Terry Kotrla, MS, MT(ASCP)BB

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Unit 12 Adverse Complications of Blood Transfusion

• Terry Kotrla, MS, MT(ASCP)BB

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Introduction

• Transfusion of blood and blood components safe
  and effective way to correct hematologic
  deficits.
• Complications during transfusion may occur,
  called transfusion reactions and include broad
  range of events and problems.
• Some reactions preventable, some are not.
• Risk of transfusion must be weighed against
  benefits.
• Two categories
• Acute or immediate reactions
• Delayed reactions

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Clinical Evaluation of Transfusion Reaction

• Time between reaction and investigation must be
  as short as possible.
• Two pronged evaluation
• Clinical evaluation of patient
• Laboratory investigation and testing
• Responsibility of initiation rests with
  transfusionist.

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Procedure for Transfusion

• Blood product picked up from transfusion service.
• Two licensed personnel check forms against blood
  product label and patient armband.
• Take vital signs.
• Start transfusion.
• If possible stay with patient first 15 minutes.
• Retake vital signs to ensure no change.
• If the same continue transfusion which must be
  completed within 4 hours, shorter time is
  preferable, usually 2 hours.
• Check on patient periodically.
• Take vital signs upon completion of transfusion

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What to Watch for During Transfusion

• Fever
• Chills
• Abdominal, chest, flank or back pain
• Hyper- or hypotension
• Nausea/vomiting
• Skin manifestations urticaria, rash, flushing,
  pruritus and localized edema.
• Respiratory distress wheezing, coughing and
  dyspnea
• Jaundice or hemoglobinuria
• Abnormal bleeding or generalized bleeding (DIC)
• Oliguria or anuria
• Pain or burning at infusion site.
• Shock

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Actions for Complications

• Any sign or symptom must be considered
  potentially life-threatening.
• Fever and chills may simply be a benign reaction
  or an indication of acute hemolysis.
• Two areas of action for the transfusionist
• Patient focused steps
• Component focused steps

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Patient Focused Steps

• Stop the transfusion immediately to limit the
  amount of blood infused and notify a responsible
  physician.
• Keep the IV line open with infusion of normal
  saline.
• At the patient's bedside perform clerical recheck
  between the patient and component check all
  labels, forms and patient identification to
  determine if the patient received the intended
  component.
• Notify patients physician immediately.

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Component Focused Steps

• Contact transfusion service immediately.
• Return discontinued bag of blood, the
  administration set without the IV needle,
  attached IV solutions and all the related forms
  and labels.
• Send required blood samples, carefully drawn to
  avoid mechanical hemolysis, to the transfusion
  service as soon as possible.
• Send other blood samples for evaluation of acute
  hemolysis as directed by the transfusion service
  director or patient's physician.

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Laboratory Investigation

• Handle STAT each and EVERY time!!
• Clerical check identification of patient blood
  sample, labels, paperwork and donor blood.
• Repeat ABO testing on the post-transfusion
  sample.
• Visual check comparing the patient's
  pretransfusion and post-transfusion specimen for
  color of serum or plasma.
• Perform a DAT on the post-transfusion specimen.
• If all are negative or normal, nothing further
  needs to be done.

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Additional Laboratory Tests for AHTR

• If DAT positive or hemolysis present in
  post-transfusion sample additional testing must
  be performed.
• Repeat ABO/D on patient pre- and post-transfusion
  samples as well as donor.
• Repeat antibody screen on pre- and
  post-transfusion samples.
• Repeat crossmatch on pre- and post-transfusion
  samples THROUGH AHG.
• If tests on pre-transfusion sample do not match
  post-transfusion sample notify blood bank
  supervisor or medical director AND patients
  physician.

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Investigation for Non-Immune Hemolysis

• Consider bacterial contamination of the donor
  unit if
• The cells or plasma have brownish or purple
  discoloration.
• There are clots or abnormal masses in the liquid
  blood or segments closest to primary bag appear
  hemolyzed.
• The plasma is opaque or muddy.
• There is a peculiar odor.
• If any of these are notated set up cultures at 4
  C, 20-24 C and 35-37 C and perform a gram stain
  on the unit.

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Investigation for Non-Immune Hemolysis

• Examine the supernatant plasma from the donor
  blood container for presence of free hemoglobin.
• Examine the blood remaining in the administration
  tubing for presence of free hemoglobin.
• Consider the possibility that the patient or
  donor has an intrinsic RBC defect such as G-6-PD
  deficiency or PNH.
• Consider the possibility of mechanical hemolysis.
• Consider osmotic hemolysis due to inadvertent
  entry into the circulation of hypotonic fluids

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Laboratory Evaluation Hemolysis Proven

• Examine post-transfusion urine specimens for the
  presence of free hemoglobin.
• Test post-transfusion serum samples for
  unconjugated bilirubin, carefully recording the
  timing of sample collection. Peak levels occur
  at 5-7 hours and disappear within 24 hours.
• Measure serum haptoglobin in pre- and
  post-transfusion specimens.

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Hemolysis Suspected But Tests Uninformative

• Perform antibody detection tests with more
  sensitive methods.
• Perform DAT and IAT daily or more frequently.
• Measure HH at frequent intervals to document
  rise or decrease.
• Type cells of recipient and donor to find
  antigens present on donor but absent on
  recipient.
• If hemoglobinopathy present perform hemoglobin
  electrophoresis to verify presence of normal
  hemoglobin.

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Acute Hemolytic Transfusion Reaction

• Triggered by antigen-antibody reaction which
  activates complement, coagulation systems and
  endocrine response.
• Catastrophic clinical events may occur
• Shock
• DIC
• Acute renal failre
• Life threatening AHTRs almost always due to ABO
  mismatch.
• Other blood group incompatibilities may cause
  hemolysis usually not as severe as ABO.

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Acute Hemolytic Transfusion Reaction

• Diagnosis
• Most common initial sign is FEVER.
• Reaction may occur with as little as 10-15 mL of
  incompatible blood.
• Onset symptoms may be mild vague uneasiness,
  abdominal, chest, flank or back pain.
• First sign patient observes is red or dark urine
  with or without back pain.
• Severity directly related to amount of blood
  transfused.
• Anesthetized bleeding at surgical site,
  hypotension or presence of hemoglobinuria.
• STOP TRANSFUSION, keep IV line open.

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Therapy for AHTR

• Goal to treat hypotension and promote renal blood
  flow.
• Hemoglobin toxic to kidneys, give fluids to
  maintain urine output, diuretics to promote urine
  formation.
• DIC may occur.
• Consult with appropriate medical specialist to
  ensure appropriate treatment.

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Prevention of AHTRs

• Impossible
• Hemolysis may occur even if crossmatch compatible
  anamnestic response.
• Human error
• Wrong sample from wrong patient.
• Tech mixed up samples.
• Blood transfused to wrong patient.
• SOPs MUST BE FOLLOWED BY EVERYONE.
• Fatalities must be reported to FDA within 24
  hours.

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Other Immediate Complications

• Febrile non-hemolytic
• Transfusion related sepsis
• Allergic reactions
• Transfusion associated circulatory overload
  (TACO)
• Transfusion related acute lung injury (TRALI)
• Massive transfusion

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Febrile non-hemolytic

• Rise in temperature of 1C or 2F in association
  with transfusion and no other identifiable cause.
• Caused by antibodies to transfused lymphs, grans
  or platelets.
• Usually occur in repeatedly transfused or
  pregnant patients.
• Usually benign BUT may be first sign of AHTR.
• STOP TRANSFUSION and initiate work up
• Prevention pre-storage leukoreduction has
  decreased incident.
• Pre-medicate with antipyretics NOT aspirin.

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Transfusion Related Sepsis

• Signs/symptoms which occur during or shortly
  after transfusion.
• Fever, particularly 101F
• Shaking chills
• Hypotension
• STOP TRANSFUSION IMMEDIATELY START WORK UP
• May progress to shock, hemoglobinuria, DIC and
  renal failure.
• Platelets most frequently implicated
• Life threatening sepsis due to platelet
  transfusion 1 in 100,000
• Immediate fatal outcome due to platelet
  transfusion 1 in 500,000

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Transfusion Related Sepsis

• Bacteria may enter component containers or
  contaminate port of bag during
• donor phlebotomy or
• component preparation.
• Most common infectious hazard of transfusion.

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Transfusion Related Sepsis

• Components from same donation may be
  contaminated.
• Platelets most commonly implicated.

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Transfusion Related Sepsis

• Each unit must be inspected prior to issue.
• Quarantine if
• Purple color,
• clots in bag
• hemolysis, especially sprigs closest to primary
  bag.

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Allergic Reactions

• Urticaria
• Commonly encountered
• Characterized by local erythema, hives and
  itching, usually without fever or other
  complications.
• If localized urticaria is the only manifestation,
  it is usually not necessary to discontinue the
  transfusion.
• Etiology unknown
• Pre-treat with antihistamines.

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Allergic Reactions

• Anaphylactic Shock
• Occurs after the infusion of only a few
  milliliters of blood or plasma and the absence of
  fever.
• Onset characterized by coughing, broncho spasm,
  respiratory distress, vascular instability,
  nausea, abdominal cramps, vomiting, diarrhea,
  shock and loss of consciousness.
• Reactions may occur in IgA deficient patients who
  have developed anti-IgA antibodies after
  immunization by previous transfusion or
  pregnancy.
• STOP TRANSFUSION IMMEDIATELYSTART WORK UP
• Sensitized IgA-deficient patients must be
  transfused with blood and blood components that
  lack IgA.

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Transfusion Associated Circulatory Overload (TACO)

• Hypervolemia must be considered if dyspnea,
  severe headache, peripheral edema or other signs
  of congestive heart failure occur during or soon
  after transfusion.
• Rapid increases in blood volume poorly tolerated
  by patients with compromised cardiac or pulmonary
  status.
• Symptoms coughing, cyanosis, orthopnea,
  difficulty breathing.
• STOP TRANSFUSION IMMEDIATELYSTART WORK UP
• For susceptible patients give small volumes
  SLOWLY.

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Transfusion Related Acute Lung Injury (TRALI)

• Number 1 cause of transfusion related deaths.
• Chest x-ray acute pulmonary edema, acute
  respiratory insufficiency but no evidence of
  heart failure.
• Symptoms of RDS after infusion of volumes to
  small to produce hypervolemia.
• May be accompanied by chills, fever, cyanosis and
  hypotension.
• Occurs within 6 hours of transfusion, most within
  1-2 hours after transfusion.
• One study 100 of patients require O2, 72 of
  those require mechanical ventilation as well.

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Transfusion Related Acute Lung Injury (TRALI)

• All plasma products have been implicated.
• Reaction between DONOR leukocyte antibodies and
  recipient as well as biologically active lipids.
• WBCs aggregate, trapped in lungs, release
  cytokines which damage and cause fluid to enter
  alveoli spaces.
• STOP TRANSFUSION IMMEDIATELYSTART WORK UP
• Treatment IV steroids and respiratory support.
• PREVENTION Do not make plasma products from
  female donors.

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Complications of Massive Transfusion

• Citrate toxicity
• Hemostatic abnormalities
• Hyperkalemia
• Hypocalcemia
• Air embolism
• Hypothermia

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Transfusion-Related Fatalities by Complication,
FY2005 through FY2009
TRALI HTR Non-ABO HTR (ABO) Microbial Infection TACO Anaphy Other
FY05 29 16 6 8 1 0 2
FY06 35 9 3 7 8 1 0
FY07 34 2 3 6 5 2 0
FY08 16 7 10 7 3 3 0
FY09 13 8 4 5 12 1 1
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Delayed Hemolytic Transfusion Reaction (DTR)

• Two types
• Due to primary response
• Due to secondary response

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DTR Primary Immune Response

• This is the immunizing event, takes weeks to
  months.
• As antibody titer increases in titer and avidity
  reacts with antigen positive donor cells present.
• Degree of hemolysis depends on
• Quantity of antibody present
• Quantity of antigen positive donor cells present.
• Usually unsuspected clinically but may suspect
  based on
• Unexplained fall in hemoglobin
• Positive DAT
• Appearance of new alloantibody

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DTR Secondary Immune Response

• Previously immunized individual.
• Alloantibodies may fall to undetectable levels.
• Kidd antibodies most common.
• Pre-transfusion testing reveals no unexpected
  antibodies.
• Within 3-7 days after transfusion anamnestic
  response
• Large number of antigen positive red cells
  present.
• Rapid increase in antibody titer
• Symptoms fever, unexplained fall in hemoglobin,
  jaundice.
• RARELY hemoglobinuria and renal failure.

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Detection of DTR

• Transfusion service may diagnose if another
  crossmatch is ordered.
• Current sample may have positive DAT.
• Perform elution
• Identify antibody
• Antibody screen
• May be negative, all antibody produced going onto
  donor rbcs
• Will become positive once all donor antigens
  coated.
• Reason that sample for compatibility testing be
  no more than 3 days old at time of testing.
• ALWAYS CHECK PATIENT HISTORY - Once immune
  antibody identified must ALWAYS give antigen
  negative blood even if antibody screen is
  negative.

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DTR
Antibody Screen DAT
Initial Negative NA
Next Sample Negative Positive- as antibody produced going on to donor rbcs
Next Sample Positive all antigen sites coated, excess antibody detectable Positive
Next Sample Positive Negative no donor cells left
Next Sample Negative Negative
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Infectious Complications

• Viral hepatitis
• Cytomegalovirus
• Malaria
• Babesiosis
• Syphilis
• Chagas Disease
• Toxoplasmosis
• West Nile Virus
• Human Immunodeficiency Virus
• Many more.

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Hepatitis

• Transmission of Hepatitis A rare fecal-oral
  route of transmission.
• All donors screened for Hepatitis B and C but
  transmission does occur not through window.
• Defer donor if only unit given patient contracted
  hepatitis.
• Defer donor if implicated in two cases.
• Identified by look back
• Still have non-A, B, C hepatitis transmission

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Infectious Disease Transmission

• Cytomegalovirus (CMV)
• Immunoincompetent/immunosuppressed.
• Transmitted by leukocytes.
• All blood pre-storage leukoreduced.
• Malaria no screening test available.
• Very rare but cases are rising.
• Travel and immigration.
• Exclude donors at high risk.
• Report cases to transfusion service or blood
  provider

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Infectious Disease Transmission

• Babesiosis
• Caused by Babesia species transmitted by ticks.
• Organism multiplies in RBCs.
• Donors permanently deferred.
• Syphilis
• Caused by Treponema pallidum
• Donor must be drawn during brief period of
  spirochetemia.
• Treponemes can only survive 72 hours at 4C.
• Serological test for syphilis (STS) negative in
  primary syphilis.
• Positive STS indicates high risk life style
  activities.

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Infectious Disease Transmission

• Chagas Disease
• Trypanosoma cruzi transmitted by reduviid bug.
• Disease primarily found in Central south
  America.
• Few cases reported in Texas and California.
• Cause of 30 of adult deaths in brazil.
• Toxoplasmosis
• Toxoplasma gondii
• Unusual complication in immunosuppressed
• Lymes disease
• Borrelia burgdorferi transmitted by tick bite.
• May be potential problem, no cases reported.

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Infectious Disease Transmission

• West Nile Virus
• Primary reservoir birds, spread by mosquitos.
• First documented transfusion cases 2002, 23
  cases.
• NAT test used to screen donors.
• Three month deferral after illness.
• Humon Immunodeficiency Virus
• Attempts to prevent transmission rely on careful
  donor screening and sensitive tests.
• No cure
• Transfusions should never be given unless
  medically necessary.

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Other Delayed Adverse Affects

• Transfusion Associated Graft versus Host Disease
  (TA-GVHD)
• Rare but usually fatal disease in
  immunosuppressed.
• Donor lymphocytes engraft in recipient, consider
  recipient foreign, mount immune response.
• Pretransfusion irradiation to prevent disease for
• Intrauterine transfusions
• Patients identified as being at risk for TA-GVHD
• Cellular components donated from relatives.
• Transfusion of HLA selected products.

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Other Delayed Adverse Affects

• Post-Transfusion Purpura
• Rare event occurring almost exclusively in
  multi-parous women.
• Precipitous fall in platelet count with purpura
  about 1 week after transfusion.
• Some caused by anti-HPA-1a
• Antigen has 98.3 prevalence, only 1.7 at risk.
• Antibody destroys not only transfused HPA-1a
  positive platelets but patients own HPA-1a
  negative platelets.
• Thrombocytopenia severe, platelet transfusions no
  help.
• Self-limiting.
• Exchange plasmapheresis for treatment.

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Adverse Complications of Transfusions
Immunologic Non-Immunologic Infectious
Alloimmunization TACO Hepatitis
Hemolytic Transfusion Rxn Massive Transfusion Metabolic Hypothermia Dilutional Pulmonary Microembolism HIV, HTLV
Febrile Transfusion Rxn Massive Transfusion Metabolic Hypothermia Dilutional Pulmonary Microembolism CMV, EBV
TRALI Massive Transfusion Metabolic Hypothermia Dilutional Pulmonary Microembolism Bacterial
Allergic Transfusion Rxn Massive Transfusion Metabolic Hypothermia Dilutional Pulmonary Microembolism Syphilis
Posttransfusion Purpura Massive Transfusion Metabolic Hypothermia Dilutional Pulmonary Microembolism Parasites
Immunosuppressive Effects
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End of Unit 12