OVERVIEW OF THE ARDP and TOOLS TO DETERMINE CLINICAL SIGNIFICANCE

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OVERVIEW OF THE ARDP andTOOLS TO DETERMINE
CLINICAL SIGNIFICANCE
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ARDPAmerican Rare Donor Program

• Cooperative program
• ARC
• AABB
• Members
• 40 ARC
• 41 non-ARC
• One international in Milan, Italy
• Sao Paulo, Brazil seeking membership

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ARDP Eligible Donors

• High prevalence antigen negative (
• Ex. Yt(a-), Lu(b-), hrB , Lan-, Vel-
• Must be typed for all common antigens with at
  least two sources of antisera

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ARDP Eligible Donors

• Multiple common antigen neg (A/O)
• - R1, R2, Ro or rr AND
• - K-1 AND
• - Fy(a-) or Fy(b-) AND
• - Jk(a-) or Jk(b-) AND
• - S- or s-

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ARDP Eligible Donors

• Where theres an AND theres always an
• OR

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ARDP Eligible Donorsmultiple antigen negative

• R1, R2 or rr AND
• K-1 AND
• Fy(a-b-)
• All negative antigens confirmed with at least two
  sources of antisera

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ARDP Eligible Donors

• IgA deficient
• IgA level
• two separate draw dates
• Very few labs screen for IgA
• Ability?
• Time?
• Staff?

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Donor RegistrationOverview
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Rare Donors Registered per ARDP Member
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Rare Donors by Category
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Patient Requests
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Fill Rates
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Fill Rates(All Patients vs. Patients with SCD)
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6
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9
86
85
N 1070
N 351
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International Requests2004 -2006
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Units Shipped Abroad 2004 -2006
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Unfilled Requests (2005)

• 10 requests for U-
• 6 requests for Di(b-)
• 5 requests for Lu(a-b-)
• 3 requests for At(a-), Hy-, hrB-, Ge-2
• 2 requests for Ge-2,-3, hrS-, Lan-, Cr(a-)
• 1 request for rr, Yt(a-), Jo(a-), McLeod

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Unfilled Requests (2006)

• 9 requests for U-
• 5 requests for Jk3
• 4 requests for hrS-
• 3 requests for Hy-, Lu(b-)
• 2 requests for Js(b-), Di(b-), Yt(a-),
• Gy(a-), Jo(a-), Cr(a-), rr
• 1 request for rr, Ge-2, Sc-1,-2, Ko

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ARDP Experience with Molecular Matching

• Numerous DO System antibodies (Do(a-) and Do(b-)
• Four hrB-
• hrB- E- Jk(b-)
• hrB- E- K-1 Jk(b-) S-
• hrB- D- E-
• hrB- C- E-
• PJ typing 200 AA donors (BioArray?)

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Clinically Significant

• An antibody capable of causing decreased
  survival of transfused red blood cells is
  considered clinically significant.

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Tools to Determine CS

• Assessment of free plasma hemoglobin
• 51Cr-labeled survival studies
• Chemiluminescence test (CLT)
• Antibody dependent cytotoxicity assay (ADCC)
• Monocyte monolayer assay (MMA)

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Assessment of Free Plasma Hgb

• Principle trial transfusion with small amount
  of blood check for hemolysis
• Transfuse 10-30 ml of blood slowly
• Draw tube of blood after 20 minutes and visually
  inspect for hemolysis

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51Cr Survival Studies

• Principle hemoglobin binds radiolabeled
  substance when incubated with red cells. Amount
  of 51Cr is quantified over time to determine
  survivability of allogeneic cells
• Large institutions blood volume studies
• Cell survival seldom performed
• Specialized technique little expertise
• JHH, UCLA

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CLT

• Principle Metabolic activation
• Measures the metabolic response of human
  monocytes to red cells sensitized with IgG
  antibodies
• CLT results are expressed as a percentage of the
  monocyte response to positive control cells.
  Results over 30 are consistent with moderate to
  severe disease
• Originated in Europe not done in US

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ADCC

• Principle cytotoxic lysis
• T lymphocytes bearing Fc receptors for
  immunoglobulin IgG lyse antibody-coated cells
• Originated in Europe not done in US
• May still be used in Europe

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MMA

• Principle red cells sensitized with CS antibody
  will adhere or be phagocytized by monocytes
  antibodies not CS will not bind
• Monocytes harvested from staff and bound to glass
  slide
• Antigen positive red cells are sensitized with
  test antibody
• Sensitized red cells are added to slide
• Incubate, wash, fix, stain
• Count reactive monocytes express as
• Positive - 3

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MMA Results GCP Antibodies
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Examples

• Unidentified antibody to high incidence antigen
  in Lutheran system
• Clinically significant?
• Transfusion reaction no to moderate
• HDN no to mild
• GCP experience patient JM CS with Lu(a-b)
  cells 6.6 9.5
• Transfuse Lu(a-b-) blood

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Examples

• Antibody that would not adsorb out unaffected by
  enzymes or AET Is it unidentified high
  incidence antibody or warm auto?
• Clinically significant?
• Transfusion reaction ?
• HDN ?
• GCP experience patient RB CS with
  phenotypically similar cells (4-8)
• Suggest MMA crossmatch for future transfusions

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MMA Important Points

• Each transfusion event can change an antibody of
  known specificity
• Broaden in specificity
• Clinical significance can change
• Extremely important to repeat MMA after each
  transfusion
• MMA can also be used to assess nonspecific
  reactivity or panagglutinin of unknown specificity

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Thank you for joining us today!