blood transfusion and transfusion reactions

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BLOOD TRANSFUSION AND TRANSFUSION REACTIONS Banadir Hospital-somalia Pediatric department Emergency ward –CME lectures Mohamed Adan Aweys (Marwan) [email protected]

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Page 1: Blood transfusion and transfusion reactions

BLOOD TRANSFUSION AND TRANSFUSION REACTIONS

Banadir Hospital-somalia Pediatric department

Emergency ward –CME lectures Mohamed Adan Aweys (Marwan)

[email protected]

Page 3: Blood transfusion and transfusion reactions

LEARNING OUTCOMES

At the end of this topic, you should able to:

• Understand concept of Whole blood and blood components

• Discuss types and indications of blood transfusion

• Enlist tests to be performed prior to blood transfusion

• Understand transfusion reactions and their managements.

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Blood Transfusion • Process of transferring blood-based products from one person into

the circulatory system of another through an intravenous line.• The appropriate use of blood means the transfusion of safe blood

products only to treat a condition leading to significant morbidity or mortality that cannot be prevented or managed effectively by other means.• Transfusion carries the risk of adverse reactions and transfusion-

transmitted infection. Plasma can transmit most of the infections present in whole blood and there are very few indications for its

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TRANSFUSION THERAPY * REPLACEMENT * THERAPEUTIC1.To restore intravascular volume with whole blood or albumin.2. To restore the oxygen capacity of blood by replacing red blood cells.3. To replace clotting factor and correction of anemia

PURPOSE OFBLOOD

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Blood safety transfusion-transmissible infection window period : is the period during the development of a new

infection in a previously non-infected person in which the person’s blood may be very infectious, but the detectable antibody has not yet appeared.

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WHOLE BLOOD AND BLOOD COMPONENTS• 350ml /450 ml of blood is collected from a donor into a

plastic bag containing an anticoagulant

• This is called 1 “unit” of whole blood

• Types of blood components:-• Red blood cell concentrate (packed red blood cells)• Platelet concentrate• Fresh frozen plasma Cryoprecipitate

Plasma or platelets collected by apheresis.Apheresis: a method of collecting plasma or platelets directly from

the donor, usually by a mechanical method

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Dr. Salwa Hindawi

Whole blood

Plateletsrich

plasma

1stcentrifugation

Platelets concentrate

Whole bloodWhole blood

2nd centrifugation

Fresh plasma

FFP for clinical use

FFP for fractionation

Optimal additive solution

Red cells in OAS

Cryoprecipitate

RedCell

concentrate

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Effects of storage on whole blood

■ Reduction in the pH (blood becomes more acidic) ■ Rise in plasma potassium concentration (extracellular K+) ■ Progressive reduction in the red cell content of 2,3 diphosphoglycerate

(2,3 DPG) which may reduce the release of oxygen at tissue level until 2,3 DPG is restored ■ Loss of all platelet function in whole blood within 48 hours of donation ■ Reduction in Factor VIII to 10–20% of normal within 48 hours of

donation. Coagulation factors such as VII and IX are relatively stable in storage

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TYPES OF BLOOD TRANSFUSION

• FRESH BLOOD TRANSFUSION Blood less than 24 hours old from the time of collection • AUTOLOGOUS TRANSFUSION Blood collected from a patient for re-transfusion at a later time

into the same individual

• MASSIVE TRANSFUSION Number of units transfused in a 24 hours period exceeds the

recipient’s blood volume

• MULTIPLE TRANSFUSION Repeated transfusion of blood over a long period of time

(months or year)

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INDICATIONS OF BLOOD TRANSFUSION• Whole Blood:Storage -4° for up to 35 days• Acute blood loss (trauma ) • Shock• Exchange transfusion in neonate

• Considerations• Use filter as platelets and coagulation factors will not be active

after 3-5 days• Packed red blood cells: Storage - 2 – 6 O C• Chronic severe Anemia• Leukemia• Thalassemia

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• Platelets concentrate: Platelet viability is optimal at 22° C but storage is limited

to 4-5 days .1 unit/10 kg of body weight increases Plt count by 50,000• Thrombocytopenia <15,000• Bleeding due to platelet dysfunction • Malignancy• Major surgery

• Fresh frozen plasma: Storage FFP-12 months at –18 degrees or colder• Liver disorders• DIC• Coagulation factor deficiency (V, VII)

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Cryoprecipitate:Description

Precipitate formed/collected when FFP is thawed at 4°StorageAfter collection, refrozen and stored up to 1 year at -18

• Hemophilia A (Factor VIII or XIII deficiency ) • von Willebrand’s disease• Fibrinogen deficiency

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PRE-TRANSFUSION TESTING

• ABO and Rh (D) blood grouping :• Patient’s and donor’s blood sample

• Cross matching of blood sample:• Major cross match- Pt’s serum + Donor cells• Minor cross match- pt’s cells + Donor serum

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BLOOD GROUPING

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PRE-TRANSFUSION TESTING (contd.)

• Screening for Transfusion transmitted diseases (Donor Sample) HIV 1 and 2 AIDS HBsAg Hepatitis B HCV Hepatitis C Treponema pallidum Syphilis Plasmodium species Malaria

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Transfusion Reactions• Infectious

• Viral• Bacterial

• Noninfectious• Reaction to RBC Antigens

• Acute Hemolytic Transfusion Reactions (AHTR)• Delayed Hemolytic Transfusion Reactions (DHTR)

• Reactions to Donor Proteins• Minor Allergic Reactions• Anaphylactic Reactions

• White Cell-Related Transfusion Reactions• Febrile Reactions• Transfusion-Related Acute Lung Injury (TRALI)

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CAUSES OF TRANSFUSION REACTIONS

• Clerical errors:• Inadequate labeling• Wrong blood issued

• Technical errors:• Error in blood grouping & cross matching• Incorrect interpretation of test results

• Others:• Blood contamination during phlebotomy• Blood infusion thr’ small bore needle• Blood cooler to -30⁰C or warmed to > 42⁰ C • Concomitant administration blood & drugs thr’ common set

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How to Prevent Errors in the Transfusion Chain

Where in the process do errors occur?

Who is making the errors?

Why are the errors occuring – which elements of good transfusion practice are failing

Sample ErrorSample Error Technical ErrorTechnical Error

Wrong BloodWrong Blood IssuedIssued Storage ErrorStorage Error

Patient Patient MisidentificationMisidentification

Administrative Administrative ErrorError

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CLASSIFICATION Transfusion reaction

acute delayed

Immunologic Non immunologic Immunologic Nonimmunologic

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Acute Transfusion Reactions• Hemolytic Reactions (AHTR)• Febrile Reactions (FNHTR)• Allergic Reactions• TRALI(Transfusion related acute lung injury)• Coagulopathy with Massive transfusions• Bacteremia

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Febrile (non haemolytic) Transfusion Reaction (FNHTR)

Rise in patient temperature >1°C (associated with transfusion without other fever precipitating factors

Onset during or within 4 hours following transfusion , Reaction induced by cytokines.

Occurs with approx 1% of PRBC transfusions and approx 20% of Plt transfusions

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• Mild: unexplained fever ≥38°C and a temperature rise of at least 1°C but <1.5°C from pre-transfusion baseline, occurring in the absence of chills, rigors, respiratory distress and haemodynamic instability • Moderate: unexplained fever ≥38°C and a temperature rise of at

least 1°C but not meeting criteria for either mild or severe FNHTR • Severe: unexplained fever >39°C and a temperature rise ≥2.0°C from

pre-transfusion baseline and chills/rigors . • STOP TRANSFUSION• Check label and recipient identity • Slow the transfusion if reaction is mild and MO elects to continue

transfusion • Antipyretic Paracetamol 1g po and monitor closely • Steroids are not appropriate treatment for minor reactions ••

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Acute Hemolytic Transfusion Reactions (AHTR)• Occurs when incompatible RBC’s are transfused into a recipient who has pre-

formed antibodies (usually ABO or Rh)• Antibodies activate the complement system, causing intravascular hemolysis• Symptoms occur within minutes of starting the transfusion• This hemolytic reaction can occur with as little as 1-2 cc of RBC’s• Labeling error is most common problem• Can be fatal

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Signs and Symptoms• Fever , Chills, rigors • Nausea and vomiting• Hypotension and tachycardia (bradykinin)• Flushed and dyspneic (histamine)• Chest, abdominal or low back pain (cytokine release)• Headache• Haemoglobinaemia and haemoglobinuria • Oliguria with dark urine or anuria• Pallor, jaundice - Bleeding (due to DIC)

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• Stop transfusion • Check label and recipient identify • Replace IV set and start normal saline • Treat shock and maintain blood pressure with IV saline

infusion • Investigate possible DIC and treat if clinically significant

bleeding • Diuretic, eg Frusemide 1-2 mg/kg IV and/or Mannitol, may

help maintain urine flow • Hydrocortisone may be considered • Samples to assess renal and liver function, DIC and

haemolysis, eg full blood count, unconjugated bilirubin, LDH and haptoglobin • Send Haemovigilance notification to Blood Bank

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Delayed Hemolytic Transfusion Reactions

• Onset usually 1-7 days post transfusion but may be up to 28 days.• Worsening anaemia and jaundice from destruction of red cells

Often asymptomatic but rarely splenomegaly, haemoglobinaemia and haemoglobinuria .• Renal impairment may occur in severe cases Investigate haemolysis: Full blood count with film comment

Direct antiglobulin test (may be negative when most red cells cleared)

Blood group antibody screen (may be negative until red cells cleared) Liver function tests Haptoglobin concentration falls while haemolysis is occurring

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Allergic Transfusion ReactionsAllergic Reaction (minor) Frequency: 1:100 - 1:500 More common with Plasma and Platelet Components . Onset: from commencement to 4 hours after transfusion Recipient may have an antibody

reacting with an antigen in the transfused product .Minor or localised reaction: Flushed skin Morbilliform rash with itching Urticaria (hives) Angioedema Periorbital itch, erythema and oedema Conjunctival oedema Minor oedema of lips, tongue and uvula

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Management Slow transfusion Check label and recipient identity Antihistamine, eg Loratadine 10mg or Cetirizine

10mg po if symptoms are troublesome If symptoms mild and transient, transfusion may

resume Continue transfusion at a slower rate with increased

monitoring, eg BP/TPR 15 – 30minSend Haemovigilance notification to Blood Bank If symptoms increase treat as a moderate or severe

reaction

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Allergic Reaction (moderate) Frequency: 1:500–1:5,000 Onset usually within first 50-100 mL infused and within

4 hours of transfusion .Moderate or widespread reaction: Symptoms as for minor reactions, and – Cough Hypotension and tachycardia Dyspnoea and oxygen desaturation are common Chills and rigors Loin pain and angina Severe anxiety

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Management • Stop transfusion• Check label and recipient identity • Replace IV set and give saline to keep vein open and/or

maintain BP • Monitor closely and treat symptomatically as required

with IV fluids, oxygen and antihistamine, eg Promethazine 25-50 mg IV (max rate 25 mg/min) or Loratadine 10mg or Cetirizine 10mg po. Hydrocortisone may be considered • Send Haemovigilance notification to Blood Bank• Discuss with TMS promptly if mod - severe reaction

present

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Anaphylactic / Anaphylactoid Allergic Reaction (severe) Frequency: 1:20,000 – 1:50,000 Rapid onset : - May be due to an antibody in the recipient reacting with a plasma protein in a blood component - IgA - Haptoglobin o Other plasma protein.Life-threatening reaction: Symptoms as for moderate reactions, and Severe hypotension, shock and tachycardia Widespread urticaria with skin flushing and itching Wheezing, stridor, change in voice Severe anxiety

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Management Stop transfusion Check label and recipient identity Follow Anaphylaxis Guidelines: • Adrenalin 1:1000 IM and repeat at 5- 10 min intervals if required: - Adult:

0.5mg / 0.5 mL - Children 0.01mg/kg IM; min dose 0.1mL, max dose 0.5mL• Replace IV set and give rapid IV colloid or saline, eg adults 2 L, children 20

mL/kg, until SBP>90 mmHg, then titrate • Consider Hydrocortisone 4mg/kg (200- 400 mg IV) • Consider H1-antihistamine, eg Loratadine or Cetirizine 10 mg po for itch or

angioedema. • H2-antihistamine, eg Ranitidine may be added for severe reactions. • Note: Sedating antihistamines, eg Promethazine contraindicated CPAP ventilation, chest X-ray ICU liaison Discuss severe reactions with TMS

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TRALI: Transfusion Associated Lung Injury

• Frequency: <1:5,000 • Onset within 6 hours following transfusion of plasma or plasma-

containing cellular components • A complex group of disorders indistinguishable clinically from ARDS • One recognised mechanism involves a donor antibody reacting with

recipient neutrophil- or HLA-antigens causing cell activation that results in acute severe microvascular lung injury .

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• Onset of severe dyspnoea and cyanosis proceeding to respiratory failure with bilateral infiltrates on CXR within 6 hours of transfusion .• Absence of left atrial hypertension (circulatory overload)Distinguish from: cardiovascular overload (TACO) oother causes of acute respiratory distress syndrome (ARDS) or less severe acute lung injury (ALI)Management - Intensive care management for respiratory failure - Diuretics are not usually helpful

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TACO: Transfusion Associated Circulatory Overload• Rapid onset after infusion of a volume of fluid that is clinically

significant for the affected recipient. • Main risk factors: premature/ new borne or Elderly patients

recipient with impaired cardiovascular state or renal impairment o Infusion too rapid for recipient o Volume infused too great, especially if normovolaemic.• Clinics: Acute heart failureProphylaxis: Slow infusion rate, low volume of transfusion

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Increased blood pressure Rapid bounding pulse Respiratory distress with raised resp. rate, dyspnoea, cough, pink

frothy sputum, crepitations and oxygen desaturation consistent with pulmonary oedema

Raised JVP and CVP Nausea Acute or worsening pulmonary oedema on CXR Restlessness, anxiety Management Stop transfusion Seek urgent medical assessment Sit recipient upright with legs over side of bed, administer oxygen,

diuretic (Frusemide 1-2 mg/kg IV), CPAP ventilation. Demonstration of raised BNP may help to distinguish from TRALI

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TRALI versus TACO

Kim et al. 2015.

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Bacterial Contamination(Bacterial Sepsis)• More common and more severe with platelet transfusion (platelets are stored at room

temperature)• Organisms

• Platelets—Gram (+) organisms, ie Staph/Strep• RBC’s—Yersinia, enterobacter

Symptoms : - Rigor, chills, fever -Shock, usually within minutes of starting transfusion -Respiratory distress, wheezing and oxygen desaturation-Pain up arm , Chest and back / loin pain Nausea, Give antibiotics: a broad-spectrum penicillin or cephalosporin and gentamicin 5mg/kg.

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Cooling Progressive onset during rapid infusion of large

volumes of cold fluids, including blood products (more than 50 mL/kg/h in adults or 15 mL/kg/h in children.

Signs And Symptoms • Reduced temperature • May be associated with cardiac rhythm irregularity and

a negative inotropic effect• Impaired platelet function and coagulationLimit heat loss from the recipient and monitor BP/TPR If further blood components required, infuse through a

warmer

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Chronic Transfusion ReactionsoAlloimmunizationoTransfusion Associated Graft Verses Host Disease (GVHD)o Iron OverloadoTransfusion Transmitted InfectionoPost Transfusion Purpura : (Onset about 5-12 days after transfusion of cellular blood components ,• Severe thrombocytopenia often with purpura and possibly other

bleeding .• Thrombocytopenia will persist for 1-2 weeks

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Transfusion Related Graft- versus -Host Disease

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General managements of Acute transfusion reactions

• category 1: Mild reactions• Urticaria and itching are not uncommon reactions following transfusion. They arise as a result of hypersensitivity

with local histamine release to proteins, probably in the donor plasma.

• Signs and symptoms• Localised cutaneous reactions (urticaria and rash), often accompanied by pruritus (intense itching), occur within

minutes of commencing the transfusion. The symptoms usually subside if the transfusion is slowed and antihistamine is given.

Management

1- Slow the transfusion.

2 -Give an antihistamine: e.g. chlorpheniramine 0.1 mg/kg by intramuscular injection.

3- Continue the transfusion at the normal rate if there is no progression of symptoms after 30 minutes.

4- If there is no clinical improvement within 30 minutes or if signs and symptoms worsen, treat the reaction as a Category 2 reaction.

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Category 2: Moderately severe reactionsSigns and symptoms usually occur 30–60 minutes after the start of the transfusion.Signs

■ Flushing Urticaria■ ■ Rigor Fever■ ■ Restlessness Tachycardia■

Symptoms ■ Anxiety Pruritus (itching)■ ■ Palpitation Mild dyspnoea■ ■ Headache

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1- Stop the transfusion. Replace the infusion set and keep the IV line open with normal saline.

3- Administer antihistamine IV or IM (e.g. chlorpheniramine 0.01 mg/kg or equivalent) and an oral or rectal antipyretic (e.g. paracetamol 10 mg/kg: 500 mg – 1 g in adults). Avoid aspirin in thrombocytopenic patients.

4- Give IV corticosteroids and bronchodilators if there are anaphylactoid features (e.g. broncospasm, stridor).

5- Collect urine for the next 24 hours for evidence of haemolysis and send to the laboratory.

6- If there is a clinical improvement, restart the transfusion slowly with a new unit of blood and observe carefully.

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Category 3: Life-threatening reactionsThe most common causes of life-threatening transfusion reactions are:

■ Acute intravascular haemolysis ■ Bacterial contamination and septic shock ■ Fluid overload ■ Anaphylactic shock ■ Transfusion-associated lung injury (TRALI)

Signs• Rigors• Fever• Restlessness• Shock• Tachycardia• Haemoglobinuria (red urine)• Unexplained bleeding (DIC)

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Symptoms ■ Anxiety ■ Chest pain ■ Respiratory distress/shortness of breath ■ Loin/back pain ■ Headache ■ Dyspnoea

Management1- Stop the transfusion and Check label and recipient identity - Replace the infusion set and keep IV line open with normal saline.2- Infuse normal saline to maintain systolic BP (initial 20–30 ml/kg).

If hypotensive, give over 5 minutes and elevate patient’s legs.3- Maintain airway and give high flow oxygen by mask.

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4 -Give 1:1000 adrenaline 0.01 mg/kg body weight by intramuscular injection.- Children 0.01mg/kg IM; min dose 0.1mL, max dose 0.5mL

5- Give IV corticosteroids ( Consider iv Hydrocortisone 4mg/kg (200- 400 mg ) and bronchodilators if there are anaphylactoid features (e.g. broncospasm, stridor).

6 -Give diuretic: e.g. frusemide 1 mg/kg IV or equivalent

7- Consider H1-antihistamine, eg Loratadine or Cetirizine 10 mg po for itch or angioedema.

o H2-antihistamine, eg Ranitidine may be added for severe reactions.

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Reference • American Society of Hematology 2021 L Street NW, Suite 900

Washington, DC 20036• www.hematology.org• 2012 Clinical Practice Guide on Red Blood Cell Transfusion • Handbook of Transfusion Medicine. Fourth Edition.

www.transfusionguidelines.org.uk

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ThAnk You!Hope you learned

something!

Page 55: Blood transfusion and transfusion reactions

Case 1Mr gulled is a 14 year old male is brought to

the ER after a motor vehicle accident. He is in pain, tachycardic to 120s, but normotensive. • Given his acute blood loss, transfusion of 1u

PRBC is initiated (after appropriate type and cross-matching revealing no antibodies, and compatibility with donor blood). • During transfusion, he develops a fever but

otherwise has no new signs or symptoms. • What is the diagnosis?

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Febrile Nonhemolytic Transfusion Reaction

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Case 1 (continued)• Mr gulled does well following discharge. Fifteen years

later (age 29 ), however, he is unfortunately in a second MVA. He is brought to the ER, again requiring blood products. • He is type and cross-matched, found to have no

antibodies. He is pre-treated with acetaminophen, and transfused 2 units PRBC without issue. • The remainder of his hospital course is unremarkable

and the pt is discharged home.• Ten days after the accident he follows up at his PCP’s

office with a complaint of fatigue, fevers, and yellowing of his skin.• What is the diagnosis?

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Delayed Hemolytic Transfusion Reaction

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Case 1 (continued)• Mr gulled is now 78 years old. Since we

last saw him, he has been diagnosed with diabetes, complicated by ESRD 2/2 diabetic nephropathy for which he is dialyzed three times per week.

• He is admitted for a suspected GI bleed for which he is transfused 2 units PRBC. An hour after transfusion, he starts to complain of shortness of breath and chest tightness. HR 120s, BP 180/90, an S3 gallop is noted, and new bibasilar crackles are heard on pulmonary exam. Post-transfusion CXR is shown (was previously normal).

• What is the diagnosis?https://www.med-ed.virginia.edu/courses/

rad/cxr/pathology2chest.html

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CXR w/ Sudden SOB.

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What is The Most Likely DiagnosisA) Pulmonary EmbolismB) Transfusion Related Acute Lung InjuryC) Transfusion Associated Circulatory OverloadD) AnaphylaxisE) Acute Respiratory Distress Syndrome

More common than TRALI (1 in 100 vs 1 in 10,000). This case was confirmed to be TACO.

PE usually causes respiratory alkalosis with hypoxia on ABG. Anaphylaxis should be considered but TACO is more likely in this scenario. ARDS is less likely given no evidence of infection or inflammation prior to the

sudden event.

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Transfusion-Associated Circulatory Overload (TACO)

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Case 3. Back to Mr gulled…• Mr gulled is now 80 years old and is admitted after a fall during which

he sustained a left hip fracture. Following surgery, he requires 1 unit PRBC. He is appropriately type and crossmatched, pretreated with acetaminophen, and a slow transfusion is initiated during dialysis. During the transfusion, he develops diffuse urticaria but is otherwise stable. • What is the diagnosis?

umm.edu

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Allergic Reactions and Anaphylaxis