Complications of Blood Transfusion: An Overview

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ISBT Human Blood Group Systems
Number Name Abbreviation 001 ABO ABO 002 MNSs MNSs
003 P P 004 Rh RH 005 Lutheran LU 006 Kell KEL 00
7 Lewis LE ( ABO Ag secretories) 008 Duffy FY
(resistancy to malaria in FY neg) 009 Kidd JK 010
Diego DI 011 Cartwright YT 012 XG XG 013 Scianna S
C 014 Dombrock DO 015 Colton CO 016 Landsteiner-Wi
ener LW 017 Chido/Rodgers CH/RG 018 Hh H 019 Kx XK
020 Gerbich GE 021 Cromer CROM 022 Knops KN 023 I
ndian IN 024 Ok OK 025 Raph RAPH 026 JMH JMH
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Blood Transfusion
Indication

• Acute massive blood loss
• Anaemia and hypoalbuminemia
• Overwhelming Infection
• Dysfunction of Coagulation

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Complications of Transfusion

• Transfusion reactions occur in 2 of units or
  within 24 hours of use.
• Most common adverse side effects are usually mild
  and non-life-threatening
• Two categories
• Infectious complications
• i.e HIV and HCV ? 1 transmission/2 million
  transfusion
• Non-infectious complications

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Non-infectious Complications of Transfusions

• Technical Manual
• Acute (lt 24)
• Immunologic
• Non-immunologic
• Delayed (gt 24)
• Immunologic
• Non-immunologic

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Acute (lt 24) Immunologic

• Hemolytic
• Fever/chills, non-hemolytic
• Urticarial/Allergic
• Anaphylactic

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Acute (lt 24) Non-Immunologic

• Transfusion-related acute lung injury (TRALI)
• Circulatory overload
• Nonimmune hemolysis
• Air embolus
• Hypocalcemia
• Hypothermia
• Acid/Base Disturbances
• Citrate Toxicity
• Coagulopathy

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Delayed (gt 24) Immunologic

• Allo-immunization
• RBC antigens
• HLA
• Hemolytic
• Graft-versus-host disease (GVHD)
• Post-transfusion purpura
• Immuno-modulation

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Delayed (gt 24) Non-Immunologic

• Iron overload

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Infectious complications

• Viral ( hepatitis, HIV, CMV, HTLV)
• Parasitic and bacteremia (especially
  platelets)

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Acute (lt 24) Immunologic

• Hemolytic
• Fever/chills, non-hemolytic
• Urticarial/Allergic
• Anaphylactic

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Hemolytic

• Most severe hemolytic reactions, occur when
  transfused RBCs interact with preformed Ab
• Transfused Ab reactions, with recipients RBCs
  rarely cause sxs.
• May cause accelerated RBC destruction
• Can occur after infusion of as little as 10-15 mL
  ABO-incompatible blood
• Etiology
• 138,000 to 170,000
• Clerical and other human error most common causes
  of ABO-incompatible transfusion
• Mortality estimated to be 11,000,000 transfusion
• Highly variable in acuity and severity
• Severity of the reaction depends in the
  amount of blood given
• Severe
• Fevers and/or chills, Hypotension, Dyspnea,
  Tachycardia
• Pain, DIC, Shock, Rise in temperature, renal
  failure

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Hemolytic

• Pathophysiology
• Intravascular hemolysis, opsonization, generation
  of anaphylotoxins
• Complement activation ? classical pathway
• IgM and IgG
• C1q binds to Ig
• C3 activation ? cleavage of C3 leads to C3a being
  released into plasma and C3b deposition onto RBC
  membrane
• C3a ? proinflammatory effects
• C3b ? erythrophagocytosis
• C5 cleaved ? C5a into plasma
• C5a ? proinflammatory (100-fold more potent than
  C3a)
• Assembly of remaining components of the MAC then
  occurs on RBC surface
• Lysis of RBC
• Cytokines activation
• TNF, IL-1, IL-6, IL-8
• Coagulation activation
• Bradykinin

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Hemolytic

• Laboratory findings
• Hemoglobinemia
• Hemoglobinuria
• ? LDH
• Hyperbilirubinemia
• ? Haptoglobin
• ? BUN, creatinine in ARF (Aggressive Fluid
  Resuscitation)
• DAT

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Hemolytic

• Differential diagnosis
• AIHA (Auto immune hemolytic anemia)
• Nonimmune hemolysis
• Microangiopathic hemolytic anemia
• Drug-induced
• Infections
• Any causes of hemolysis

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Hemolytic

• Treatment/Prevention
• Stop transfusion
• Supportive care to maintain renal function
• Goal of urine O/P 100 mL/hr. in adults for at
  least 18-24 hours
• Low dose dopamine
• Treatment of DIC
• ? Heparin direct anticomplement effect
• Prevention of clerical/human errors
• Double Check name, type and crossmatch
• Temperature Monitor

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Acute (lt 24) Immunologic

• Hemolytic
• Fever/chills, non-hemolytic
• Urticarial/Allergic
• Anaphylactic

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Fevers/chills, non-hemolytic (FNHTR)

• Defined as a rise in temperature of 1C or
  greater.
• Incidence
• 43-75 of all transfusion reaction.
• PRBCs 0.5-6
• Plts 1-38
• Signs/Symptoms
• Chills/rigor
• HA
• Vomitting

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Fevers/chills, non-hemolytic (FNHTR)

• Etiology
• Reaction
• Between recipient antibodies against transfused
  WBC (HLA, WBC antigens) in product
• Cytokines that accumulates in blood bag during
  storage
• Differential Diagnosis
• Other causes of fever ruled out
• Hemolytic
• Bacterial/Septic
• Treatment/Prevention
• Discontinue transfusion
• Acetaminophen/meperidine
• Leukoreduced blood component

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Acute (lt 24) Immunologic

• Hemolytic
• Fever/chills, non-hemolytic
• Urticarial/Allergic
• Anaphylactic

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Uritcarial/Allergic

• Continuum
• Mild urticarial
• Anaphylactoid
• Severe anaphylactic
• Incidence
• 1-3 of all transfusion reaction.
• Signs/Symptoms
• Uriticarial/hives upper trunk and neck
• Fever
• Pulmonary signs (10) hoarseness, stridor,
  lump in throat, bronchoconstriction
• No cutaneous involvement
• GI pain, diarrhea
• Circulatory tachycardia, hypotension

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Uritcarial/Allergic

• Etiology
• Circulating Ab against soluble material in the
  blood
• Proteins in donor plasma
• Binds to preformed IgE Ab on mast cells
• Release of histamine
• Vasoactive substances
• C3a, C5a, leukotrienes
• Differential Diagnosis
• Hemolytic
• Bacterial
• TRALI
• Treatment/Prevention
• Discontinue transfusion
• Antihistamine/steroids
• Washing of blood products, pretreatment,
  leukoreduction?

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Acute (lt 24) Immunologic

• Hemolytic
• Fever/chills, non-hemolytic
• Urticarial/Allergic
• Anaphylactic

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Anaphylactic

• Rare
• Incidence
• 118,000 to 170,000
• Plt 11598-9630
• FFP 128,831
• RBCs 123,148-57,869
• Signs/Symptoms
• In addition to uritcarial/allergic
• Cardiovascular instability
• Cardiac arrhythmia
• Shock
• Cardiac arrest
• More pronounced respiratory involvement

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Anaphylactic

• Etiology
• IgA Ab (IgE, IgG, IgM) in IgA deficiency
• Serum IgA lt 5 mg/dL
• Estimated 1 in 342 blood donors
• C4 Ab
• Ab against nonbiologic origin
• Haptoglobin deficiency (IgG or IgE
  anti-haptoglobin)
• Differential Diagnosis
• Hemolytic
• Bacterial
• TRALI
• Circulatory overload

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Anaphylactic

• Treatment/Prevention
• Discontinue transfusion
• Supportive care
• Epinephrine
• Antihistamine/steroids
• In IgA deficient pts. ? IgA-deficient product,
  wash blood product

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Delayed (gt 24) Immunologic

• Allo-immunization
• Hemolytic
• Graft-versus-host disease (GVHD)
• Post-transfusion purpura
• Immuno-modulation

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Allo-immunization

• Occurs weeks to months after transfusion
• Incidence
• 1-1.6 to RBC antigens
• 10 to HLA
• Signs/Symptoms
• PRBCs ? hemolysis
• Plts. ? refractoriness
• Treatment/Prevention
• Plts.
• Leukoreduction
• Cross-matched and/or HLA-matched plts.

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Delayed (gt 24) Immunologic

• Allo-immunization
• Hemolytic
• Graft-versus-host disease (GVHD)
• Post-transfusion purpura
• Immuno-modulation

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Hemolytic

• Once allo-immunization has occurred, Abs may
  diminish to undetectable levels or Caused by
  antibodies to non-D antigens of the Rh system or
  foreign alleles
• Especially Kidd system (anti-Jka and anti-Jkb)
• Hemolysis typically extravascular
• Anamnestic response
• Within hours or days (up to 6 weeks), IgG Ab
  reacts with transfused red cells
• Prospective study
• 58 of 2082 (2.8) RBC recipients were found to
  have alloAbs (previous undetected) w/in 7 days of
  transfusion
• Not be preventable
• High risk
• Previous blood transfusions
• Pregnancy
• females who have a known disposition of
  alloimmunization
• Incidence
• Based on above study, only 1 recipient with new
  Ab w/in 7 days of transfusion was shown to have
  hemolysis
• Estimated rate
• 1 in 2082 recipients
• 1 in 11,328 units

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Hemolytic

• Signs/Symptoms
• Fever
• Declining Hb and hematocrit value
• Mild jaundice
• Hemoglobinuria
• ARF uncommon
• Check for alloAb in both serum and RBC (Coombs
  test)
• Treatment/Prevention
• Rarely necessary
• May need to monitor urine O/P, renal function,
  coagulation functions
• IVIG
• Appropriate units for transfusion

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Delayed (gt 24) Immunologic

• Allo-immunization
• Hemolytic
• Graft-versus-host disease (GVHD)
• Post-transfusion purpura
• Immuno-modulation

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Graft-versus-host disease (GVHD)

• Fatal complication cause by engraftment and
  clonal expansion of donor lymphocytes in
  susceptible host
• Attack recipient tissues
• Immunocompromised pts.
• Hematologic malignancies or certain solid tumors
  receiving chemotherapy radiation
• Stem cell transplant
• Recipients of HLA matched products or familial
  blood donation
• Lupus or CLL requiring fludarabine
• Not reported in AIDS pts.
• 2-30 days after transfusion
• Incidence
• Rare (0.002-0.005)

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GVHD

• Signs/Symptoms
• Appears w/in 10-12 days of transfusion
• Skin whole body erythroderma, desquamation
• GI ? N/A, diarrhea
• Liver
• BM ? failure leading to pancytopenia
• Treatment/Prevention
• No effective treatment
• Gamma irradiation
• Render T-cells incapable of replication
• FDA requirement
• Minimum of 2500 cGy target to the midline of the
  container
• Minimum of 1500 cGy target to all other part of
  component

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Delayed (gt 24) Immunologic

• Allo-immunization
• Hemolytic
• Graft-versus-host disease (GVHD)
• Post-transfusion purpura
• Immuno-modulation

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Post-transfusion Purpura (PTP)

• Characterized by abrupt onset of severe
  throbocytopenia (lt 10 K)
• Average of 9 days (range 1-24 days)
• PRBCs or whole blood
• Reported in plts., plasma, frozen deglycerolized
  PRBCs
• Incidence
• Rare
• Over 200 cases published
• MaleFemale 15
• Median age 51 years (range 16-83)
• Clinical course
• Usually self-limited, recovery w/in 21 days
• 10-15 mortality
• Intracranial hemorrhage

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PTP

• Signs/Symptoms
• Profound thrombocytopenia
• Purpura
• Bleeding
• Fever (reported)
• Etiology
• Plt. specific IgG Ab that are auto-Ab
• All HPA implicated but HPA-1a most common
• 3 mechanisms
• Immune complex pt. Ab and donor antigen
• Concersion of antigen- autologous plts. to Ab
  targets to antigen in transfused components
• Cross-reactivity of pts. autoAb with autologous
  plts.

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PTP

• Differential diagnosis
• ITP
• TTP
• Alloimmunization
• Sepsis
• DIC
• BM failure
• Drug-induced
• Treatment/Prevention
• Steroids controversial
• Plasma exchange achieves plts. counts to 20K in
  1-2 days (up to 12 days)
• IGIV recovery of plts. Counts of 100K w/in 3-5
  days
• Block Ab-mediated clearance
• Splenectomy refractory pts., high risk of
  life-threatening hemorrhage
• Plts. transfusion not effective
• Antigen-negative blood product

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Delayed (gt 24) Immunologic

• Allo-immunization
• Hemolytic
• Graft-versus-host disease (GVHD)
• Post-transfusion purpura
• Immuno-modulation

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Immuno-modulation

• ? Increases risk of recurrent cancer and
  bacterial infection
• WBCs ? cytokines during storage ? interfere with
  immune function
• Uncertain clinical significance
• Leukoreduction of blood products