The Clock is Ticking
When the Immune System Misfires
Rapid Fire Next Best Step?
Lab & Imaging Detective
Not all dyspnea is the same
100

A 70-year-old man with symptomatic anemia is receiving a packed RBC transfusion. Approximately 1 hour after initiation, he develops a temperature of 38.3°C (baseline 36.8°C) with associated chills and mild malaise.

Vital signs: BP: 132/78 mmHg . HR: 92/min RR: 16/min. SpO₂: 98% on room air.

Physical examination shows no urticaria, angioedema, or wheezing. Lung auscultation is clear bilaterally. There is no jugular venous distention or peripheral edema. Urine appears clear without discoloration.

Initial labs: Hemoglobin,LDH, Haptoglobin: normal

Coombs test: negative

Which of the following is the most likely diagnosis?

A. Acute hemolytic transfusion reaction

B. Febrile nonhemolytic transfusion reaction

C. Transfusion-associated sepsis

D. Anaphylactic transfusion reaction

E. Minor allergic transfusion reaction


Answer: B. Febrile nonhemolytic transfusion reaction


100

A 19-year-old man is admitted after a motor vehicle collision with acute blood loss anemia (hemoglobin 7.4 g/dL). He has no prior history of transfusions. A packed RBC transfusion is initiated.

Approximately 2 hours into the transfusion, near completion of the unit, he develops a temperature of 38.6°C (baseline 36.8°C) associated with chills, malaise, and a mild headache.

Vital signs:

·       BP: 122/76 mmHg

·       HR: 102/min

·       RR: 18/min

·       SpO₂: 99% on room air

On physical examination, he appears uncomfortable but alert. Lung auscultation is clear bilaterally. Cardiac exam is normal, without gallop. No rash or urticaria is noted.

Urine is clear and yellow.

Initial laboratory evaluation:

·       Hemoglobin: 7.5 g/dL

·       LDH: within normal limits

·       Total bilirubin: normal

·       Haptoglobin: normal

·       Direct antiglobulin (Coombs) test: negative

Blood cultures are obtained. The patient’s symptoms improve shortly after discontinuation of the transfusion.

Which of the following best explains this reaction?

A. Preformed recipient antibodies causing intravascular hemolysis of donor RBCs

B. Donor plasma proteins binding recipient IgE on mast cells

C. Cytokines released from donor leukocytes in stored blood products

D. Antibody-mediated destruction of donor and recipient platelets

E. Bacterial contamination of the transfused product


 C. Cytokines released from donor leukocytes in stored blood products


100

A 66-year-old man develops fever ,chills and shortness of breath during a transfusion.  Which of the following is the best immediate first step?

A. Send BNP and chest imaging

B. Stop the transfusion and disconnect the tubing from the patient

C. Administer acetaminophen and continue the transfusion

D. Start broad-spectrum antibiotics

E. Give IV furosemide


Answer: B. Stop the transfusion and disconnect the tubing from the patient


100

A patient develops fever and flank pain shortly after transfusion. Which test from the following is most useful to support the suspected diagnosis of acute hemolytic transfusion reaction?

A. BNP

B. Direct antiglobulin test

C. LDH

D. Complete blood count

E. Platelet antibody testing

 

Answer: B. Direct antiglobulin (Direct Coombs) test

 


Why: DAT is the key confirmatory test in your text for AHTR.

100

A patient develops acute dyspnea during transfusion. He is hypertensive, with JVD and bibasilar crackles.

Which diagnosis is most likely?

A. TRALI

B. TACO

C. Anaphylactic transfusion reaction

D. FNHTR

E. Delayed hemolytic transfusion reaction

 


 


Answer: B. TACO

200

A 62-year-old man with anemia is receiving a packed RBC transfusion. Approximately 20 minutes after initiation, he develops fever (38.9°C), chills, and severe lower back pain.

Vital signs:

·       BP: 82/48 mmHg. HR: 122/min. RR: 22/min. SpO₂: 95% on room air

He appears anxious and diaphoretic. Lung exam is clear. No urticaria or angioedema is noted. Shortly after, his urine is noted to be dark reddish-brown.

Initial labs:

·       Hemoglobin: decreased 

·       LDH and total bilirubin: elevated 

·       Haptoglobin: decreased

Which of the following is the most likely diagnosis?

A. Acute hemolytic transfusion reaction

B. Transfusion-related acute lung injury

C. Transfusion-associated sepsis

D. Febrile nonhemolytic transfusion reaction

E. Minor allergic transfusion reaction



Acute hemolytic transfusion reaction


200

32-year-old woman is admitted for symptomatic anemia and is started on a plasma-containing blood transfusion. Within minutes of initiation, she develops acute dyspnea, chest tightness, and lightheadedness.

Vital signs:

·       BP: 78/46 mmHg

·       HR: 124/min

·       RR: 26/min

·       SpO₂: 89% on room air

 

On examination:

·       Diffuse urticarial rash over the chest and arms

·       Wheezing on lung auscultation

·       No jugular venous distention

 Her history is notable for recurrent sinopulmonary infections since childhood.

Which of the following is the most likely underlying mechanism?

A. Preformed recipient antibodies causing intravascular hemolysis of donor RBCs

B. Type I hypersensitivity reaction to donor plasma proteins in a patient with IgA deficiency

C. Cytokine-mediated inflammatory response to donor leukocytes

D. Activation of recipient neutrophils causing pulmonary capillary leak

E. Bacterial contamination of the transfused blood product


Answer: B. Type I hypersensitivity to donor plasma proteins in a recipient with IgA deficiency

 


200

A patient develops isolated urticaria and pruritus 20 minutes into a transfusion. The transfusion is stopped. He remains normotensive, without wheezing, dyspnea, fever, or chest pain.

 

Which of the following is the most appropriate next step?

A. Permanently discard the unit and do not restart transfusion

B. Administer diphenhydramine and restart slowly once symptoms resolve and anaphylaxis has been ruled out

C. Administer IM epinephrine immediately

D. Obtain blood cultures from the patient and blood product

E. Begin vasopressors


: B. Administer diphenhydramine and restart slowly once symptoms resolve and anaphylaxis has been ruled out


200

A patient develops dyspnea and hypoxemia after transfusion. Exam shows JVD and an S3 gallop. Which additional test would most strongly support TACO over TRALI? 

A. Serum LDH

B. Urinalysis for hemoglobinuria

C. BNP level

D. DAT

E. Indirect bilirubin

 



Answer: C. BNP level

200

A patient develops respiratory distress and bilateral infiltrates 2 hours after transfusion. He is febrile and hypotensive. There is no JVD or peripheral edema.

Which diagnosis is most likely?

A. TACO

B. TRALI

C. Minor allergic transfusion reaction

D. Delayed hemolytic transfusion reaction

E. Post-transfusion purpura


Answer: B. TRALI


300

A 58-year-old man is receiving a platelet transfusion for thrombocytopenia. Approximately 1 hour after initiation, he develops a temperature of 39.1°C (baseline 36.7°C), associated with severe chills and rigors.

Vital signs:

·       BP: 86/52 mmHg

·       HR: 118/min

·       RR: 24/min

·       SpO₂: 88% on room air

On exam, he appears acutely ill and diaphoretic. Lung auscultation reveals mild bilateral crackles. There is no urticaria or angioedema.

Urine is clear without visible discoloration.

Initial labs:

·       Hemoglobin: unchanged from pretransfusion level

·       LDH: within normal limits

·       Total bilirubin: normal

·       Haptoglobin: normal

Chest imaging shows no clear pulmonary edema or pleural effusions.

Which of the following is the most likely diagnosis?

A. Acute hemolytic transfusion reaction

B. Transfusion-related acute lung injury

C. Transfusion-associated sepsis

D. Febrile nonhemolytic transfusion reaction

E. Minor allergic transfusion reaction


 C. Transfusion-associated sepsis

300

A 61-year-old man with symptomatic anemia is started on a packed RBC transfusion. Within 15 minutes of initiation, he develops fever, chills, chest tightness, and severe back pain.

Vital signs:

·       Temperature: 38.8°C

·       BP: 84/50 mmHg

·       HR: 126/min

·       RR: 24/min

·       SpO₂: 96% on room air

On exam, he is diaphoretic and appears acutely ill. Lung auscultation is clear bilaterally. No urticaria or wheezing is present. Urine in the Foley bag becomes dark red-brown shortly after symptom onset.

Laboratory studies obtained later show:

·       Hemoglobin lower than expected post-transfusion

·       Elevated LDH

·       Elevated indirect bilirubin

·       Low haptoglobin

·       Hemoglobinuria

Which mechanism best explains this patient’s presentation?

A. Extravascular hemolysis from delayed alloantibody formation

B. Noncardiogenic pulmonary edema caused by neutrophil activation

C. Intravascular hemolysis due to recipient anti-A or anti-B antibodies

D. Cytokine-mediated inflammatory response to donor leukocytes

E. Antibody-mediated platelet destruction causing thrombocytopenia


 C. Intravascular hemolysis due to recipient anti-A or anti-B antibodies


 C. Intravascular hemolysis due to recipient anti-A or anti-B antibodies


300

patient develops fever during transfusion and is suspected of having FNHTR. He is stable, with no dyspnea, hypotension, hemoglobinuria, or chest pain.

Which step is still necessary before the transfusion can be safely resumed?

A. CT chest to exclude TRALI

B. Direct Coombs testing and repeat donor/patient compatibility testing to rule out AHTR

C. BNP and echocardiography to exclude TACO

D. Platelet antibody testing

E. Empiric broad-spectrum antibiotics


Answer: B. Direct Coombs testing and repeat donor/patient compatibility testing to rule out AHTR

300

A patient with suspected AHTR has the following labs:

  • elevated indirect bilirubin
  • elevated LDH
  • low haptoglobin
  • hemoglobinuria

 Which of the following best summarizes what these findings indicate?

 A. Platelet destruction with hemolysis

B. Intravascular hemolysis

C. Noncardiogenic pulmonary edema

D. Extravascular hemolysis 

E. Delayed hypersensitivity to plasma proteins

 


Answer: B. Intravascular hemolysis

300

 76-year-old man with CKD and heart failure develops hypoxemia 3 hours after transfusion. Chest imaging shows pulmonary edema. He is hypertensive. The team is debating between TRALI and TACO. 

Which feature most strongly supports TACO?

A. Onset within 6 hours

B. Bilateral pulmonary infiltrates

C. Improvement with diuretic therapy

D. Hypoxemia

E. Need for oxygen support

 


Answer: C. Improvement with diuretic therapy


400

A 72-year-old man with a history of coronary artery disease, hypertension, and stage 3 chronic kidney disease is admitted for symptomatic anemia (Hb 7.1 g/dL). He receives 2 units of packed RBCs over several hours.

Approximately 3–4 hours after completion of the transfusion, he develops acute dyspnea and tachypnea.

Vital signs:

·       Temperature: 38.1°C

·       BP: 92/58 mmHg

·       HR: 112/min

·       RR: 28/min

·       SpO₂: 85% on room air → improves to 92% on 4L nasal cannula

On physical examination:

·       Diffuse bilateral crackles are present

·       No jugular venous distention at 45°

·       No peripheral edema

·       Cardiac exam without S3 gallop

Chest radiograph shows bilateral, diffuse alveolar infiltrates without cardiomegaly or pleural effusions.

Laboratory studies:

·       BNP: 85 pg/mL (normal)

·       WBC: 13,500/mm³

·       Hemoglobin: stable compared to immediate post-transfusion value

·       LDH, bilirubin, and haptoglobin: within normal limits

 

Bedside echocardiography shows preserved left ventricular ejection fraction without evidence of elevated filling pressures.

A trial of IV furosemide is given with minimal improvement in respiratory status.

Which of the following is the most likely diagnosis?

A. Transfusion-associated circulatory overload

B. Transfusion-related acute lung injury

C. Acute hemolytic transfusion reaction

D. Transfusion-associated sepsis

E. Anaphylactic transfusion reaction


B. Transfusion-related acute lung injury

400

A 47-year-old woman is evaluated for new-onset bruising and petechiae. One week ago, she was hospitalized for gastrointestinal bleeding and received multiple units of packed RBCs. She was discharged in stable condition. She now reports progressive bruising and scattered petechiae over the past 2 days. She denies fever, dyspnea, dark urine, or hematuria.

Vital signs are stable.

Laboratory studies:

·       Platelet count: 9,000/µL (previously 220,000/µL during admission)

·       Hemoglobin: unchanged from discharge

·       LDH: normal

·       Total bilirubin: normal

·       Haptoglobin: normal

·       PT/PTT: normal

Peripheral smear shows severe thrombocytopenia without schistocytes.

Which of the following mechanisms best explains this patient’s condition?

 

A. Immune-mediated platelet destruction due to autoantibodies against platelet surface glycoproteins

B. Delayed alloantibody response against donor RBC antigens causing extravascular hemolysis

C. Antibody-mediated destruction of both donor and recipient platelets following sensitization to platelet antigens

D. Consumption of platelets due to systemic activation of coagulation pathways

E. Type I hypersensitivity reaction to donor plasma proteins


 


This is post-transfusion purpura.


400

A 56-year-old man with thrombocytopenia receives a platelet transfusion. Approximately 45 minutes after initiation, he develops fever to 39.4°C, severe chills with rigors, and increasing shortness of breath.

 

Vital signs:

·       BP: 82/50 mmHg

·       HR: 124/min

·       RR: 26/min

·       SpO₂: 90% on room air

 

On examination, he appears acutely ill and diaphoretic. Lung exam reveals mild bilateral crackles. There is no urticaria or angioedema.

 

Urine is clear without discoloration.

 

Initial labs:

·       Hemoglobin: unchanged from pretransfusion level

·       LDH: within normal limits

·       Total bilirubin: normal

·       Haptoglobin: normal

 

The transfusion is stopped, and IV access is maintained with normal saline. The blood bank is notified.

 

 

Which of the following is the most appropriate next step in management?

 

A. Acetaminophen and observation only

B. Diphenhydramine and restart transfusion slowly

C. Obtain blood cultures from the patient and remaining blood product, and start broad-spectrum empiric antibiotics

D. IM epinephrine and discharge if symptoms improve

E. Give diuretics because pulmonary edema is likely


B. Begin aggressive hemodynamic support with IV fluids and manage complications such as hyperkalemia, DIC, and renal failure


400

A patient develops acute respiratory distress within hours of transfusion. Chest imaging shows diffuse bilateral infiltrates without pleural effusions. Blood pressure is low, and there are no signs of hypervolemia.

 Which diagnosis is best supported by these findings?

 A. TACO

B. TRALI

C. Febrile Non hemolytic Transfusion Reaction

D. Delayed hemolytic transfusion reaction

E. Minor allergic transfusion reaction

 



Answer: B. TRALI

400

A patient receiving transfusion develops dyspnea, hypoxemia, and bilateral infiltrates. On exam the patient has elevated blood pressure, an S3, JVD, and peripheral edema.

Which diagnosis is  more likely? 

A. TRALI

B. TACO

C. Septic transfusion reaction

D. Acute Hemolytic Transfusion Reaction

E. Febrile non hemolytic transfusion reaction

 



Answer: B. TACO

500

A 65-year-old woman being treated with induction chemotherapy for acute myeloid leukemia develops chills and a 1.2°C increase in body temperature, without any shortness of breath or change in blood pressure, 2 hours after receiving one unit of group B, Rh-negative packed red cells. Her blood group is B, Rh-positive; she did not receive any premedication.

After she receives 650 mg of acetaminophen, her fever subsides. A clerical check confirms she received the correct unit of blood; retesting of a sample from the transfused blood showed that it had been typed correctly.

Which one of the following management approaches is most appropriate for this patient?

A. Check the serum lactate dehydrogenase level 

B. Measure the panel reactive antibody level

C. Perform a direct antiglobulin test

D. Obtain a chest radiograph

E. No further workup

C. Perform a direct antiglobulin test

500

A 78-year-old man with amyloidosis receives two units of packed red cells as treatment for severe symptomatic anemia. After 350 mL are infused, he develops shortness of breath and cough. His blood pressure increases from 120/65 mm Hg to 165/90 mm Hg, his temperature remains at 37.0°C, his heart rate increases from 65 to 104 beats per minute, and his oxygen saturation drops to 85% while he is breathing ambient air. Supplemental oxygen is provided, but the patient has an inadequate response and endotracheal intubation is required.

Physical examination reveals bulging neck veins.

A chest radiograph says bilateral patchy infiltrate.

Which one of the following approaches could have prevented this transfusion reaction?

A. Leukoreducing the blood unit

B. Administering acetaminophen before the infusion

C. Irradiating the blood units

D. Administering blood from an Rh-negative donor

E. Administering blood slowly

E. Administering blood slowly