NICHOLAS TSU, M.D.

Transfusion Reactions

Objectives

Transfusion statistics and basicsTypesDiagnosisTreatment

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 Viral Bacterial

Noninfectious 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 floraDonor bacteremiaContamination from

Collection Processing Storage

Signs and Symptoms of Bacterial Infection

FeversChillsTacycardiaDyspneaEmesisShockDICAcute renal failure

Diagnosis and Treatment

Stop transfusionObtain blood culturesTreat with broad spectrum antibioticsNotify the blood bank immediately

Prevent other units from same donor being transfused

Acute Hemolytic Transfusion Reactions

Most hazardous against foreign RBC’sHemolysis of donor RBC’s can lead to ARF &

DICMortality rate is 2%Leading cause is clerical error

Acute Hemolytic Transfusion Reactions

Over 300 antigens on human RBC’sMost 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 initiallyWill circulate unbound until excreted by

kidneysRenal 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

FeverChillsNausea and vomitingDiarrheaRigorsHypotension and tachycardia (bradykinin)Flushed and dyspneic (histamine)Chest and back pain (cytokine release)HeadacheFeeling of impending doomHemoglobinuria eventually oliguria

Diagnosis

Stop transfusionRecheck patient and unit labelingExamine centrifuged plasma sample for pinkish

discoloration representing free HbHemolysis should be assumed to be hemolytic

transfusion reaction until proven otherwiseNotify blood bankAseptically seal unit and returnCoombs 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 feverIncreased indirect bilirubinUnexplained reduction in HbDecreased serum haptoglobinConfirmed by positive Coomb’s testResolves as transfused cells are removedMonitor HbMaintain hydrationRe-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 plateletsItching, swelling, rashTreat 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 transfusionAdminister 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 hoursOccasional chills, dyspnea, anxiety, headache,

myalgiaTreat with acetaminophenDifferentiate 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 transfusionsMortality 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 lungsLeukocyte 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 ALIAbsence of evidence of left atrial

hypertensionAbsence of temporally related causes of ALI

Treatment

Largely supportiveTransfusion should be stopped if recognized

in timeSupplemental 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