Leukocyte Reduction of Blood Components

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Leukocyte Reduction of Blood Components

• Ningli Cheng, MD
• Blood Bank Rotation
• 9-16-05

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Why do we use leukocyte reduced blood products?

• More than 90 of adverse reactions mediated by
  donor leukocytes
• Febrile nonhemolytic transfusion reactions
• Human leukocyte antigen alloimmunization
• Transfusion related acute lung injury
• Transfusion associated graft versus host disease
• Transfusion related immune suppression
• Transfusion-transmissible viral infection
• Harbor cytomegalovirus
• Epstein-Barr virus
• Human immunodeficiency virus
• Human T lymphotropic virus
• CJD-prion is associated with B-lympocytes

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Leukocytes (WBC) are present in varying
concentrations in all cellular blood components
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Febrile non-hemolytic reactions

• Febrile non-hemolytic reactions may be caused by
• interaction between patient antibodies and donor
  leukocytes leading to release of cytokines
• release of cytokines by recipient cells after
  interaction with antigen-antibody complexes
  consisting of donor leukocytes
• Febrile reactions to platelets are more likely
  with platelets that have been stored longer
• can be accounted for by cytokines released by
  white cells during storage of platelet
  concentrates

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TABLE. Results From 3 Recent Studies on NHFTR to
Red Cells and Platelets
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Refractory Platelet Transfusion

• Chronic transfusion Patients
• Most commonly due to antibodies directed against
  HLA Class I antigens
• HLA class I antigen expressed both on white cells
  and platelets.
• There is evidence that it is the leukocytes in
  platelet concentrates induce the formation of HLA
  antibodies

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FIGURE. Attenuation of alloimmunization-mediated
platelet refractoriness from the Trial to Reduce
Alloimmunization to Platelets (TRAP) study
N Engl J Med 1997 3371861-1869
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CMV Infection

• CMV and HTLV are transmitted exclusively by
  leucocytes
• 50-85 adults in USA are infected with CMV by the
  age of 40.
• In day care or preschool, 70 of children younger
  than 3 years of age have been infected with or
  are transmitting CMV.
• Once a person has had a first CMV infection, the
  virus lies dormant in cells in the body
  throughout life
• Less than 2 of healthy donors are able to
  transmit infection

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CMV Negative Blood

• CMV negative blood is labeled if the test is
  negative
• Most common methods of CMV testing
• EIA
• latex agglutination
• CMV antigen-coated latex particles
• It detects anti-CMV IgG or and anti-CMV IgM of
  patients serum
• Limitation of CMV negative blood
• Can not distinguish infective antibody-positive
  units from noninfective
• false negative
• Short of supply

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Method for decrease the incidence of
transfusion-transmitted CMV

• Use leukocyte-reduced blood components
• Blood. 1995 Nov 186(9)3598-603.
• Blood. 1996 Jun 187(11)4910
• Use CMV negative blood components

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Efficacy of Epstein-Barr virus removal by
leukoreduction of red blood cells

• 4-log reduction of EBV genomic copy number can be
  achieved with leukoreduction of RBC units and
  renders most RBC units EBV-negative by sensitive
  PCR.
• Transfusion. 2005 Apr45(4)591-5

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Depletion of Resident Chlamydia pneumoniae

• Leukoreduction with a filter is an effective
  method to significantly reduce resident C.
  pneumoniae levels in RBC components but may not
  be completely sufficient for total eradication of
  this pathogen
• J Clin Microbiol. 2005 Sep43(9)4580-4

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Pulmonary Tract Infections

• Reduced the incidence of pulmonary tract
  infections in patients undergoing coronary artery
  bypass grafting
• Acta Cardiol. 2005 Jun60(3)285-93
• Prestorage leukoreduction and low-temperature
  filtration reduce hemolysis of stored red cell
  concentrate
• Transfusion. 2005 Jan45(1)90-6

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Methods of Leukocyte Reduction

• Pre-storage carried out at the blood center
  shortly after or during collection
• After storage at the blood center but before
  issue
• Post-storage at bedside filtration
• Permit leukocytes reduced blood products
• countries

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Methods continue...

• Fourth generation filters
• remove 99.99 of the white cells
• Third generation filters
• less than 5 X 106 WBC
• Aapheresis devices
• less than 106 WBC
• Leukocytes reduced but not sufficiently effective
  or reliable
• Microaggregation filters
• Washing
• Freezing red cells

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Does it cost more to have blood filtered to
remove white blood cells?

• Adding 10 to 20 for filter to the cost of
  preparing blood.
• More than offsets the cost to leukocyte reduce by
  filtration.
• Cost savings in hospital charges
• Reduced patient hospital stay
• Saving the U.S. healthcare system six to twelve
  billion dollars per year for surgery patients
  alone

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TABLE. Established and Suspected Benefits to
Leukocyte Reduction Adapted From the Circular of
Information for the Use of Blood and Blood
Components
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Indications

• Established Indications
• Reducing recurrent febrile non-hemolytic
  transfusion reactions (FNHTR)
• Reducing CMV transmission by cellular blood
  components
• Reducing HLA alloimmunization

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Indications continue...

• patients receiving chemotherapy
• refractory to platelet transfusion
• multiple pregnancies
• chronic transfusion requirements
• immunosuppressed patients with CMV sero-negative
  test
• bone marrow transplant
• premature neonate or infants less then 4 months
• peripheral blood progenitor cell transplant
  candidate or recipient
• renal transplant candidate or recipient solid
  organ transplant recipient
• intrauterine transfusion
• hematologic malignancy

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Indications Under Review

• Prevent alloimmunization and the refractory state
  to platelets
• Reduce tumor recurrence rates after resection
• Reduce postoperative wound infections and
  mortality
• Prevent latent CMV reactivation
• Prevent latent HIV reactivation
• Prevent HLA alloimmunization in organ or bone
  marrow transplant candidates

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Indications Under Review

• Prevent transfusion-related acute lung injury due
  to passive administration of anti-leukocyte
  antibody
• Prevent anaphylactic (hypersensitivity)
  transfusion reactions
• Prevent hemolytic transfusion reactions
• Prevent transfusion-associated graft vs. host
  disease

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Precautions

• Filtration becomes less efficient when blood
  warms during transfusion,
• The process can only be quality-controlled on
  products at the Blood Center
• May cause hypotension in patients with ACE
  inhibitor
• The loss of 5-10 of the red cell pool is
  predicted

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Conditions for WhichLeukoreduction is Not
Indicated

• Not to be used for transfusion of granulocyte
  concentrates
• Cannot be relied on to prevent graft versus host
  disease (GVHD)
• Recipients at risk of GVHD receive products
  irradiated prior to transfusion
• bone marrow transplant recipients
• immuno-compromised patients
• recipients of transfusions from family members
• Ineffective in preventing transfusion related
  acute lung injury (TRALI)
• Does not prevent antibody mediated transfusion
  reactions such as hemolytic or hypersensitivity
  reactions

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TABLE. Countries That Have Mandated Universal
Leukocyte Reduction as a Matter of Public Blood
Safety Policy
Universal leucodepletion (ULD) has been
introduced in several countries
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ULD unresolved problems

• Complete protection from some viral transmission
  such as HTLV and CMV infections
• Reduction of bacterial sepsis
• Not fully abrogated FNHTR
• Further reduce some specific leucocyte subsets
• Their fragments as well as reduce the activation
  of coagulation/complement/kinin and inflammatory
  systems
• Reduce the rapid development of
  apoptotic/necrotic cells
• Transfusion and Apheresis Science 2003,Vol 29
  P105-117