Blood Transfusion Reactions

Seconds-minutes

Anaphylaxis
- IgE-mediated hypersensitivity
- Rash, angioedema, wheezing, hypotension
- Management: Intramuscular epinephrine injection + steroids

Minutes-hours

Acute Hemolytic Reaction
- Recipient antibodies to donor RBC antigens (usually ABO antigens), as a result of improper cross-matching prior to administration
- Fever, chills, flank pain, hemoglobinuria, potentially progressing to renal failure and DIC
- High unconjugated bilirubin, high LDH, low haptoglobin, Coombs-positive
- Management: STOP transfusion, give normal saline (not LR, LR has calcium which can coagulate any blood remaining in the IV), at recommended rate 1 ml/kg/hr to prevent hypotension and renal injury . Can supplement with blood products as needed if patient is in DIC. _(1-2)

~1-6 hours

Febrile Non-Hemolytic Reaction
- When donor blood is in storage, residual WBCs release cytokines. These cytokines cause a fever when introduced to the patient
- Fever with normal LDH, haptoglobin, and bilirubin
- Management: STOP transfusion, give antipyretics. Use leukoreduced blood products in the future

TACO (Transfusion-Associated Circulatory Overload)
- Volume overload in the setting of blood product administration
- Dyspnea, bilateral pulmonary infiltrates seen on CXR (similar to TRALI)
- No fever, +JVD, hypertensive, elevated BNP, good response to diuretics
- Management: Diuresis

TRALI (Transfusion-Associated Lung Injury)
- Two-hit hypothesis ₍₃₎
  - 1st: Sequestration/priming of neutrophils and endothlium from an inflammatory state (such as sepsis, malignancy, etc.) in the pulmonary endothelium prior to transfusion
  - 2nd: Various substances in the transfused blood activate the neutrophils and endothelium, causing inflammation and fluid leakage in the pulmonary vasculature
- Dyspnea, bilateral pulmonary infiltrates seen on CXR (similar to TACO)
- +Fever, no JVD, hypotensive, normal BNP, unreliable response to diuretics
- Management: Treat as ARDS (see ARDS) with essentially supportive treatment and lung-protective ventilation

Days-Weeks

Delayed Hemolytic Reaction
- Immune system reaction to RBC antigen that it is has previously been exposed to (e.g. pregnancy, prior reaction), usually minor antigens (i.e. Rh) ₍₄₎
- May be asymptomatic or have symptoms of anemia (fatigue, lightheadedness, etc.) or have signs of jaundice and “tea-colored” urine (hemoglobinuria)
- High unconjugated bilirubin, high LDH, low haptoglobin, Coombs-positive
- Management: Supportive: close monitoring of hemoglobin levels and renal function. +/- antipyretics if febrile ₍₅₎

What to Do When Issues are Encountered with Blood Transfusion

Stop blood transfusion
Get IM epinephrine ready and consider having IV methylprednisolone or diphenhydramine ready
Look for wheezing, angioedema, rash (if present, likely anaphylaxis and epinephrine would be indicated)
Assess oxygenation saturation (consider CXR if inadequate oxygen saturation to eval for TACO vs TRALI)
If none of the above are present, start normal saline 1 mg/kg/hr for an acute hemolytic reaction and give antipyretics as needed and continue to monitor
Check labs (CBC with dif, CMP, LDH, haptoglobin) in the meantime to differentiate acute hemolytic reaction from febrile nonhemolytic reaction
Close monitoring of hemoglobin levels

References

Singh, S. (2020, December 05). Ringer’s lactate. Retrieved February 05, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK500033/
Harewood, J. (2020, August 16). Hemolytic transfusion reaction. Retrieved February 05, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK448158/#_article-22740_s7_
Kim, J., & Na, S. (2015, April). Transfusion-related acute lung injury; clinical perspectives. Retrieved February 05, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4384395/
Zerra, P., & Josephson, C. (2018, September 14). Delayed hemolytic transfusion reactions. Retrieved February 05, 2021, from https://www.sciencedirect.com/science/article/pii/B9780128137260000647
Strobel, E. (2008). Hemolytic transfusion reactions. Retrieved February 05, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3076326/