-host reaction?

1.  Immunocompetent T-lymphocytes in the cellular components may elicit a reaction.
2. These T-lymphocytes can react in the skin and gastrointestinal tract, as well as to cells in the bone marrow.
3. This reaction is usually fatal.
4. These T-lymphocytes in the blood components can be inactivated by exposure to gamma radiation. This treatment is very effective.
5. The patients who are prone to these complications are:
   1. Hematopoietic stem cell transplantation.
   2. Hematological Malignancies.
   3. Infants born with hemolytic disease of the newborn.
   4. Infants with low birth weight.
   5. The fetus receives an intrauterine blood transfusion.

How would you discuss the post-transfusion purpura in the recipient?

1. This rare complication occurs in patients who lack common platelet antigens.
2. These patients develop antibodies from previous blood transfusions or pregnancy.
3. These patients develop an anamnestic reaction and become severely thrombocytopenic.
4. This reaction usually takes 7 to 10 days.
5. The reaction is self-limiting, but it may sometimes be complicated by severe hemorrhage.
6. It can be managed by steroids and immunoglobulins.

What is the Refractoriness to platelet transfusion?

1. Patients may become sensitized to leucocytes and platelet antigens through previous blood transfusions or pregnancy.
2. Platelets are cleared immediately from the circulation when preformed antibodies are present.
3. The reaction is against the foreign platelets’ antigen or HLA-class 1 molecule (expressed on the platelets’ membranes).
4. Evaluating the platelet count in these patients becomes challenging.

What is the reaction to plasma components?

1. 1% to 3% of patients may have an allergic reaction to the blood products.
2. This is the host’s reaction to the donor’s plasma proteins.
3. The majority of these reactions show:
   1. Hives.
   2. Pruritis.
   3. Erythema.
   4. Steroids or antihistamines can treat it.
4. Serious reactions are less frequent, like:
   1. Bronchospasm.
   2. Laryngeal edema.
   3. GIT symptoms like nausea, vomiting, abdominal cramps, and diarrhea.
   4. Hypotension due to type 1 anaphylaxis.
   5. Patients with IgA deficiency need components from the IgA-deficient donor, or can use their own components.

What are the etiological signs and symptoms of blood transfusion reactions in the recipient?

1. Circulatory overload shows:
   1. Shortness of breath.
   2. Direct Coombs’ test is negative.
   3. There is no fever or chills.
2. Acute hemolytic transfusion reaction shows:
   1. Fever and chills.
   2. There are fever and chills.
   3. Hemoglobin is low.
   4. There is hemoglobinuria.
   5. There may be hypotension and shock.
   6. Direct Coombs’ test is positive.
3. Febrile non-hemolytic transfusion reaction:
   1. There are fever and chills.
   2. There are nausea and vomiting.
   3. There may be shortness of breath.
   4. Direct Coombs’ test is negative.
4. Transfusion-related acute lung injury:
   1. There are fever and chills.
   2. There is shortness of breath.
   3. There are hypotension and shock.
   4. Direct Coombs’ test is negative.
5. Bacterial contamination of the blood:
   1. There are fever and chills.
   2. Hemoglobin is low.
   3. There may be hemoglobinuria.
   4. There are hypotension and shock.
   5. Direct Coombs’ test is negative.

What are the non-immunologic reactions in the recipient?

1. Hypothermia:
   1. It usually occurs when cold blood is transfused.
   2. There may be minor discomfort.
   3. This may also occur in a massive blood transfusion, where the blood is stored at 1°C to 10 °C.
   4. Hemostasis is affected when the circulating blood is below 37 °C.
   5. In extreme cases, cardiac dysrhythmias may occur and cause cardiac arrest.
   6. The use of a high-throughput blood warmer is needed.
2. Transfusion-associated circulatory overload:
   1. Volume overload is a common and often overlooked complication of blood transfusion.
   2. The following group of patients is at risk:
      1. Patient with congestive heart failure.
      2. Patient with renal failure.
      3. Very young and old patients.
   3. These patients have signs and symptoms:
      1. There is dyspnea.
      2. There is orthopnea.
      3. Cough and chest pain.
      4. During or soon after the transfusion, there is hypoxia, rales, tachycardia, or hypertension.
   4. The patient can be treated with supplemental oxygen and diuresis.
      1. If another blood transfusion is required, administer the blood slowly and consider adding diuretics.

What are the Chemical complications in the recipient?

1. Iron-overload:
   1. Each unit of blood contains around 200 mg of iron.
   2. Repeated blood transfusion leads to the deposition of iron in various tissues.
   3. In case a patient has received around 100 bottles or more of blood transfusions, then the patient may have complications like:
      1. Cardiac Arrhythmias.
      2. Pancreatic failure and bronze diabetes.
      3. Liver function abnormality.
      4. Iron overload can be treated by chelating agents such as desferrioxamine or deferasirox.
      5. This should be started in the early stage before the deposition of iron.
2. Potassium – Toxicity:
   1. Potassium leaks out of the RBCs during storage due to a decrease in the ATP level.
   2. ATPase-dependent Na⁺/K⁺ pump activity decreases.
   3. Each blood RBC unit contains as much as 6 mmol of extracellular K⁺ when an outdated sample is used.
   4. Extra K+ may lead to cardiac arrhythmias.
   5. Washing the RBCs may remove extra K⁺.
3. Citrate toxicity:
   1. Citrate is used as an anticoagulant.
   2. Citrate is present in the plasma.
   3. Citrate is metabolized by every nucleated cell of the body.
   4. In the case of massive blood transfusion, the rapid influx of citrate may not be metabolized by the body, leading to the accumulation of citrate in the patient’s plasma.
   5. The patient can receive up to one unit of fresh-frozen plasma every 6 minutes without evidence of citrate toxicity.
   6. Patients with liver diseases metabolize citrate slowly and are prone to develop citrate toxicity.
   7. The citrate chelates the calcium, causing the ionized calcium level to drop and leading to:
      1. Peri-oral tingling.
      2. Extremity paresthesia.
      3. There may be severe hypocalcemia  (ionized calcium) leading to cardiac dysrhythmias.
4. Depletion of 2, 3 Diphosphoglycerate:
   1. When blood is stored for a longer period, there is a decrease in the intracellular 2,3-diphosphoglycerate.
   2. This will result in a shift to the left of the oxygen-hemoglobin dissociation curve.
   3.  When the stored unit is transfused, it restores the 2,3-DPG over 24 to 48 hours.
   4. It is recommended that transfused blood to the neonates should be kept for less than a week.
   5. Complications are found in the neonates if older blood units are transfused.
   6. In the case of stored blood deficient in 2,3-DGP, it impairs oxygen delivery, particularly in neonates.

What are the infectious complications in the recipient?

1. Viral infections. There is a risk of infection by:
   1. Hepatitis B virus.
   2. Hepatitis C virus.
   3. HIV
2. Because donor education and screening have reduced the incidence.
3. The current significant pathogens, such as bacterial blood contamination, are a problem even in developed countries like the USA.
4. The bacteria that are more frequently found are:
   1. Yersinia enterocolitis.
   2. Pseudomonas.
   3. Enterobacter spp.
   4. Serratia sp.
5. Platelet units are reported to have an infection by:
   1. Gram-positive bacteria, cocci-like:
      1. Streptococcus.
      2. S.Epidermidis.
      3. Staphylococcus.
   2. Gram-negative bacteria reported are:
      1. Klebsiella spp.
      2. Serratia spp.
      3. Salmonella spp.
      4. Enterobacter spp.
6. The source of the infection may be contamination from the skin. The skin commensals are thought to be picked up and introduced into the bloodstream through venepuncture during blood donation.
7. Cytomegalovirus (CMV) can be transmitted through the transfer of blood components containing leukocytes, such as packed red blood cells (RBCs) and platelets.
   1. It can produce systemic infection by CMV in immune-compromised patients who are seronegative.
   2. The following groups are more prone to getting CMV infection:
      1. Premature infants with low birth weight (<1200 g).
      2. CMV-negative pregnant women receiving an intrauterine transfusion.
      3. CMV-negative, HIV-infected patients.
      4. CMV-negative recipient of or candidate for hematopoietic organ transplantation.
   3. To reduce the risk of CMV, recommend screening donors.
   4. Remove the leukocytes that contain latent CMV by filtration with leukocyte reduction filters.

How will you summarize blood transfusion-related reactions?

What is the risk of the various viruses’ transmission from the blood components?

Viruses	The estimated risk  of transmission from the blood components
HIV	1:493,000
HTLV	1:641,000
HBV	1:63,000
HCV	1:103,000
HAV	Rarely reported in some cases
West Nile virus	It may spread through the blood
Transmission during pregnancy:
HBV, HCV, HIV, CMV, HPV-B19	Rates vary from country to country
Dengue fever	In tropical and subtropical countries
Zika virus	May be transmitted to the fetus

What are the complications of blood transfusion reactions?

1. Anemia
2. Kidney failure.
3. Respiratory problems.
4. Ultimately shock.

What are the Common Causes of blood transfusion reactions?

1. The most common cause is faulty matching.
2. Improper identification or labeling of the donor and recipient may cause a transfusion reaction.

What are the problems seen in the ABO Blood Typing?

1. There may be abnormal, weak agglutination. Normally, there are 3⁺ to 4⁺ agglutinations.
2. Mixed-field agglutination occurs when some of the patient’s RBCs agglutinate, while others do not.
3. Rouleaux formation by RBCs should be differentiated from agglutination. In comparison, Rouleaux formation refers to the stacking of red blood cells (RBCs).
4. Clumping due to blood micro-clots in the procedure.
5. No agglutination when all cells and serum ABO is nonreactive.

What are the common mistakes in the ABO blood group typing?

1. If there are incorrect blood reagents,
2. If there is contamination of the reagents.
3. If incorrect or outdated reagents are used.
4. If you miss adding the reagents, the patient’s serum, or the patient’s cells.
5. Fail to follow the manufacturer’s instructions.
6. Over-centrifugation can lead to false-negative results.
7. If there is an incorrect incubation temperature.
8. If there is an improper ratio of the antisera or RBCs.
9. The clerical mistake of typing the result.
10. If there is contaminated glassware or supplies.
11. If there is a failure to identify the signs of hemolysis.
12. If there is weak agglutination.

Summary of the adverse effects of blood and blood products reactions:

What is the recipient’s reaction to donor antigens (donor RBCs)?

1. The recipient may have a reaction to the donor RBCs’ antigens, e.g.:
   1. Anaphylactic reaction (type 1 hypersensitivity reaction).
   2. Hemolytic reactions.
   3. Allergic reactions.
   4. Nonhemolytic febrile reactions.
   5. Cytopenic reactions.
   6. Tissue-immunologic reaction
2. What are the antigens that lead to reactions?
   1. Blood group ABO system.
   2. Blood group Rh system.
   3. HLA antigen (histocompatibility leukocyte antigen).
   4. Minor blood groups.
   5. Platelet antigens.
3. What are the possible Infectious organisms?
   1. Hepatitis B virus.
   2. Hepatitis C virus.
   3. HIV infection.
   4. Cytomegalovirus (CMV).
   5. Epstein-Barr virus.
   6. Malarial infection.
   7. Syphilis.
4. What are the side effects of the blood preservatives?
   1. Overload due to citrate.
   2. Depletion of coagulation factors.
   3. Hyperkalemia.
   4. Donor medications.
   5. Depletion of platelets.
   6. The temperature of the transfused blood.
5. Tissue-organ immunologic reaction:
   1. Graft-vs-host disease.

How will you treat blood transfusion reactions?

1. This is just like the type I Hypersensitivity reaction.
   1. Give epinephrine subcutaneously, 0.3 to 0.5 mL of a 1:1000 solution.
   2. Epinephrine can be repeated in 20 to 30 minutes.
2. Start O2 therapy.
3. Administer Diphenhydramine 50 mg IM; if needed, administer IV.
4. Start I/V saline to maintain blood volume and pressure.
5. If hypotension persists, administer Epinephrine IV 10 mL of 1:1000 solution.
6. For bronchospasm, administer Aminophylline 6 mg/Kg body weight initially, followed by 0.5 to 1 mg/Kg body weight.
   1. If there is severe respiratory distress, then intubate the patient. 
   2. In cases of severe laryngeal edema, a tracheostomy may be performed.
7. In a prolonged reaction, consider Hydrocortisone up to 500 mg I/V every 6 hours.

Questions and answers:

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