Acute Intravascular Hemolytic Transfusion Reaction
- Mortality and morbidity correlate with amount of incompatible blood transfused (symptoms can occur with exposure to as little as 5–20 mL)
- Occurs immediately from:
- ABO incompatibility
- Blood type identification error
- Incompatible transfused cells immediately destroyed by antibodies
- Intravascular hemolysis causing activation of coagulation system, leading to inflammation, shock, and DIC
- Mediators (cytokines) released during inflammatory response
- Renal failure:
- Cytokines cause local release of endothelin in kidney, causing vasoconstriction.
- Leads to parenchymal ischemia and acute renal failure
- Respiratory failure owing to pulmonary edema/adult ARDS:
- Free hemoglobin (Hb) causes vasoconstriction in pulmonary vasculature.
Other Transfusion-related Complications
- Hemolysis because of Rh incompatibility:
- Mild, self-limiting
- 1:200 U transfused
- Febrile nonhemolytic transfusion reaction:
- Most common transfusion reaction, diagnosis of exclusion.
- Temperature increases at least 1°C with chills within 6 hr
- Antigen–antibody reaction to transfused blood components (WBCs, platelets, plasma)
- Usually mild
- Occurs more often with multiparous women or multiple transfusions
- Recurs in 15% of patients
- Acetaminophen may be used prophylactically; its use as premedication is controversial, though not harmful.
- Allergic transfusion reaction:
- Occurs in 1% of transfusions
- Usually seen with immunoglobulin A (IgA)–deficient patients
- Urticaria alone is not a reason to stop transfusion.
- Antihistamine may be used as therapy or prophylactically.
- Premedicating with acetaminophen and diphenhydramine found to have no effect on incidence of transfusion reaction compared with placebo in some trials.
Delayed Reactions
- Infection:
- HIV, hepatitis B, hepatitis C
- Blood screened for viruses
- Blood treated to inactivate viruses
- Blood donors with recent history of travel or poor health are deferred from donating.
- Delayed extravascular hemolytic reaction:
- Occurs 7–10 days after transfusion
- Antigen–antibody reaction that develops after transfusion
- Coombs test positive
- Usually asymptomatic
- Blood bank analysis detects antibody
- Electrolyte imbalance:
- Hypocalcemia: Calcium binds to citrate
- Hyper/hypokalemia: Citrate metabolized to bicarbonate, which drives potassium intracellularly; prolonged storage of blood may cause hemolysis and hyperkalemia
- Graft-versus-host disease:
- Fatal in >90%
- Immunologically competent lymphocytes transfused into immunocompetent host
- Host unable to destroy new WBCs
- Donor WBCs recognize host as foreign and attack host’s tissues.
- Anaphylactic reaction:
- Can occur with <10 mL of exposure
- Generalized flushing, urticaria, laryngeal edema, bronchospasm, profound hypotension, shock, or cardiac arrest.
- Treat with subcutaneous epinephrine, supportive hemodynamic and respiratory care.
- TRALI:
- Symptoms typically begin with 6 hr of transfusion.
- Acute onset of respiratory distress, bilateral pulmonary edema, fever, tachycardia, hypotension, with normal cardiac function
- 3rd most common cause of fatal transfusion
- Difficult to distinguish from ARDS and TACO; often misdiagnosed and underreported
- Provide supportive care.
- Disease is typically self-limited within 96 hr.
- Mortality is 5–10%.
- Diuretics contraindicated
Pediatric Considerations
Blood can be transfused through 22G peripheral catheter under pressure (but <300 mm Hg) with minimal hemolysis.
DIAGNOSIS
SIGNS AND SYMPTOMS
- General:
- Fevers
- Chills
- Burning at infusion site
- Urticaria/pruritus/skin erythema
- Pulmonary:
- Dyspnea
- Bronchospasm
- Respiratory distress/failure
- Cardiovascular:
- Tachycardia
- Hypotension
- Substernal chest pain/tightness
- GI:
- Hematologic:
- Bleeding
- Hemoglobinuria
- Oozing from surgical wounds
- Jaundice
- DIC
- Miscellaneous:
- Low back pain
- Renal failure (oliguria/anuria)
- Classic triad of fever, flank pain, and red-brown urine of acute hemolytic reactions is rarely seen.
ESSENTIAL WORKUP
- Recognize clinical findings of transfusion reaction.
- Recheck identifying information of blood and patient compatibility.
- Recognize evidence of hypotension/shock, severe respiratory distress, sepsis, fever, and urticaria; intervene appropriately.
DIAGNOSIS TESTS & NTERPRETATION
Lab
- CBC
- Electrolytes, BUN, creatinine, glucose:
- For electrolyte abnormalities
- PT, PTT
- Serum calcium
- Fibrinogen, fibrin degradation products
- Bilirubin (direct/indirect)
- Coombs test
- Hemoglobinemia:
- Pink or red supernatant of plasma or serum indicates hemolysis.
- Urinalysis:
- Hemoglobinuria: Dipstick-positive blood without RBCs on micro
- Lab findings indicating hemolysis:
- Thrombocytopenia (<100,000)
- Fibrinogenopenia (<150 mg/L)
- Fibrin degradation products
- Prolonged activated PTT (aPTT)
- Spherocytosis
- Lab findings indicating hemolysis due to Rh incompatibility:
- Positive Coombs test
- Elevated indirect bilirubin
- Post-transfusion Hb/hematocrit not showing expected rise
Imaging
Chest radiograph: Diffuse patchy infiltrates without cardiomegaly if TRALI.
Diagnostic Procedures/Surgery
ECG for dysrhythmia, sign of electrolyte abnormality
DIFFERENTIAL DIAGNOSIS
- Sepsis
- Anaphylaxis/allergic reaction to medication
TREATMENT
PRE HOSPITAL
Routine stabilization
INITIAL STABILIZATION/THERAPY
- Immediately stop infusion:
- Severity of reaction proportional to amount of blood transfused
- ABCs
- Supplemental oxygen—intubation and mechanical ventilation if needed
- Recheck blood-identifying information—patient’s bracelet, blood labels, call blood bank
ED TREATMENT/PROCEDURES
- Hypotension:
- 0.9% normal saline (NS) hydration with 2 large-bore IVs
- Avoid Ringer lactate or solutions containing dextrose.
- Trendelenburg position
- Dopamine
- Prevention of renal failure:
- Maintain urine output of 1 mL/kg/h
- Adequate hydration
- Furosemide or mannitol if oliguric
- Dopamine infusion at 2 μg/kg/min
- Febrile reactions:
- Antipyretics (acetaminophen/nonsteroidal anti-inflammatory drugs [NSAIDs])
- Antihistamine (diphenhydramine + ranitidine) IV
- Steroids (methylprednisolone)
- Allergic reactions:
- Antihistamine (diphenhydramine + ranitidine) IV
- Epinephrine for respiratory symptoms
- Steroids (methylprednisolone)
- Redraw blood sample for repeat ABO/Rh typing, direct antiglobulin testing.
- Foley catheter to monitor urine output
- Replenish calcium if hypocalcemia develops.
- Treat DIC
MEDICATION
- Calcium gluconate: 10 mL of 10% (peds: 100 mg/kg/dose) solution slow IV push
- Dopamine: 2–20 μg/kg/min IV
- Diphenhydramine: 25–50 mg (peds: 1.25 mg/kg) IV or PO
- Ranitidine: 50 mg IV (peds: 1–2 mg/kg/dose max. 50 mg)
- Epinephrine (1 in 1,000): 0.3–0.5 mL (peds: 0.01 mL/kg) SC
- Methylprednisolone: 125 mg (peds: 2 mg/kg) IV
FOLLOW-UP
DISPOSITION
Admission Criteria
- Acute hemolytic transfusion reaction, pulmonary complications, anaphylaxis, sepsis:
- Delayed hemolytic transfusion reactions for evaluation/treatment
- Electrolyte abnormalities requiring cardiac monitoring
Discharge Criteria
Uncomplicated febrile or allergic reaction
PEARLS AND PITFALLS
- Blood transfusion is substantially over utilized and has significant associated risk, such as transfusion reactions, transmission of pathogens, and immune suppression.
- Maintaining body temperature during massive transfusion is crucial to correcting coagulopathy.
- Failure to properly compare patient identification to labeling on blood or failure to wait for fully cross-matched blood carries significant risks.
- Suspect acute intravascular hemolysis if patient develops hypotension, dark urine, or oozing from IV or other puncture sites.