Transfusion Complications, Emergency Medicine

Basics

Epidemiology

- Of 39 million hospital discharges in US, 5.8% (2.3 million) were associated with blood transfusions (2004). - In 2011 there were 30 deaths in US fully attributable to transfusion complications. - Some type of transfusion reaction occurs in 2% of units transfused within 24 hr of use. - Noninfectious complications: - Febrile nonhemolytic reaction: RBCs 1 in 500 transfusions, platelets 1 in 900 - Allergic reaction (nonanaphylactic): 1 in 3 to 1 in 300 - Anaphylaxis: 1 in 20,000 to 1 in 50,000 - Acute hemolytic reaction: 1 in 38,000 to 1 in 70,000 - Delayed hemolytic reaction: 1 in 4,000 to 1 in 11,000 - Transfusion-associated circulatory overload (TACO): 1 in 100, but as high as 10% in susceptible populations - Alloimmunization: 1 in 10 to 1 in 100 - Graft-versus-host disease: 1 in 400,000; rare but has >90% mortality. - Transfusion-related lung injury (TRALI): 1 in 5,000 to 1 in 190,000; represents 13% of reported transfusion-related deaths - Iron overload: Unknown incidence, depends on volume of blood, often occurs after >100 RBC units - Hypocalcemia: Unknown incidence - Hyperkalemia: Unknown incidence

- Hepatitis C: 1 in 1.6 million - Hepatitis B: 1 in 100,000 to 1 in 400,000 - HTLV I and II: 1 in 500,000 to 1 in 3 million - HIV: 1 in 1.4 million to 1 in 4.7 million - HAV: 1 in 1,000,000 - B19 parvovirus: 1 in 40,000; post-transfusion anemia rare with scattered case reports - Parasites: Babesia and malaria: <1 in 1 million - Parasites: Trypanosoma cruzi: 1 in 42,000 - Case reports of Epstein " “Barr virus, Lyme disease, brucellosis, human herpesvirus, Creutzfeldt " “Jakob disease

- 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.

- 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.

- 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

- General: - Fevers - Chills - Burning at infusion site - Urticaria/pruritus/skin erythema

- GI: - Hematologic: - Bleeding - Hemoglobinuria - Oozing from surgical wounds - Jaundice - DIC

- 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 Ž ¼g/kg/min

Of 39 million hospital discharges in US, 5.8% (2.3 million) were associated with blood transfusions (2004).
In 2011 there were 30 deaths in US fully attributable to transfusion complications.
Some type of transfusion reaction occurs in 2% of units transfused within 24 hr of use.
Noninfectious complications:Febrile nonhemolytic reaction: RBCs 1 in 500 transfusions, platelets 1 in 900Allergic reaction (nonanaphylactic): 1 in 3 to 1 in 300Anaphylaxis: 1 in 20,000 to 1 in 50,000Acute hemolytic reaction: 1 in 38,000 to 1 in 70,000Delayed hemolytic reaction: 1 in 4,000 to 1 in 11,000Transfusion-associated circulatory overload (TACO): 1 in 100, but as high as 10% in susceptible populationsAlloimmunization: 1 in 10 to 1 in 100Graft-versus-host disease: 1 in 400,000; rare but has >90% mortality.Transfusion-related lung injury (TRALI): 1 in 5,000 to 1 in 190,000; represents 13% of reported transfusion-related deathsIron overload: Unknown incidence, depends on volume of blood, often occurs after >100 RBC unitsHypocalcemia: Unknown incidenceHyperkalemia: Unknown incidence
Infectious complications:Bacterial contamination: RBCs 1 in 65,000 to 1 in 500,000; platelets 1 in 1,000 to 1 in 10,000:Most common bacterial agents: Yersinia enterocolitica, Pseudomonas spp, Serratia spp.Leading cause of mortality among infectious complications; 17 " “22% of all casesHepatitis C: 1 in 1.6 millionHepatitis B: 1 in 100,000 to 1 in 400,000HTLV I and II: 1 in 500,000 to 1 in 3 millionHIV: 1 in 1.4 million to 1 in 4.7 millionHAV: 1 in 1,000,000B19 parvovirus: 1 in 40,000; post-transfusion anemia rare with scattered case reportsParasites: Babesia and malaria: <1 in 1 millionParasites: Trypanosoma cruzi: 1 in 42,000Case reports of Epstein " “Barr virus, Lyme disease, brucellosis, human herpesvirus, Creutzfeldt " “Jakob disease

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 incompatibilityBlood type identification errorIncompatible 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-limiting1:200 U transfused
Febrile nonhemolytic transfusion reaction:Most common transfusion reaction, diagnosis of exclusion.Temperature increases at least 1 ‚ °C with chills within 6 hrAntigen " “antibody reaction to transfused blood components (WBCs, platelets, plasma)Usually mildOccurs more often with multiparous women or multiple transfusionsRecurs in 15% of patientsAcetaminophen may be used prophylactically; its use as premedication is controversial, though not harmful.
Allergic transfusion reaction:Occurs in 1% of transfusionsUsually seen with immunoglobulin A (IgA) " “deficient patientsUrticaria 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 CBlood screened for virusesBlood treated to inactivate virusesBlood donors with recent history of travel or poor health are deferred from donating.
Delayed extravascular hemolytic reaction:Occurs 7 " “10 days after transfusionAntigen " “antibody reaction that develops after transfusionCoombs test positiveUsually asymptomaticBlood bank analysis detects antibody
Electrolyte imbalance:Hypocalcemia: Calcium binds to citrateHyper/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 hostHost unable to destroy new WBCsDonor WBCs recognize host as foreign and attack hosts tissues.
Anaphylactic reaction:Can occur with <10 mL of exposureGeneralized 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 function3rd most common cause of fatal transfusionDifficult to distinguish from ARDS and TACO; often misdiagnosed and underreportedProvide supportive care.Disease is typically self-limited within 96 hr.Mortality is 5 " “10%.Diuretics contraindicated

Blood can be transfused through 22G peripheral catheter under pressure (but <300 mm Hg) with minimal hemolysis. ‚

Diagnosis

Signs and Symptoms

General:FeversChillsBurning at infusion siteUrticaria/pruritus/skin erythema
Pulmonary:DyspneaBronchospasmRespiratory distress/failure
Cardiovascular:TachycardiaHypotensionSubsternal chest pain/tightness
GI:
Hematologic:BleedingHemoglobinuriaOozing from surgical woundsJaundiceDIC
Miscellaneous:Low back painRenal 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 & Interpretation

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 productsProlonged activated PTT (aPTT)Spherocytosis
Lab findings indicating hemolysis due to Rh incompatibility:Positive Coombs testElevated indirect bilirubinPost-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 " ”patients bracelet, blood labels, call blood bank

Ed Treatment/Procedures

Hypotension:0.9% normal saline (NS) hydration with 2 large-bore IVsAvoid Ringer lactate or solutions containing dextrose.Trendelenburg positionDopamine
Prevention of renal failure:Maintain urine output of 1 mL/kg/hAdequate hydrationFurosemide or mannitol if oliguricDopamine infusion at 2 Ž ¼g/kg/min
Febrile reactions:Antipyretics (acetaminophen/nonsteroidal anti-inflammatory drugs [NSAIDs])Antihistamine (diphenhydramine + ranitidine) IVSteroids (methylprednisolone)
Allergic reactions:Antihistamine (diphenhydramine + ranitidine) IVEpinephrine for respiratory symptomsSteroids (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 Ž ¼g/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.

Additional Reading

Bakdash ‚ S, Yazer ‚ MH. What every physician should know about transfusion reactions. CMAJ. 2007;177:141 " “147.
Goodnough ‚ LT, Levy ‚ JH, Murphy ‚ MF. Concepts of blood transfusion in adults. Lancet. 2013;381:1845 " “1854.
Morton ‚ J, Anastassopoulos ‚ KP, Patel ‚ ST, et. al. Frequency and outcomes of blood products transfusion across procedures and clinical conditions warranting inpatient care: An analysis of the 2004 healthcare cost and utilization project nationwide inpatient sample database. Am J Med Qual. 2010;25:289 " “296.
Spahn ‚ DR, Goodnough ‚ LT. Alternatives to blood transfusion. Lancet. 2013;381:1855 " “1865.
Squires ‚ JE. Risks of transfusion. South Med J. 2011;104(11):762 " “769.

Codes

ICD9

780.66 Febrile nonhemolytic transfusion reaction
999.80 Transfusion reaction, unspecified
999.84 Acute hemolytic transfusion reaction, incompatibility unspecified
999.85 Delayed hemolytic transfusion reaction, incompatibility unspecified
276.61 Transfusion associated circulatory overload
279.50 Graft-versus-host disease, unspecified
518.7 Transfusion related acute lung injury (TRALI)
999.83 Hemolytic transfusion reaction, incompatibility unspecified
999.89 Other transfusion reaction

ICD10

R50.84 Febrile nonhemolytic transfusion reaction
T80.910A Acute hemolytic transfusion reaction, unspecified incompatibility, initial encounter
T80.92XA Unspecified transfusion reaction, initial encounter
T80.911A Delayed hemolytic transfusion reaction, unspecified incompatibility, initial encounter
D89.813 Graft-versus-host disease, unspecified
E87.71 Transfusion associated circulatory overload
J95.84 Transfusion-related acute lung injury (TRALI)
T80.919A Hemolytic transfusion reaction, unspecified incompatibility, unspecified as acute or delayed, initial encounter

SNOMED

82545002 Blood transfusion reaction (disorder)
435001000124103 Febrile transfusion reaction without hemolysis (disorder)
36617002 Immediate hemolytic transfusion reaction (disorder)
83250000 Delayed hemolytic transfusion reaction (disorder)
234646005 Graft-versus-host disease (disorder)
361098001 Allergic transfusion reaction (disorder)
389078002 Transfusion related acute lung injury (disorder)
79337003 Anaphylactic transfusion reaction