Transfusion Reactions NICHOLAS TSU, M.D.

Objectives Transfusion statistics and basics Types Diagnosis Treatment

Transfusion Statistics Transfusions in 2004 14.2 million units of packed red blood cells (PRBC’s) 9.9 million units of platelets (84% apheresis units) 4.1 million units of fresh-frozen plasma (FFP) Approximately 40% of all transfused units administered by anesthesia personnel

Transfusion Risks Infectious Noninfectious Viral Bacterial 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)

Viral Infections

Bacterial Infections

Bacterial Infections Incidence of sepsis much greater in platelets Platelets stored at room temperature Decreased risk with apheresis platelets Most common organisms Staphyloccos aureus Klebsiella pneumoniae Serratia marcescens Staphyloccos epidermdidis Yersinia enterocolitica

Bacterial Sources Donor skin flora Donor bacteremia Contamination from Collection Processing Storage

Signs and Symptoms of Bacterial Infection Fevers Chills Tacycardia Dyspnea Emesis Shock DIC Acute renal failure

Diagnosis and Treatment Stop transfusion Obtain blood cultures Treat with broad spectrum antibiotics Notify the blood bank immediately Prevent other units from same donor being transfused

Acute Hemolytic Transfusion Reactions Most hazardous against foreign RBC’s Hemolysis of donor RBC’s can lead to ARF & DIC Mortality rate is 2% Leading cause is clerical error

Acute Hemolytic Transfusion Reactions Over 300 antigens on human RBC’s Most common antibodies that fix complement A, B, Kell, Kidd, Duffy Rh antibodies do not fix complement but can cause serious hemolysis

AHTR Pathophysiology Antibodies and complement in recipient plasma attack antigens on donor RBC’s causing hemolysis Antigen-antibody complexes activate Hageman factor (factor XII) producing bradykinin leading to capillary permeability and hypotension Complement system releases histamine and serotonin from mast cells resulting in bronchospasm 30-50% of patients will develop DIC

AHTR Pathophysiology Hemolysis releases hemoglobin (Hb) Hb binds to haptoglobin and albumin initially Will circulate unbound until excreted by kidneys Renal damage causes Hypotension 2/2 systemic hypotension and renal vasoconstriction Free Hb form acid hematin damaging renal tubules Antigen-antibody complexes may deposit in glomeruli

Signs and Symptoms Fever Chills Nausea and vomiting Diarrhea Rigors Hypotension and tachycardia (bradykinin) Flushed and dyspneic (histamine) Chest and back pain (cytokine release) Headache Feeling of impending doom Hemoglobinuria eventually oliguria

Diagnosis Stop transfusion Recheck patient and unit labeling Examine centrifuged plasma sample for pinkish discoloration representing free Hb Hemolysis should be assumed to be hemolytic transfusion reaction until proven otherwise Notify blood bank Aseptically seal unit and return Coombs test Examines recipient RBC’s for presence of surface immunoglobulins and complement

Treatment Maintain systemic blood pressure Deliver volume Pressors Inotropes Preserve Renal function and urine output Administering fluids Diuretics (mannitol or furosemide) Sodium bicarb to alkalinize urine Prevent DIC No specific therapy Prevent hypotension and support cardiac output Decreases stasis

Delayed Hemolytic Transfusion Reactions Compatible RBC’s are rapidly eliminated within days Typically due to donor RBC antigen to which recipient has been previously exposed via transfusion or pregnancy Over time antibody levels fall too low to be detected With re-exposure anamnestic response results in antibodies and lysis of foreign RBC’s Coated RBC’s are sequestered extravascularly (spleen and reticuloendothelial system) and lysed

Diagnosis and Treatment Usually detected in the first or second week Low-grade fever Increased indirect bilirubin Unexplained reduction in Hb Decreased serum haptoglobin Confirmed by positive Coomb’s test Resolves as transfused cells are removed Monitor Hb Maintain hydration Re-transfuse if necessary

Minor Allergic Reactions Allergic reactions to proteins in donor plasma cause urticarial reactions in 0.5 to 4% of all transfusions Most frequent in FFP or platelets Itching, swelling, rash Treat with diphenhydramine

Anaphylactic Reactions Seen typically in pt’s with hereditary IgA deficiency Previously sensitized during pregnancy or exposed to blood with foreign IgA Dyspnea, bronchospasm, angioedema, hypotension Discontinue transfusion Administer epinephrine and methylprednisolone

Febrile Reactions Pt’s who receive multiple transfusions of RBC’s will develop human leukocyte antigens (HLA) On subsequent RBC transfusions antibodies attack donor leukocytes causing febrile reactions Occur in up to 2% of platelet, FFP, and RBC transfusions Increase in temperature of more than 1 degree C with 4 hours of transfusion Defervesces within 48 hours Occasional chills, dyspnea, anxiety, headache, myalgia Treat with acetaminophen Differentiate with direct Coomb’s test

Transfusion-Related Acute Lung Injury TRALI is a noncardiogenic form of pulmonary edema occurring after blood product administration Associated with all plasma-containing components Estimated at 1:1271 to 1:5000 transfusions Mortality of at least 5%

Transfusion-Related Acute Lung Injury Occurs when mediators present in the plasma of donor blood activates leukocytes in the host Activated leukocytes are sequestered by the lungs Leukocyte mediators are released and cause increased capillary permeability and endothelial damage “two hit theory” Trauma, surgery, sepsis may first “prime” native granulocytes causing surface adhesion sites resulting lung sequestration Biologically active mediators that are breakdown products from cellular elements in blood products activate sequestered leukocytes

Signs and Symptoms Within 6 hours of transfusion Dspnea Chills Fever Noncardiogenic pulmonary edema/bilateral pulmonary infiltrates Hypotension/hypertension may occur

Diagnostic Criteria Acute onset of hypoxemia (within 6 hours of conclusion of transfusion) Bilateral CXR infiltrates consistent with ALI Absence of evidence of left atrial hypertension Absence of temporally related causes of ALI

Treatment Largely supportive Transfusion should be stopped if recognized in time Supplemental oxygen and ventilation support provided if necessary Use low tidal volume settings like in ARDS No diuretics Glucocorticoids have been administered but no evidence supporting their administration