2 In - SABM - Patient Blood Management

Accessing Rare
Blood Through
the American Rare
Donor Program (ARDP)
Cindy Flickinger, MT(ASCP)SBB
Director, Technical Services/National Reference Laboratory for Blood
Group Serology (NRLBGS)
Program Manager, American Rare Donor Program (ARDP)
The need is constant.
The gratification is instant.
Give blood.
TM

Objectives
•Provide overview of the ARDP
•Illustrate the steps used in the search
process
•Review program metrics
•Discuss challenges to providing rare
blood
•Describe impact of molecular testing
•Review ARDP-related case studies
The need is constant.
The gratification is instant.
Give blood. TM

Overview –ARDP
Collaborative program formed to provide rare
blood components to patients in need
Merger of AABB/ARC rare donor databases in 1998
82 ARC/AABB-accredited reference laboratories
Database
Donor side
Patient side
Search Process
Rare donors are submitted
Rare patient requests are submitted
Search for rare units to match patient needs
The need is constant.
The gratification is instant.
Give blood. TM

ARDP Member IRLs by State (82)
≥ 4 ARDP Members per State
3 ARDP Members per state
2 ARDP Members per State
1 ARDP Member per State
6
1
1
1
3
1
1
2
1
2
1
1
2
1 each
3
3
Italy, Brazil, Kuwait
3
The need is constant.
The gratification is instant.
Courtesy G. Meny
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1
1
3
2
2
2
2
3
2
2
4
5
3
3
3
3
PR
1
1
1
3
1

ARDP Criteria for Rare
Negative for high-prevalence antigen
(

Active Donors vs Requests (%)*
%
100
90
80
70
60
50
40
30
20
10
0
91.5
66.9
30.7
8
3.4
0.5
Highs Phenos IgA
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Total
Donors 48007 3840 43927 240
Patient requests 5069 3392 1555 122
* Data as of 12/2010

Search Process
ARDP member faxes request to ARDP site
Request is faxed to members with registered
donors of requested phenotype
Members with units respond---units are shipped
Shipping information is entered into database
Members act as portals to non-members
The need is constant.
The gratification is instant.
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Search Process (cont.)
If units are not found, fax is sent to all members
If units are not found, initiate recruitment
If recruitment is ineffective, initiate international
search
The need is constant.
The gratification is instant.
Give blood. TM

Search Process--International
Follow FDA regulations
Physician must sign letter with patient need
and understanding of the following:
Must search within the US before looking
international
Imported units considered ―unlicensed‖/‖untested‖
Imported units cannot be transfused to any other
patient or used for any other purpose
The need is constant.
The gratification is instant.
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Goal of ARDP
Meet transfusion needs of patients with
rare antibodies
Donors
↑ rare donor submissions
Patient requests
↓ unfilled requests
The need is constant.
The gratification is instant.
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Unfilled vs. Filled Requests
Number
3500
3000
2500
2000
1500
1000
500
0
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highs phenos IgA
Unfilled requests 282 (8.3%) 30 (1.9%) 0
Filled requests 3110 (91.7%) 1525 (98.1%) 122
Total requests 3392 1555 122
* Data as of 12/2010

Requests for High-Prev Ag Negative
Number requests
D+ U-
Yt(a-)
Js(b-)
k-
Rare Rh
Lu(b-)
Vel-
Kp(b-)
D- U-
E- hrB-
Jk:-3
Lu(a-b-)
Ge:-2
Co(a-)
Di(b-)
Hy-
PP1Pk-
Jo(a-)
Ge:-2,-3
Lan-
I-
Bombay
At(a-)
E- hrS-
Jr(a-)
Cr(a-)
Rare Kell
Sc:-1
Tc(a-)
Gy(a-)
Sc:-1,-2
In(b-)
Wes(b-)
2005 to 2010
700
600
500
400
300
200
100
0
The need is constant.
The gratification is instant.
Give blood. TM

Requests vs. Filled Requests for Highs
D+ U-
Yt(a-)
Js(b-)
k-
Rare Rh
Lu(b-)
Vel-
Kp(b-)
D- U-
E- hrB-
700
600
Number requests
500
Number requests filled
400
300
200
100
0
# unfilled 22 20 11 0 14 6 5 2 22 21
% unfilled 3.4 3.6 3.2 0 7.3 3.3 3.4 1.4 17.3 16.5
# donors 846 297 531 951 257 286 128 150 65 185
The need is constant.
The gratification is instant.
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Jk:-3
Lu(a-b-)
Ge:-2
Co(a-)
Di(b-)
Jo(a-)
Ge:-2,-3
Hy-
PP1Pk-
Lan-
Requests vs. Filled Requests for Highs cont.
90
80
70
60
Number requests
Number requests filled
50
40
30
20
10
0
# unfilled 16 10 8 1 16 10 1 5 12 8
% unfilled 19.7 15.3 12.5 1.9 30.1 18.8 3.1 17.2 42.8 29.6
# donors 23 43 18 137 25 27 35 25 8 13
The need is constant.
The gratification is instant.
Give blood. TM

I-
Bombay
At(a-)
E- hrS-
Jr(a-)
Cr(a-)
Rare Kell
Sc:-1
Tc(a-)
Gy(a-)
Sc:-1,-2
In(b-)
Wes(b-)
Requests vs. Filled Requests for Highs cont.
30
25
20
Number requests
Number requests filled
15
10
5
0
# unfilled 1 0 12 10 7 11 4 5 3 3 2 2 1
%
unfilled
4.1 0 54.5 47.6 38.8 78.5 28.5 83.3 60 75 100 100 100
# donors 45 21 5 6 9 3 2 5 4 3 0 0 1
The need is constant.
The gratification is instant.
Give blood. TM

Challenges to Reaching ARDP Goal
Donors--- ↑ rare donor submissions
Lack of antisera – Do a , Do b , Js a , Js b , Hy, Jo a , etc.
Lack of staff to screen donors
↑ time to manually screen
Cost of automation
Need for molecular characterization of donors
e.g., U, U var , hr B , hr S
The need is constant.
The gratification is instant.
Give blood. TM

Challenges to Reaching ARDP Goal
Patient requests---↓ unfilled requests
Few or no registered donors of requested
phenotype
Donors not reachable, ineligible, or deferred
Units not typed for lows—Js a , Kp a , etc.
Failure of donors to donate
Inadequate response to recruitment efforts
Numerous units/multiple requests for same
phenotype
Breakage of frozen units during shipping
Limitations to shipping frozen units on airlines
Need for molecular characterization of patients
(with antibodies to U, U var , hr B , hr S )
The need is constant.
The gratification is instant.
Give blood. TM

Impact of Molecular Testing
Donor submissions
↑ donor screening
↑ rare donor submissions
Patient requests
↓ patient requests through ARDP
↓ unfilled requests
↑ provision of liquid units
↑ provision of e variant units (e.g. hr B -)
The need is constant.
The gratification is instant.
Give blood. TM

Use of Molecular Testing
Screening
Use of high-throughput platforms
HEA TM BioArray BeadChip V1.0 and V1.2
Progenika BLOODchip ID
Gen-Probe LIFECODES RBC-R assay
Follow up
Sequencing by polymerase chain reaction (PCR)
The need is constant.
The gratification is instant.
Give blood. TM

HEA TM BioArray BeadChip V1.0 *
Blood Group
System
(~2008)
Predicted
Antigen
Blood Group
System
Rh C c E e Diego Di a Di b
Predicted
Antigen
Kell K k Colton Co a Co b
Kidd Jk a Jk b Dombrock Do a Do b Jo a
Hy
Duffy Fy a Fy b Fy x Landsteiner-
Weiner
Lw a Lw b
MNS M N S s Scianna Sc1 Sc2
Lutheran
Lu a Lu b
* Used at National Molecular Blood Group and Platelet Testing Laboratory
The need is constant.
The gratification is instant.
Give blood. TM

HEA TM BioArray BeadChip V1.2 *
Blood Group
System
The need is constant.
The gratification is instant.
Give blood. TM
(2009 to present)
Predicted
Antigen
Blood Group
System
Rh C c E e V VS Diego Di a Di b
Kell
Predicted
Antigen
K k Kp a Kp b Js a Colton Co a Co b
Js b
Kidd Jk a Jk b Dombrock Do a Do b Jo a
Duffy Fy a Fy b Fy x Landsteiner-
Weiner
Hy
Lw a Lw b
MNS M N S s U U var Scianna Sc1 Sc2
Lutheran
Lu a Lu b
* Used at National Molecular Blood Group and Platelet Testing Laboratory

↑ Donor Screening
# Donors Screened via HEA
Donor Screening via HEA TM BeadChip*
12000
10000
8000
6000
4000
2000
0
2008 2009 2010 Jul-11
* Data from National Molecular Blood Group and Platelet Testing Laboratory
The need is constant.
The gratification is instant.
Give blood. TM

Number submitted donors
↑ Rare Donor Submissions
7000
6000
5000
5097
6205
4000
3659
3000
2000
2153
1810 1786
2915
2201
1000
0
2004 2005 2006 2007 2008 2009 2010 Apr-11
The need is constant.
The gratification is instant.
Give blood. TM

# requests
↓ Patient Requests
1000
900
800
700
600
500
400
300
200
100
0
2003 2004 2005 2006 2007 2008 2009 2010
Total #
requests
649 668 693 806 795 951 916 918
The need is constant.
The gratification is instant.
Give blood. TM

% unfilled requests
↓ Unfilled ARDP Requests
14
12
10
8
6
4
2
0
2003 2004 2005 2006 2007 2008 2009 2010
# Unfilled 65 78 45 46 53 66 57 45
# Filled 558 565 590 691 704 833 814 839
Total # 649 668 693 806 795 951 916 918
The need is constant.
The gratification is instant.
Give blood. TM

↓ % Unfilled Requests—Highs
% unfilled requests
100
90
80
70
60
50
40
30
20
10
0
2005 2006 2007 2008 2009 2010
S-s-U-
Jo(a-)
Hy-
Js(b-)
Kp(b-)
Di(b-)
Lu(b-)
The need is constant.
The gratification is instant.
Give blood. TM

% requests filled with liquid units
↑ % Requests Filled with Liquid Units
100
90
80
70
60
50
40
30
20
10
0
2006 2007 2008 2009 2010 2011
# filled with liquids* 19 32 41 52 43 66
Total # filled requests* 60 63 61 72 70 75
* Data taken from January ARDP requests for each year
The need is constant.
The gratification is instant.
Give blood. TM

↑ Ability to Provide hr B - Units
Since 2007, HEA TM BioArray testing has been used
by National Molecular Blood Group and Platelet
Testing Laboratory to screen for hr B - donors
RHD and RHCE alleles of select donors and patient
samples are further characterized through RH
sequencing to predict specific hr B background
Characterized hr B - donors are entered into
database
Since 2008, database has been used by ARDP to
provide molecularly matched units for appropriate
patients
The need is constant.
The gratification is instant.
Give blood. TM

hr B - Characterization
Haplotype Markers VS V D by
Molecular
/Serology
C
Serology
ce S ce48C,733G,1006T VS+ V- D-/D- C-
(C)ce S (r’ S ) ce48C,733G,1006T VS+ V- Hybrid D/D- C+
(altered)
DIIIa-ce S ce48C,733G,1006T VS+ V- Partial D/D+ C-
ce733G ce733G VS+ V+ D-/D- C-
Dce733G ce733G VS+ V+ D+/D+ C-
ce48C ce48C VS- V- D-/D- C-
The need is constant.
The gratification is instant.
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hr B - Donors vs Requests
Since 2007, 141 hr B - donors have been characterized
and entered into database
Majority of donors entered since 2009
From 1/2009 to 4/2011, 84* ARDP requests for hr B -
units for 41 different patients
*7 requests—7 patients had 1 normal RHCE*ce allele or were E+
*5 requests—3 patients were not molecularly tested
*National Molecular Blood Group and Platelet Testing Laboratory
The need is constant.
The gratification is instant.
Give blood. TM

Common hr B - Genotypes of Patients and Donors*
Genotype
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# Patient
Requests
#
Donors
# Filled
Requests
# Unfilled
Requests
% Unfilled
Requests
(C)ce S /(C)ce S 9 21 7 2 22.2
ce S /(C)ce S 1 0 0 1 100
DIIIa-ce S /(C)ce S 34 6 30 4 12.9
Dce S /(C)ce S 2 4 2 0 0
Dce733G/(C)ce S 3 18 3 0 0
ce733G/(C)ce S 1 4 0 1 100
DIIIa-ce S /DIIIa-ce S 2 0 1 1 50
DIIIa-ce S /ce S 2 1 1 1 50
DIIIa-ce S/ Dce733G 2 15 1 1 50
ce733G/ ce733G 0 3 0 0 0
Dce733G/Dce733G 7 58 5 2 28.5
*National Molecular Blood Group and Platelet Testing Laboratory-12/2010

% Unfilled Requests for hr B -
% unfilled requests
35
30
25
20
15
10
5
0
2005 2006 2007 2008 2009 2010 Apr-11
# unfilled requests 3 1 2 4 9 4 1
# requests 10 19 25 18 30 33 13
The need is constant.
The gratification is instant.
Give blood. TM

Case Reports
2005
4 yr old with SCD / splenectomy
O pos, anti-Jk b , -hr B – want E- also
4 eligible donors; hr B - by serology
3 donated, 1 deferred
Patient and donor samples sent for RH
sequencing
The need is constant.
The gratification is instant.
Give blood. TM

Patient – Dce 733G /(C)ce S
2005
Donor Genotypes ABORh Other Ags Donors/Units
(C)ce S /(C)ce S O neg E- Jk(b-) 1—Florida
(C)ce S /(C)ce S O neg E- Jk(b-) 1--Wisconsin
Dce S /(C)ce S O pos E- Jk(b-) 1--Illinois
(C)ce S /ce 48C O neg E- Jk(b-) deferred
The need is constant.
The gratification is instant.
Give blood. TM

Patient – Dce 733G /(C)ce S
2010
Donor Genotypes Rh # Donors
(C)ce S /(C)ce S D neg 14
ce 733G /(C)ce S D neg 1
Dce 733G /(C)ce S D pos 17
Dce 733G /Dce 733G D pos 42
The need is constant.
The gratification is instant.
Give blood. TM

Patient– Baltimore
42 yr old woman with SCD
B pos with anti-C -E -K -Fy a -S -hr B
Functions at Hct of 10.5%
No donors in database
Between 2004 – 2008 a total of 10 units imported
from South African National Blood Service
The need is constant.
The gratification is instant.
Give blood. TM

Patient– Baltimore (cont.)
April 2008, ARDP received request for 2 units
Patient’s sample sent for molecular testing
DIIIa-ce S /Dce 733G
National Molecular Lab had characterized ~ 80
donors for hr B and/or hr S
The need is constant.
The gratification is instant.
Give blood. TM

Patient – DIIIa-ce S /Dce 733G
2008
Donor Genotypes ABO Other Ags Units
DIIIa-ce S /Dce 733G B K- Fy(a-) S+ 1 frozen
Dce 733G /Dce 733G A
Dce 48C,733G /Dce 733G B K- Fy(a-) S+ 1 frozen
DIIIa-ce S /ce B Not known No units
DIIIa-ce S /ce O K- Fy(a-) S- 1 frozen
Dce 733G /Dce 733G O Not known No units
Dce 733G /Dce 733G O Not known No units
DIIIa-ce 733G / DIIIa-ce 48C,733G O K- Fy(a-) S- 1 frozen
Dce S /Dce 733G O K- Fy(a-) S- 1 frozen
The need is constant.
The gratification is instant.
Give blood. TM

Patient – DIIIa-ce S /Dce 733G
2010
Donors Rh # donors
DIIIa-ce S /Dce 733G D pos 15
DIIIa-ce S / DIIIa-ce 733G D pos 2
DIIIa-ce S /D ce S D pos 1
DIIIa-ce S / ce S D pos 1
DIIIa-ce S /Dce 733G D pos 1
Dce 733G /Dce 733G D pos 42
ce 733G /ce 733G D neg 3
Dce S /Dce 733G D pos 2
The need is constant.
The gratification is instant.
Give blood. TM

Definition of Rare Blood
That blood component that is not available at
time of patient need
A precious commodity
Manage wisely!
The need is constant.
The gratification is instant.
Give blood. TM

Acknowledgments
•Sandra Nance
•Geralyn Meny
•Margaret Keller
•Lilian Castilho
•82 ARDP members
•ARDP staff at the ARC National
Reference Laboratory for Blood
Group Serology (NRLBGS)
•ARC National Molecular Blood
Group and Platelet Testing
Laboratory
flickingerc@usa.redcross.org
The need is constant.
The gratification is instant.
Give blood. TM