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Part II: International Rare Donor Programs

Journal of Blood Group Serology and Molecular Genetics


V o l u m e 32 , N u m b e r 2 , 2016
Immunohematology
Journal of Blood Group Serology and Molecular Genetics
Volume 32, Number 2, 2016
Part II: International Rare Donor Programs
CO N TEN TS

45 Introduction
S. Nance and C. Lomas-Francis

47 Review
Rare donor program in Italy
C. Paccapelo, F. Truglio, M.A. Villa, N. Revelli, M.C. Manera, E. Erba, and M. Marconi

49 Review
Rare donor program in Japan
Y. Tani

51 Review
Requests for red cells with rare blood types in the Netherlands
J.S. Luken, F. Danovic, M. De Haas, and M.M.W. Koopman

53 Review
The New Zealand rare donor program
D. Gounder

55 Review
Singapore rare donor program
R. Alcantara, J. Chay, and A.L. Ang

57 Review
Rare donor program at Western Province Blood Transfusion
Service in South Africa
R. Soeker
This issue of Immunohematology
is supported by a contribution from

Grifols Diagnostics Solutions, Inc.

Dedicated to advancement and education in


molecular and serologic immunohematology
59 Review
The Spanish program for rare blood donors
E. Muiz-Diaz, A. Castro, E. Flores, L. Larrea, F. Puente, M. Ayape, and
M.A. Prez-Vaquero

63 Review
Rare donor programs in Switzerland, Germany, and Austria
H. Hustinx, S. Lejon Crottet, E.A. Scharberg, and C. Weinstock

67 Review
The United Kingdom national rare donor panel
N.M. Thornton

71 Review
The American Rare Donor Program
C. Flickinger

75 C o m m e n tar y
Miracles do happen: meeting the challenges of providing rare
blood through the American Rare Donor Program
C. Flickinger

78 82 86 88
Announcements A dv ertisements Instructions Subscription
for Authors I n f o r m at i o n
Editor-in- Chief E d i t o r i a l B o ar d
Sandra Nance, MS, MT(ASCP)SBB
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Pomona, California Baltimore, Maryland
Managing Editor
Barbara J. Bryant, MD Thierry Peyrard, PharmD, PhD
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Wilmington, Delaware
Lilian M. Castilho, PhD Mark Popovsky, MD
Campinas, Brazil Braintree, Massachusetts
Te c h n i c a l E d i t o r s
Christine Lomas-Francis, MSc Martha R. Combs, MT(ASCP)SBB S. Gerald Sandler, MD
New York City, New York Durham, North Carolina Washington, District of Columbia

Joyce Poole, FIBMS Geoffrey Daniels, PhD Jill R. Storry, PhD


Bristol, United Kingdom Bristol, United Kingdom Lund, Sweden

Dawn M. Rumsey, ART(CSMLT) Anne F. Eder, MD David F. Stroncek, MD


Washington, District of Columbia Bethesda, Maryland
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David Moolten, MD Brenda J. Grossman, MD
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Baltimore, Maryland Geralyn M. Meny, MD Marion E. Reid, PhD, FIBMS
San Antonio, Texas New York City, New York
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Durham, North Carolina

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Margaret A. Keller, PhD
Philadelphia, Pennsylvania
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O n O ur C ov er

The International Society of Blood Transfusion Working Party on Rare Donors consists of
members from those countries around the world with rare donor programs. These members
work diligently to provide rare blood to their own patients in need as well as to those in other
countries when requested. Each members donors who are negative for high-prevalence antigens
are listed by phenotype on the World Health Organization International Rare Donor Panel.
Providing rare blood is a collaborative worldwide effort. The cover depicts the flags of those
member countries that contributed articles to Immunohematology.
Cy nthia Flickinger
Introduction
S. Nance and C. Lomas-Francis

The International Society of Blood Transfusion (ISBT) Part II


Working Party on Rare Donors was established in 1985 and Italy
is composed of experts in rare donor activities from many Japan
countries; its main focus is to ensure the availability of rare red Netherlands
blood cell (RBC) units for transfusion. Alloimmunization to New Zealand
RBC antigens may occur following transfusion or pregnancy. Singapore
Provision of blood may become challenging when a patient South Africa
has made an alloantibody to a high-prevalence antigen or Spain
made multiple antibodies to many more common antigens. To Switzerland, Germany, and Austria
have blood readily available for such situations requires access United Kingdom
to an inventory of extensively phenotyped blood as well as to United States
a database of rare donors who can be recruited for donation.
One way to accomplish this is to routinely screen donors to The authors were asked to provide information on several
search for rare blood types. A library of these rare donors is topics. First, they were asked to give details on the type of
maintained that contains information such as their antigenic rare donor program that exists in their country (national,
profile, demographic information for recruitment, and the RBC regional, or local) and to outline the history of their rare donor
units that they have donated (liquid and frozen). Managers program(s) (year started, and collaboration if regional or local
who are members of the World Health Organization (WHO) programs). Second, they were asked to provide data on the
International Rare Donor Panel (IRDP) can search the WHO number of active rare donors, the number of new rare donors
IRDP database and request rare blood from the members in added from 2012 to 2014, the number of rare units shipped
other countries who have the blood they need. Units are then (both domestically and internationally), and the number
shipped according to the specifications required by both the of requests for rare blood not filled. The authors were asked
shipping and receiving countries. to review patient cases where incompatible blood had to be
This issue of Immunohematology contains articles transfused because antigen-negative blood was not available
from many of the members of the ISBT Working Party on and to provide details on the outcome, prophylaxis given,
Rare Donors, detailing aspects of their countrys rare donor number of known cases, and other relevant details of these
program(s) and their approach to making units from rare cases that can be shared. The authors were also asked to share
donors available for transfusion. The submitted articles appear information about the incentives used in their country for
alphabetically according to country name in issues Volume 32, rare donor recruitment. The Rhnull phenotype is recognized as
Number 1, 2016, and Volume 32, Number 2, 2016, as Part I the rarest of the rare donors in the world; the members were
and Part II, respectively. asked to quantify the number of such donors and provide the
molecular background, if known.
Part I In the event that the readers of Immunohematology are
World Health Organization caring for patients with rare blood requirements, we hope
Belgium that this collection of articles will provide an insight into the
Brazil challenges of providing rare blood and allow our readers to
Canada be better informed and knowledgeable about international
China activities in the area of rare donor programs. The articles
Finland in this issue also serve to highlight the similarities and the
France differences between the programs and how they are managed
Iran in other countries.
Israel

I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016 45


Nance and Lomas-Francis

It is incredible and reassuring to observe the international


Sandra Nance, Immediate Past Chair (corresponding author), ISBT
support, cooperation, and collaborative efforts that occur Working Party on Rare Donors, American Red Cross, 700 Spring
across geographical and political boundaries when a patient is Garden Street, Philadelphia, PA 19123; Christine Lomas-Francis,
in need, especially when the need is for very rare blood. Chair, ISBT Working Party of Rare Donors, New York Blood Center,
We thank the authors of the articles for sharing their data Laboratory of Immunohematology and Genomics, Long Island, NY.
and experiences and the entire ISBT Working Party for their
commitment to making rare blood available whenever and
wherever it is needed.

Notice to Readers Attention:


State Blood Bank Meeting Organizers
All articles published, including communications and
book reviews, reflect the opinions of the authors and do If you are planning a state meeting and would like copies
not necessarily reflect the official policy of the American of Immunohematology for distribution, please send request,
Red Cross. 4 months in advance, to immuno@redcross.org.

46 I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016


Review

Rare donor program in Italy


C. Paccapelo, F. Truglio, M.A. Villa, N. Revelli, M.C. Manera, E. Erba, and M. Marconi

Although Italy lacks a national rare donor program, there kit performs multiple assays on one sample and analyzes
are several local and two regional rare donor programs in the 38 polymorphisms associated with 11 blood group systems
country. The first regional program, the Lombardy Rare Donor including RH, KEL, JK, FY, MNS, LU, DI, CO, DO, LW, and SC.
Programme (LORD-P), was established in 2005 in Lombardy, From 2005 to 2014, the program yielded 10,040 active
a region with an ethnically varied population of approximately donors who were rare for a combination of common antigens,
9.8 million inhabitants that includes 250,000 blood donors. 579 who were negative for high-prevalence antigens, and 48
In 2010, another rare donor program was established at the with a rare Rh phenotype. In 20122014, a total of 2492 new
Blood Transfusion Center of Ragusa Hospital in Sicily; this rare donors were added. Of these, 177 were rare for high-
program has typed 12,444 blood donors, of which 150 were prevalence antigens or Rh phenotype. In December 2014, the
negative for high-prevalence antigens [98 k, 26 Fy(ab), 3 LORD-P registry included the clinically relevant phenotypes
Co(a), 11 Lu(b), 1 Jo(a), 1 Di(b), 1 Js(b), 9 Yt(a)]. shown in Table 1.
LORD-P was established through the collaboration of
Table 1. Donors in rare donor program in Italy (20052014)
15 regional blood transfusion departments and with the
Antigen/phenotype Number of donors
support of a regional government grant. During 2005 to
Yt(a) 196
2014, the Lombardy Region supported LORD-P with 1.3
Fy(ab) 140
million per year. The LORD-P and blood bank of fresh and
k 129
frozen rare red blood cell (RBC) units were established at the
Co(ab+) 56
Blood Transfusion Centre, Foundation Ca' Granda Ospedale
Lu(b) 44
Maggiore Policlinico, in Milan under the coordination of the
CCdee (rr) 31
Immunohematology Reference Laboratory (IRL), which has
ccdEE (rr) 9
been accredited as an IRL by the AABB since 2003. Each of
CCDEE (R zR z) 6
the 15 regional blood transfusion departments selects blood Kp(b) 5
donors aged 1855 years (including Caucasians and ethnic Fy(ab) Js(b) 4
minorities) with a history of two or more blood donations and PP1Pk 2
sends a small blood sample for extensive typing to the IRL. D 2
From 2005 to June 2009, an automated, high-throughput Js(b) 1
system (Galileo, Immucor, Norcross, GA) was used for the Co(ab+) Yt(a) 1
serological typing of groups A and O blood donors, selected by GE:2 1
Rh phenotype (CCDee [R1R1], ccdee [rr], ccDEE [R2R2], ccDee Total 627
[R0R0]) and being negative for K or k. The panel tested for Fya,
Fyb; Jka, Jkb; S, s; Coa; Jsb; Ge2; Lub; Kpb; PP1Pk; U; Vel; and Yta. Although originally established to meet the needs of
Until December 2006, antigen-negative status was confirmed patients treated in Lombardy, the LORD-P registry and
serologically using different antisera by Galileo or by manual blood bank of frozen RBC units has contributed to resolving
tube testing. Beginning in January 2007, all confirmatory planned and urgent transfusion needs of complex immunized
typing was performed by molecular methods using a local transfusion candidates throughout the country.
procedure incorporating Luminex technology (Luminex Corp., In 20122014, a total of 1058 requests for rare blood units
Austin, TX) or by commercial polymerase chain reactions with were referred to LORD-P registry and 1595 rare units were
sequence-specific primers (Inno-Train Diagnostik, Kronberg, issued. Of these, 450 were rare for high-prevalence antigens or
Taunus, Germany). Starting in June 2009, a high-throughput rare for Rh phenotype, as shown in Table 2.
genotyping method based on DNA microarray technology, During 20122014, all requests for compatible units were
the HEA BeadChip kit (BioArray Solutions, Immucor), was filled, with the exception of one request for Gy(a) units for
used to increase the number of typed RBC alleles. The HEA delivery in a pregnant woman with anti-Gya. A 33-year-old

I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016 47


C. Paccapelo et al.

Table 2. Rare units issued in 20122014 Rhnull Donors


Antigen/phenotype Number of units
Yt(a) 153 As reported in the literature,1,2 the Rhnull phenotype is
k 122 extremely rare and is associated with two distinct molecular
Fy(ab) 74 backgrounds: the amorph type results from inactivating
Lu(b) 74 mutations in RHCE and a deletion of RHD, whereas the regular
CCdee (rr) 13 type results from homozygosity for inactivating mutations in
CCDEE (R zR z) 5 RHAG. According to the results of a survey by the International
Js(b) 4 Society of Blood Transfusion Rare Donor Working Party in
ccdEE (rr) 3 Amsterdam in 2013, no Rhnull donor has been identified in
U 2 Italy.
Total 450

Acknowledgments
woman at 25 weeks gestation was referred to our hospital
because her antibody screen was positive by an indirect We thank Simone Travali of the Immunohematology and
antiglobulin test (IAT) with all cells tested. We detected anti- Transfusion Medicine Service of Ragusa for sharing data on
Gya with a very low titer (1) by the IAT. The prevalence of their rare donor program.
Gy(a) is known to be extremely rare, and only four donors
were available in the International Rare Donor Panel. At 40 References
weeks gestation, a baby was delivered by caesarean section,
1. Daniels G. Human blood groups. 3rd ed. Hoboken, NJ: Wiley-
but no units were available. For this reason, IgG prophylaxis Blackwell, 2013.
was recommended, but during the delivery, RBC units were 2. Reid ME, Lomas-Francis C, Olsson M. The blood group antigen
not necessary. The infant suffered neither from anemia nor factsbook. 3rd ed. Cambridge, MA: Academic Press, 2012.
from severe jaundice.
Cinzia Paccapelo, ScD (corresponding author), Senior Assistant
Biologist, Immunohematology Reference Laboratory Transfusion
Incompatible Transfusion Cases
Centre, IRCCS Foundation C Granda Ospedale Policlinico, Milan,
Italy, c.paccapelo@policlinico.mi.it; Francesca Truglio, MLT, Senior
No reports of acute or delayed hemolytic transfusion Technician; Maria Antonietta Villa, ScD, Technical Supervisor;
reactions were received by the IRL after the transfusion Nicoletta Revelli, ScD, Technical Supervisor; Maria Cristina Manera,
of shipped rare RBC units, although we are aware of the ScD, Senior Assistant Biologist; Elisa Erba, MLT, Senior Technician;
possibility of inaccurate or incomplete reporting of adverse Maurizio Marconi, MD, Medical Director, Immunohematology
Reference Laboratory Transfusion Centre, IRCCS Foundation C
events and transfusion reactions.
Granda Ospedale Policlinico, Milan, Italy.

Incentives for Rare Donors

Despite the increase in blood usage and the critical


seasonal blood shortages, the national blood service is based
on voluntary non-remunerated blood donations. In fact,
donors do not receive any cash incentives but may be given
the day off from work on the day of donation. Furthermore,
donors may be enrolled in preventive medicine programs
offered by the blood center.

48 I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016


Review

Rare donor program in Japan


Y. Tani

National Program in Japan Table 1. Number of active rare donors in Japan as of March 2015
Category I
The national Japanese rare blood program was established Phenotype D+ D Phenotype D+ D
in 1987 by the Japanese Red Cross (JRC). The JRC defined Oh (Bombay) 3 0 McLeod 18 0
rare blood as one that occurs at a prevalence of 1:100 or MkMk 1 0 I 20 0
less. The JRC classifies rare blood types into two categories En(a) 2 0 Ge 11 0
according to their prevalence: those in category I are found Mi.V/Mi.V 4 0 Lan 19 0
in less than 1:10,000 individuals, and those in category II are Nsat/Nsat 2 0 Gy(a) 6 0
found in between 1:100 and 1:10,000 individuals. Although SsU 1 1 Ok(a) 19 0

the prevalence of the D blood type is also low (1:200 in P k


3 0 JMH 12 0

Japan), it is not considered rare, as we have no problem finding Rhnull 4 para-Bombay 78 0

compatible blood because every donor is routinely typed for Rhmod 6 p 25 0


Kp(ab) 2 0 D 107
D. Phenotypes in category I are Mk/Mk, En(a), Mi.V/Mi.V,
k 9 0 In(Lu) 124 2
Nsat/Nsat, S/s/U, p, Pk, Rhnull, Rhmod, D, Dc, R zR z,
K:14 2 0 K0 106 2
r yr y, rr, Lu(ab), In(Lu), K0, Kp(a+b), Kp(ab), k, K mod,
Fy(ab) 8 1 Jk(ab) 66 1
K14, K18, KYOR, Fy(ab), Jk(ab), Gy(a), LW(ab),
Dr(a) 1 0
Oh (Bombay), para-Bombay, Kx (McLeod), GE:2,3, IFC,
IFC 1 0
UMC, Dr(a), Ok(a) , JMH, I, Lan, Er(a), and Emm,
and those in category II are s, Fy(ab+), Di(a+b), Jr(a), and Category I Category II
Do(a+b). Rare phenotype D Rare phenotype D+
Donors are registered when their blood type is identified Fy(a+b) 491 Fy(a+b) 3,416
as rare and they are requested to donate their blood if needed. Di(a+b) 102 Di(a+b) 2,785
We usually keep blood in category I as frozen units. Blood in Jr(a) 44 Jr(a) 2,323
category II is usually supplied to hospitals as fresh units. s 113 s 357

Number of Active Rare Donors


Table 2. Rare donor entries in Japan from 2012 to 2014
The JRC screens for rare cells on an automated analyzer Phenotype Number of donors
(PK7300, Beckman Coulter K.K., Tokyo, Japan) using Lu(ab) or In(Lu) 29
monoclonal antibodies, most of which were established by the K0 11
JRC. The following monoclonal antibodies are routinely used D 7
for screening: anti-Rh17, anti-Jra, anti-K2 or anti-K14, anti- Lan 4
EnaFR, anti-Ge, anti-Lan, anti-CD44, anti-Dib, anti-Oka, and p 3
anti-IFC. M /Mk k
2
Table 1 lists the number of active rare donors. Phenotypes Jk(ab) 2
that are the most difficult to find in Japan are MkMk, En(a), para-Bombay 2
U, p, Pk, Rhnull, McLeod, Ge, and Lan. Table 2 shows the 65 N /Nsat sat
1
new rare donors added from 2012 to 2014. Pk 1
Gy(a) 1
Fy(ab) 1
I 1
Total 65

I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016 49


Y. Tani

Rare Units Shipped in 20122013 Incompatible Transfusion Cases


Twelve cases (six cases of anti-Jra, one anti-Emm,1 one
In Japan, one unit corresponds to 200 mL whole blood anti-Kpc, 1 anti-Ge, one anti-Gya, one anti-JMH, and one anti-
drawn from a donor. In 20122013, the JRC shipped 3897 AnWj) of incompatible transfusions were reported between
units of rare blood domestically and 21 units internationally 2012 and 2014. According to the reports, no prophylaxis was
(Table 3). The international shipments included 7 units of given in these 12 cases. Irregular antibodies could not be
Lan (red cell concentratesleukocytes reduced [RCC-LR]), identified in the case of anti-Emm nor detected in the case of
4 units of p (RCC-LR), and 2 units of D (RCC-LR) to anti-Kpc in pre-transfusion tests. These antibodies led to acute
Australia; 4 units of K0 (frozen thawed red cellsleukocytes hemolytic transfusion reactions; the other antibodies did not.
reduced [FTRC-LR]) to the UK; and 4 units of Rhnull (FTRC-
LR) to Norway. Incentives for Rare Donors

Table 3. Rare units provided domestically and internationally The JRC has no incentives for rare donors.
through the Japanese Red Cross in 20122013
Domestic International Rhnull Donors
Phenotype Number of units Number of units Country
Jr(a) 2113 0 NA Rhnull donors are recognized as the most rare of the rare
Fy(ab+) 1255 0 NA donors in the world. Currently, we have four group A, Rhnull
Di(a+b) 330 0 NA donors; their molecular backgrounds have not been examined.
D 90 2 Australia
p 58 4 Australia References
K0 12 4 UK
s 14 0 NA 1. Takahashi J, Date E, Kusumi T, et al. The first example of an
acute hemolytic transfusion reaction due to anti-Emm and
Lan 3 7 Australia the first Japanese proband [Abstract]. Vox Sang 2013;105
I 8 0 NA (Suppl 2):21.
Jk(ab) 4 0 NA
In(Lu) 4 0 NA Yoshihiko Tani, MD, PhD, Vice-Director, Japanese Red Cross Kinki
para-Bombay 4 0 NA Block Blood Center, 7-5-17, Asagi Saito, Ibaraki, Osaka, 567-0085,
Rhnull 0 4 Norway Japan, y-tani@kk.bbc.jrc.or.jp.
Fy(ab) 2 0 NA
Total 3897 21
NA = not applicable.

Number of Requests not Filled


All cases for requested rare units of blood were filled in
20122014.

50 I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016


Review

Requests for red cells with rare blood types in


the Netherlands
J.S. Luken, F. Danovic, M. De Haas, and M.M.W. Koopman

In the Netherlands (16.9 million inhabitants), blood units Rare Phenotypes


are nationally provided by Sanquin Blood Supply, which Multiple Antibodies: 245
includes a nationally organized rare donor program. Since Fy(ab): 47
the 1970s, donated red blood cell (RBC) units with rare blood Lu(b): 40
types have been frozen and stored. This began as part of the Vel: 26
European Bank of Frozen Blood of the Council of Europe, with k: 25
contributions from several European countries. In 2006, this Yt(a): 23
became the Sanquin Bank of Frozen Blood (SBFB). In early Kp(b): 20
2015, 1294 units of frozen blood with rare phenotypes were rr: 14
stored at the SBFB. PP1Pk: 14
Sanquin Blood Bank uses a cohort of 380,000 regular, Unidentified HPA: 13 autologous

repeat blood donors and approximately 900 active rare donors, rr: 12

who are negative for a high-prevalence antigen. All donors Ge:2,3: 11

donate on a voluntary basis and no incentives are given to rare U: 9


Lu(ab): 8
donors.
Jk(ab): 6
We have different methods to enlarge the rare donor
R o: 5
cohort. First, patients who have been identified with RBC
Co(a): 4
alloantibodies and found to be negative for a high-prevalence
Jr(a): 2
antigen are asked to become rare donors. Second, family
Di(b): 2
members of these patients are tested and asked to become
At(a): 2
donors if they are also negative for the antigen. Third, Sanquin
H: 2
Blood Bank types donors for different RBC antigens such
K 0: 1
as k, Lub, and Kpb on a regular basis. In general, we add
Lan: 1
approximately 15 new rare donors to our database each year.
10 20 30 40 50 60 70
When rare blood is needed, we prefer the use of a fresh unit
from one of the rare donors rather than a deglycerolized unit. Issued RBCs (fresh and deglycerolized)
Although the rare donor cohort consists of several rare
Fig. 1. Overview of the phenotypes of issued units of rare red blood
blood types, and requests in general can be filled, there is a cells (RBCs) in the Netherlands, both fresh and deglycerolized,
shortage of rare donors with non-Caucasian phenotypes between 2008 and 2014. HPA = antibody to high-prevalence
antigen.
such as U or Js(b). Currently, we are evaluating whether
we should make more effort to find non-Caucasian donors to
extend the rare donor population. Furthermore, extremely rare during this time period were for a few patients with weakly
donors such as Rhnull or K0 donors are lacking in our cohort. reactive (<2+) anti-Yta because Rh-matched, Yt(a) units were
not available and no transfusion reactions were expected. In
Issued Units these cases, no additional measures were taken.
From 2008 to 2014, a total of 434 units of fresh RBCs were
Rare RBC units, either deglycerolized or fresh, issued issued. Of these units, 429 (99%) originated from Dutch donors.
between January 2008 and December 2014 for patients in In the same period, 98 units of RBCs with rare phenotypes
the Netherlands are shown in Figure 1. All requests during were thawed and deglycerolized through the SBFB. Of these
this period were filled. The only incompatible units transfused deglycerolized units, 63 (64%) originated from Dutch donors,

I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016 51


J.S. Luken et al.

and the other 35 units (36%) were received from blood banks
outside the Netherlands. The 434 units of fresh RBCs were fresh RBCs

issued for 137 patients and the 98 units of deglycerolized deglycerolized RBCs

RBCs were issued for 40 patients. Of the patients who received


fresh RBCs, 118 (86%) patients were female, of whom 57

Number of units
were pregnant. A total of 100 (23%) units were issued during
delivery. For the units of deglycerolized RBCs, 26 (70%) were
for female patients of whom 10 were pregnant; 16 units (16%)
were deglycerolized for use during delivery.
In the group of patients who received fresh RBCs, 28
patients (20%) received autologous units, as compared with 16
(40%) patients who received deglycerolized RBCs.

Conclusions
Fig. 2. Overview of the total amount of fresh and deglycerolized red
blood cell (RBC) units issued in the Netherlands between 2008
Thanks to the national rare donor program, a steep and 2014.
increase in the issue of fresh RBC units and a decrease in the
issue of deglycerolized RBC units have been observed in the
last 7 years (Fig. 2). Of the fresh units of RBCs issued, 100 were
ordered for female patients during delivery as compared with Jessie S. Luken, MD (corresponding author), Consultant,
10 units of deglycerolized RBCs. The relatively high proportion Transfusion Medicine, Sanquin Blood Supply, Department of
of units of fresh RBCs ordered for pregnant patients during Transfusion Medicine and Sanquin Diagnostics, Department of
Immunohematology Diagnostics, Plesmanlaan, 125, 1066 CX
delivery can be explained by the fact that it is easier and less
Amsterdam, the Netherlands, j.luken@sanquin.nl; Fikreta Danovic,
costly to order units of fresh RBCs as a preventive measure MD, Consultant, Transfusion Medicine, Sanquin Blood Supply,
than units of deglycerolized RBCs, ensuring a substantial Department of Transfusion Medicine; Masja de Haas, MD, PhD,
contribution to optimize a patients safety. Sanquin Diagnostics, Laboratory Director of the Department of
The overall contribution of autologous units is low, Immunohematology Diagnostics; Rianne (M.M.W.) Koopman, MD,
especially for fresh RBCs. PhD, Internist, Consultant, Transfusion Medicine, Sanquin Blood
Supply, Department of Transfusion Medicine, Amsterdam, the
Because of the national rare donor program, almost
Netherlands.
all donors of fresh RBCs and a majority of the donors of the
deglycerolized RBCs are of Dutch origin, thereby providing
a self-sufficient blood supply. International collaboration,
however, remains very important, especially when there is a
need to find compatible blood for patients with non-Caucasian
phenotypes.

52 I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016


Review

The New Zealand rare donor program


D. Gounder

The New Zealand rare donor program was formally Report of incompatible blood transfusions
established in 1986the same year that the International
Society of Blood Transfusion (ISBT) Working Party on Rare We have had one case of delayed hemolytic transfusion
Blood Donors was formed.1 Prior to this (since the mid-1970s), reaction in a Polynesian patient who received an emergency
frozen blood units with rare blood types were maintained. transfusion of 6 units of Jk(a+b+) blood for bleeding from
These units would have been mainly for national use. More a gunshot injury. He was subsequently identified to have
recently, the rare donor inventory of active donors has been developed anti-Jk3 from a previous transfusion. He was
updated to record the extended phenotype of individual changed to Jk(ab) blood. Two days later, there was laboratory
donors. evidence of a delayed hemolytic transfusion reaction with a
mild drop in the hemoglobin level. The patient was discharged
Important aspects of the program without any long-term clinical consequence.

Presently, we have 69 active donors, of whom 34 are Rare donor incentives


Jk(ab) (Table 1). Between 2012 and 2014, 15 new donors
were addedthe majority being Jk(ab). In the same period The major focus for New Zealand has been the Jk(ab)
we shipped 17 Jk(ab) liquid units to Australia, most of phenotype. More recently, the availability and supply of
which were needed for a single patient. We actively manage our Jk(ab) blood has been a challenge for us with the need to
frozen red cell inventory to ensure that we can maintain target ship blood to Australia from time to time. The majority of
numbers for the rare types considered important. Because we our Jk(ab) donors are of Polynesian descent. We continue
still have units in storage that do not meet our current donor to experience poor retention of these donors. There is little
accreditation requirements, it has become necessary that these knowledge of local Polynesian and Maori blood donation
units be replaced. Although challenging at times, we continue attitudes and behaviors. A more targeted recruitment and
to maintain an ability to fulfil Jk(ab) requests from within retention program has been suggested, probably with focus
New Zealand and abroad. We have not identified any Rhnull on community responsibility systems. This program may be
donors in particular in New Zealand. better suited to Polynesian and Maori communities.2

Table 1. Active rare donors in New Zealand


References
Phenotype Number of donors
1. Woodfield G, Poole J, Nance ST, Daniels G. A review of the
Jk(ab) 34
ISBT rare blood donor program. Immunohematology 2004;20:
k 29 24448.
Lu(b) 3 2. Glynn SA, Kleinman SH, Schreiber GB, et al. Motivations to
rr 2 donate blood: demographic comparisons. Transfusion 2002;
42:21625.
(Oh ) Bombay 2
Vel 1
Co(a) 1

I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016 53


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54 I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016


Review

Singapore rare donor program


R. Alcantara, J. Chay, and A.L. Ang

In Singapore, rare blood donors are those whose red is possible. If not, we screen the patients immediate family
blood cells (RBCs) lack a high-prevalence antigen or lack a members (siblings and parents) to look for the rare blood
combination of common antigens that can only be found in 1 phenotype. We apply similar stringent selection criteria as
in 1000 or fewer blood donors (Table 1). for any other blood donor before accepting blood donations
The Health Sciences Authoritys Blood Services Group from these family members. In 2014, we had to supply blood
(BSG) is the national blood service in Singapore. The BSG has for a neonate with hemolytic disease of the fetus and newborn
been maintaining a registry of donors with rare blood types caused by anti-Hr0. Because of the urgency of the transfusion
since 2004. RBC units from these donors are cryopreserved requirement and ABO incompatibility with the mother, we
using the high-concentration (40%) glycerol method and a screened the mothers siblings and found one of them to be
slow freezing rate. Frozen rare donor RBC units are stored at negative for Hr0; this individual became a regular voluntary
65C or lower in mechanical freezers and are kept for up to blood donor.
10 years. Because knowledge of the distribution of blood groups
With more patients receiving blood transfusions for present in our donor population can help in the identification
complex surgeries and undergoing aggressive treatments of rare phenotypes, we are presently revising our screening
for hematological diseases (chemotherapy, bone marrow strategies using our local antigen prevalence data to make the
transplant, etc.) in Singapore, our national Red Cell Serology screening process for rare blood types more efficient. We are
Reference Laboratory started to notice an increase in the num- also in discussion with the Singapore Red Cross to design a
ber of multiple RBC alloantibodies in transfusion recipients program for maintaining our existing rare blood donors and
and the appearance of RBC antibodies not previously seen in recruiting new blood donors. Under a unique partnership with
Singapore (e.g., anti-k). BSG, the Singapore Red Cross is responsible for the national
Since 2011, BSG has been maintaining a regular inventory blood donor recruitment and retention program.
of non-cryopreserved phenotyped blood to ensure that BSG follows a policy of voluntary non-remunerated blood
antigen-negative RBC units are readily available for patients donation, and rare blood donors are managed in the same way
because the thawing and deglycerolization process of frozen as the rest of the blood donors, with no material rewards or
blood units takes several hours. This inventory includes Fy(a), incentives. However, they are informed that they will be given
Fy(b), Jk(a), Jk(b), S, and s RBC units, as well as units priority access to the rare blood inventory in the event that
with multiple common antigennegative combinations such they need blood themselves.
as R1R1 Fy(a) or Fy(b); R2R2 s; or R1R1 Jk(a) or Jk(b), Currently, we have 37 active donors that meet our
and s. definition of a rare blood donor, and we have included them
The Singapore Rare Donor Program aims to meet the in our rare blood donor registry (Table 1). From these donors,
rare blood requirements of patients in Singapore through we were able to collect 43 RBC units, which are currently in
appropriate targeted screening among the regular voluntary our frozen inventory. Between 2012 and 2014, there were three
blood donors. An example of this initiative was the mass cases (liver transplant, lung resection, and placenta previa) of
screening of blood donors in 2013 using the urea lysis test patients in Singapore requiring rare blood, and these patients
on the Olympus PK7300 as a rapid screening for Jk(ab) were fully supported. Besides screening for donors of rare
donors after having to supply blood for a surgical patient with blood required locally, we also hope to find some donors of
alloantibody to Jk3. We were able to identify an additional 10 other rare blood types encountered in other Asian countries
donors, all confirmed to be Jk(ab) by serology. Our study [Rhnull, Di(b), etc.]. We have not transfused incompatible
also showed that the prevalence of Jk(ab) phenotype was 1 blood to recipients requiring antigen-negative RBC units.
in 3600 in the Singapore donor population. Rare donor units collected and kept in frozen inventory
If rare blood cannot be found among our donor population, starting from 2006 follow the International Society of Blood
we first discuss with the clinician if autologous transfusion Transfusion (ISBT) 128 standard for labeling, which is the

I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016 55


R. Alcantara et al.

Table 1. Donor and cryopreserved unit information for blood types global standard for the identification, labeling, and information
considered rare in Singapore (in 1:1000 donors) as of 2015.
transfer of human blood, cell, tissue, and organ products across
High-prevalence antigen-negative international borders and disparate health care systems. This
Number of system will facilitate international shipping of blood products
Number of cryopreserved
Phenotype donors RBC units available in Singapore to other countries if there is a request for
Jk(ab) 32 36 rare blood units, although BSG has not imported or received a
H (Oh) 4 5
request from other countries or blood centers to provide rare
donor units in recent years.
Hr 0 (D) 1 2

Multiple antigen-negative combinations Acknowledgments


R1R1, Jk(a) or Jk(b), Fy(a) or Fy(b), and s 0 0
R2R2, Jk(a) or Jk(b), Fy(a) or Fy(b), and s 0 0 The authors would like to express their special thanks to
R2R2, Fy(a), s 0 0 Mr. Marvin Millana, Ms. Rosalind Loo, and Ms. Clara Lim for
rr, Jk(a) or Jk(b), Fy(a) or Fy(b), and s 0 0 their valuable help in the Singapore Rare Donor Program.
rr, Fy(a), or s 0 0

Ramir Alcantara, MD (corresponding author), Registrar, Blood


Services Group, Health Sciences Authority, 11 Outram Road,
Singapore, 169078, ramirmd@yahoo.com; Jason Chay, MD, Blood
Services Group, Health Sciences Authority, Singapore; Ai Leen Ang,
MD, FRCPath, Consultant, Blood Services Group, Health Sciences
Authority and Department of Hematology, Singapore General
Hospital, Singapore.

56 I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016


Review

Rare donor program at Western Province


Blood Transfusion Service in South Africa
R. Soeker

The rare donor program at Western Province Blood Table 1. Summary of rare donors at Western Province Blood
Transfusion Service in South Africa as of November 2015
Transfusion Service (WPBTS) is a regional rare donor
program established in 1986. In collaboration with the South Phenotype ABO group Number of donors Donation status

African National Blood Service (SANBS), rare donors are C E K Fy(ab) Jk(b) O 76 Active
S (GATA mutation)
phlebotomized for use of their collected units both locally
hrB (RH:31) O 10 Active
and internationally. Units are stored frozen at a single storage
k O 10 Active
facility within SANBS in Durban. SANBS manages the frozen
C E K Fy(ab) Jk(b) O 5 Active
inventoried units. Rare units in the liquid state are managed s (GATA mutation)
by their respective centers. The International Blood Group U O 4 Active
Reference Laboratory liaises with SANBS; WPBTS receives
B 1 Not active
international requests from SANBS and ships the liquid unit
Hr (RH:34)
B
O 4 (3 are sisters) Active
to the client when needed if it is more practical.
hrS (RH:19) O 3 Active
The number of active rare donors at WPBTS is 119. There
Jo(a) O 2 Active
were 71 new rare donors added between 2012 and 2014. These
Oh (Bombay) Oh 1 Active
consisted of donors lacking high-prevalence antigens. Most of
the active rare donors have phenotypes with Fy(ab), s, and Rhnull O 1 Active

Jk(b) combinations. These donors were identified through A 1 Active

screening efforts at WPBTS. Gerbich null O 1 Not active


A 1 Not active
Shipments Lu(b) O 1 Active
Js(b) O 1 Active
When SANBS has insufficient stock or a liquid blood unit
is required, the WPBTS is approached to fulfill the request. household provisions. They are not used as incentives and are
WPBTS has shipped Rhnull units to Ireland, Canada, and provided to donors that are seen to be underprivileged.
Australia when a liquid unit was requested. At WPBTS, we do WPBTS has two Rhnull donors. The genetic background
not normally ship frozen rare units internationally, as our rare of one donor is GA-154_157delCCTCins GA; the genetic
donor units are stored frozen within SANBS (as noted earlier) background of the other is not known.
for international use.
In the timeframe of 20122014, there were 46 rare units Transfusion Reactions
shipped domestically and 9 shipped internationally.
The following describes a case of an HrS patient with anti-
Incentives for Rare Donors HrS who received 2 emergency units in 2012. No transfusion
reaction was observed or reported.
Our rare donors (Table 1) are invited to the annual Donor In January 2012, a pregnant woman from Nigeria
Long Service Awards evening, where they are honored for their delivered her baby in Cape Town. At the time of her delivery,
contribution. They are phlebotomized at their place of work or she received 2 units of group O, D random emergency blood.
home when required to do so, i.e., in cases of emergency when No pre-transfusion immunohematologic tests were performed,
they are unable to attend one of our fixed site or mobile clinics as this was an emergency situation. Samples were then sent for
because of their time constraints. Carepacks are provided antibody screens and, because no further blood was required,
for impoverished donors. These carepacks consist of general the patient was discharged after a vaginal delivery and sent

I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016 57


R. Soeker

home with her baby. She was readmitted a few days later, as during the family study). One year later, the patient enrolled
she had a massive bleed and was anemic. Samples were then as a rare blood donor. She has donated for two local patients.
sent with a request for crossmatched blood. The results of Immigration issues for these donors are dynamic, and this
the antibody screens were as follows: antibody screens were causes them to be difficult to locate. In addition, regulations for
positive in enzyme and in antihuman globulin (AHG) media donation after travel to malarial zones postpone donation for 3
utilizing an automated gel test system (Serascan Diana 3 and years; the former patient visits her home at least every 2 years,
Serascan Diana 3P, Grifols, Barcelona, Spain). The test results making donation nearly impossible. Her brother does not visit
demonstrated anti-E reacting 3+ and 4+, respectively. Our home very often, but other factors cause him to be periodically
in-house WPBTS panel (utilizing the tube method) showed deferred from donating for 6-month increments.
antibodies with Rh specificity (yielding results 1+ and 2+ Rare donors are important to keep in the system, and
macro at room temperature, 37C, and AHG readings). the immunohematology laboratories in South Africa work
Anti-HrS was suspected and confirmed by the SANBS intensely to keep track of their rare donors.
Reference Laboratory, and the patient was typed as HrS. No
transfusion reaction was noted during or after the infusion of Ruwayda Soeker, BA, Reference Laboratory Supervisor, Western
Province Blood Transfusion Service, Old Mill Rd., Ndabeni,
the emergency blood. After the identification of the antibody,
Pinelands, 7405, South Africa, ruwayda@wpbts.org.za.
the patient received compatible blood1 unit from the SANBS
Rare Donor File and 1 unit later from her brother (identified

58 I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016


Review

The Spanish program for rare blood donors


E. Muiz-Diaz, A. Castro, E. Flores, L. Larrea, F. Puente, M. Ayape, and M.A. Prez-Vaquero*

The Spanish program for rare blood donors was created and suggested that the cooperative group should be constituted
in 2005. Before that year, no official program existed and no as a Working Party of SETS.
government measure had been taken to create a program A year later, the national stock of cryopreserved units with
for providing rare blood for patients in need. To better rare blood types (consisting of 658 units) was published for
understand the origin, history, and outcome of our program, the first time. Since then, this information has been updated
it is necessary to understand how Spain is organized from a and published every year in the SETS journal and on the
political and administrative point of view. Spain is divided into Web site of our Society. The list and the phenotype profile of
17 autonomous regions, each with its own government and the 766 cryopreserved rare units of blood currently available
health care, making health care in Spain highly decentralized. are shown in Table 1. In addition, the program has a list of
The regional governments are in charge of managing their 900 rare blood donors willing to give blood in emergency
own health services and work as competent authorities as cases. This list needs to be upgraded, however, to distinguish
part of the National Network of Blood Establishments and between two types of donors: (1) donors willing to give blood
Hospital Transfusion Services. The Ministry of Health, in after being informed about their rare phenotype and (2) donors
Madrid, coordinates the functions of the whole health care with a rare phenotype but who have not yet been informed. In
structure and works as the competent authority for many practice, only the first group of donors should be included in
responsibilities, including managing the relationship with our reports.
the European Union. About 2 million blood components were To make the service more workable and more uniform, a
transfused in Spain in 2014. All these units were collected, protocol for requesting rare blood units was established. This
processed, and distributed by 24 blood transfusion centers protocol includes the Requesting Form and the Receiving
(BTCs) and were transfused at 400 hospitals throughout the Form; both forms are available from the Web site of our Society.
country. The Requesting Form consists of two parts: one part concerns
For several years, four BTCs, each from a different region, the details of the requesting center and the other part deals
had been working on the collection and the cryopreservation with the details of the patient (e.g., phenotype of the RBCs
of red blood cells (RBCs) with rare phenotypes (Catalonia, requested, number of units, and the preferred mode of units
Galicia, Madrid, and Valencia), and a fifth center (Navarra) requested [cryopreserved, thawed, or fresh]). The Receiving
participated by providing a list of donors with rare phenotypes. Form, inspired by the form originally designed by the Working
All this work was undertaken on the initiative of these Party on Rare Donors of the International Society of Blood
BTCs, given the absence of a national policy concerning the Transfusion (ISBT), also consists of two parts: one concerns
collection, maintenance, and provision of rare blood. At that the shipping center and the other concerns the patient (e.g.,
time, each center knew what units it had at its disposal, but whether or not the units arrived in perfect condition [state
this information was not available to the public. No one in the of the bag, temperature, etc.]). Moreover, to provide a more
country knew the total number of cryopreserved units, the efficient service, each BTC is responsible for the rare RBC
total number of rare blood donors, or the antigenic profiles of units requested from a certain number of autonomous regions.
these units and donors. Finally, at the end of 2005, the Spanish The BTC of reference may request a sample from the hospital
program for rare blood donors was established, consisting whenever it considers this to be necessary. If the units are
of the five BTCs involved in the management of rare blood not available in Spain, the BTC of Catalonia is responsible for
phenotypes. Additionally, the group requested the support of obtaining the units from the International Rare Donor Panel
the Spanish Society of Blood Transfusion (SETS), who agreed (IRDP) in Bristol, United Kingdom. Our rare units of blood

*All authors are members of the Spanish Working Party on Rare Donors. Dr. E. Muiz-Diaz is also a member of the International Society of
Blood Transfusion Working Party for Rare Donors.

I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016 59


E. Muiz-Diaz et al.

Table 1. Inventory of cryopreserved units of rare blood in the Spanish program for rare blood donors, 2015
Phenotype A+ A O+ O AB+ AB B+ B Total
k 25 18 86 60 0 0 0 0 189
Lu(a+b) 12 2 38 43 1 0 0 0 96
Fy(ab) 8 1 32 38 0 0 0 0 79
PP1P k
17 0 32 5 1 0 19 0 74
Kp(a+b) 12 0 15 38 0 1 0 3 69
Vel 4 10 21 15 1 0 0 0 51
Co(a) 5 0 25 4 0 0 0 0 34
Yt(a) 6 3 17 6 0 0 0 0 32
rr 0 9 0 19 0 0 0 0 28
Jr(a) 5 0 8 9 0 0 0 0 22
Di(b) 0 0 16 0 0 0 2 0 18
D 12 0 0 0 0 0 0 0 12
rr 0 3 0 7 0 0 0 0 10
Lan 0 0 6 2 0 0 0 0 8
U 0 0 6 1 0 0 0 0 7
Jk(ab) 0 3 0 3 1 0 0 0 7
JMH 0 0 5 1 0 0 0 0 6
Ss 0 0 5 0 0 1 0 0 6
R zR z 0 0 6 0 0 0 0 0 6
Lu(ab) 0 0 4 0 0 0 0 0 4
Oh (Bombay) 0 0 4 0 0 0 0 0 4
rr 0 0 0 2 0 0 0 0 2
K0 0 0 0 2 0 0 0 0 2
766

were integrated into the IRDP in 2009 when the Spanish investigated in one of the patients in whom a complete deletion
Working Party on Rare Donors became an official member. of the RHAG gene was found. There are other phenotypes
Regarding the activity of our program, 246 rare units of that are also very difficult to find in our country, such as K0,
blood were supplied in the period from 2010 to 2014: 122 of McLeod, Co(ab), GE:2, GE:2,3, Rh17, Rh29, Cr(a),
these units were thawed and 124 were fresh (Table 2). Twelve In(b), SC:1, and At(a).
of these units were distributed in response to international In summary, the creation of this Working Party on Rare
requests: 1 Vel (Israel), 5 Di(b) (Sweden), 5 Jr(a) (4 UK Donors in Spain has led to major improvements in recent
and 1 Sweden), and 1 D (Portugal). years. In the last 2 years, two new BTCs (Aragon and Basque
In the last 10 years, all requests but one were filled. The Country) have been incorporated into the Working Party, also
only exception was the case of a woman with an antibody providing a list of blood donors with rare phenotypes. Our
directed against a high-prevalence antigen for which the panel of cryopreserved units currently includes 766 units, and
specificity had not been identified before transfusion. She the list of donors with rare blood types includes 900 blood
was transfused with RBCs from her son and suffered from a donors.
moderate hemolytic transfusion reaction. Some months later, This impressive list of units and donors with rare
the International Blood Group Reference Laboratory (IBGRL) phenotypes is the result of the great effort made by the different
of Bristol (UK) identified a new specificity directed to a new BTCs in the years before the creation of the Spanish Working
antigen termed DOLC in her blood. This antigen belongs to the Party. The union of all these efforts, together with the creation
Dombrock system. of the Spanish program for rare blood donors, allowed us to
At present, we have no active Rhnull donors, but one donor optimize the list of donors and units to improve the service we
and two patients had been identified in the past as carriers offer to hospitals and to patients. In recent years, our donors
of this rare phenotype. The molecular background was have shown a high level of commitment without any incentive

60 I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016


Spanish rare donor program

Table 2. Rare units of blood supplied by the Spanish program for other than the satisfaction of altruistically helping the patients
rare blood donors, 20102014.
needing a transfusion from a rare blood donor. We believe that
Phenotype Cryopreserved Fresh Total the best way to achieve this level of commitment is to provide
Kp(a+b) 48 23 71 the donors with the most complete information possible about
k 19 25 44 the significance of being a carrier of a rare blood group.
Vel 5 22* 27
To determine the efficient use of these special units of
Lu(a+b) 6 15 21
blood, further work is needed to reinforce the habit of reporting
Fy(ab) 4 13 17
the final destination and outcome of the units supplied.
Yt(a) 4 8 12
Although our panel covers most of the phenotypes that are
PP1Pk 6 2 8
clinically important, we continue searching for others that are
Jr(a) 8 0 8
extremely rare due to their low prevalence. The ISBT Working
U 7 1 8
Party should play a central role in coordinating the search for
Co(a) 2 5 7
these very rare phenotypes with the different members.
Di(b) 2 5 7
R zR z 4 1 5
Eduardo Muiz-Diaz, MD (corresponding author), Coordinator
Oh (Bombay) 4 0 4
of Spanish Working Party on Rare Blood Donors, Head of the
rr 2 2 4 Immunohematology Laboratory, Blood Bank and Tissue Center
D 1 1 2 of Catalonia, Spain, (emuniz@bst.cat); Ana Castro, MD, Head of
rr 0 1 1 the Processing Laboratory, Blood Transfusion Center (BTC) of
122 124 246 Galicia; Elena Flores, MD, Head of the Cryobiology Laboratory,
*1 Israel. BTC of Madrid; Luis Larrea, MD, PhD, Head of the Processing

4 UK, 1 Sweden. Laboratory, BTC of Valencia; Fernando Puente, MD, Head of the

5 Sweden. Immunohematology Laboratory, BTC of Aragon; Marisa Ayape,

1 Portugal. MD, Head of the Processing Laboratory, BTC of Navarra; Miguel


Angel Prez-Vaquero, MD, Production Manager, BTC of Basque
Country, Spain.

I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016 61


For information concerning the National Reference Immunohematology is on the Web!
Laboratory for Blood Group Serology, including the American www.redcross.org/about-us/publications/
Rare Donor Program, contact Sandra Nance, by phone at immunohematology
(215) 451-4362, by fax at (215) 451-2538, or by e-mail at For more information, send an e-mail to
Sandra.Nance@redcross.org. immuno@redcross.org.

62 I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016


Review

Rare donor programs in Switzerland, Germany,


and Austria
H. Hustinx, S. Lejon Crottet, E.A. Scharberg, and C. Weinstock

In 2009, the Working Party on Rare Donors of the German with antibodies against high-prevalence antigens in the
Society of Transfusion Medicine and Immunohematology major reference laboratories and blood services in Germany,
(DGTI), which represents the German-speaking countries Switzerland, and Austria. During the 20-month observation
of Switzerland, Germany, and Austria (Fig. 1), started to period, 56 cases were reported. In 71 percent of these cases,
develop a joint database for rare donors. The database was antibodies against Kpb, Vel, Lub, Yta, or Coa were detected,
implemented in 2011 in Berne, Switzerland, and is maintained confirming the direction of the early programs. In recent
by the Swiss Red Cross Blood Service (public access: http:// years, high-throughput molecular methods were developed
www.iblutspende.ch/en/rare-donors/rare-donors.html). and implemented. These methods have made it possible to
Germany and Switzerland, which have mostly Caucasian test donors for high-frequency alleles independent of the
populations, started rare donor programs in the 1990s availability of specific antisera, which often were not available
(Table 1), focusing on donors negative for Kpb, Vel, Lub, and in appropriate quantity and quality. At present, about 1100
Yta. In 2003, Seltsam et al.1 conducted a survey for patients donors with rare blood types are listed in the DGTI database
(Table 2). Most of these donors are registered by the Swiss
Blood Services. The listing of German and Austrian donors
has not yet been completed.
In order to keep blood donation on a volunteer basis, no
incentives are offered for rare donors.
In 2012, Switzerland imported four red blood cell (RBC)
units with the Lu(b) phenotype and exported two RBC units
with the Jk(ab) phenotype. Seventeen rare blood units [1
Lu(b), 3 K+k, 5 Yt(a), 8 Vel] were shipped within the
Springe
country. According to the German authorities no RBC units
were imported in 2012. Germany exported 302 units to
Hagen European countries, although the number of rare phenotypes
included was not specified. From 2012 to 2014, 136 (37
Germany cryopreserved) units were shipped domestically [44 Lu(b),
71 Yt(a), 3 Vel, 9 AnWj, 4 Co(a), 1 Kp(b), 2 PP1Pk,
1 R zR z (CCD.EE), 1 GE:2]. Requests for rare phenotypes are
not systematically documented by most blood services, thus
Baden-Baden no exact data are provided for unfilled requests.
Ulm Neither in Germany nor in Switzerland were intentionally
Munich Vienna incompatible transfusions reported in the case where a request
for rare units could not be filled. It is likely that other measures,
Austria
Berne Zurich such as administration of erythropoietin or inclusion in an
autologous blood program, were taken. This information,
Switzerland however, is scarce and laboratories normally cannot track
these cases.
There is one known donor with the Rhnull phenotype in
Fig. 1. Blood service centers in Austria, Germany, and Switzerland
that reported rare donor screening programs. Centers (noted with
Switzerland. This donor carries the allele RHAG*01N.02.
squares) also store frozen red blood cell units. In Germany, one donor with Rhnull and one with the Rhmod

I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016 63


H. Hustinx et al.

Table 1. Historic and current testing methods and consequent donors identified in rare donor programs in Austria, Switzerland,
and Germany

Number of
Program location/organizer Years donors tested Method of testing
Austrian Red Cross Blood Center, Vienna, Austria C. Jungbauer et al. 20072015* 25,000 Molecular

Interregional Blood Transfusion SRC Ltd., Berne, Switzerland H. Hustinx et al. 20102011 52,000 Serologic
20112012 40,000 Serologic
2013 35,000 Serologic
20112015 21,000 Molecular

Red Cross Blood Service, Institute, Zurich, Switzerland B. Frey et al. 20122015 40,000 Molecular

Red Cross Blood Service West Institute, Hagen, Germany B. Just et al. 19961998 22,000 Serologic
20042005 2000 Serologic
20082009 5600 Serologic
2009today
>250 Serologic

2012today >4000 Molecular

Bavarian Red Cross Blood Service Institute, Munich, Germany J. Burkhart et al. 19992000 5500 Serologic
19992000 5000 Serologic
19992000 5000 Serologic

Red Cross Blood Service NSTOB Institute, Springe, Germany F.F. Wagner et al. 20052007# 3400 Molecular
20072013** 64,000 Molecular
2013today** >22,000 Molecular

Red Cross Blood Service Baden-Wrttemberg, Hessen Institute, Baden-Baden, Germany 19982012 15,000 Serologic
E.A. Scharberg et al.
20132014 35,000 Serologic
20132014 150,000 Serologic

Red Cross Blood Service Baden-Wrttemberg, Hessen Institute Ulm, Ulm, Germany 20092010# 2500 Molecular
I. von Zabern et al.

*Six multiplex polymerase chain reactions (57 primer pairs) for a single blood donor2; agarose gel electrophoresis.

In-house method.

Matrix-assisted laser desorption/ionization, time-of-flight (MALDI-TOF). 3

Only donors of African or Asian origin are included.

MALDI-TOF; testing for VEL*01N/01N was added in 2014.


#
Manual testing using agarose gels.4
** Semi-automated testing using pooled capillary electrophoresis; CO switched to VEL in August 2013.

64 I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016


Rare donor programs: Switzerland, Germany, and Austria

Rare donor screening/number of donors identified


Lu(b) Kp(b) Yt(a) Co(a) LU:14 Vel MAR Fy(ab) Ss U Lan K0
X X X X X 30 additional alleles are tested
20 2 68 31 8
X Additional antigens were tested
X
X
X X X X X 22 additional alleles are tested
35 10 60 46 13
X X X X X X Additional alleles are tested
44 6 86 28 7 3
X
X
X X X X X
X X
8 3 19 11 17 62 3
X X X X X Additional alleles are tested
5 0 9 12 0
X X
X X
X X
5 0 14 0 1 0
X X X X
X X X X
X X X X
209 11 190 146 12
X X
X X X X
X
12 1 5 8 3

X X X X

2 0 13 3

I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016 65


H. Hustinx et al.

Table 2. Rare donors listed in the German Society for Transfusion References
Medicine and Immunohematology (DGTI) database as of 2015
1. Seltsam A, Wagner FF, Salama A, Flegel WA. Antibodies
Phenotype Number of donors
to high-frequency antigens may decrease the quality of
K+k 316 transfusion support: an observational study. Transfusion
Yt(a) 214 2003;43:15636.
Lu(b) 145 2. Jungbauer C, Hobel CM, Schwartz DW, Mayr WR. High-
throughput multiplex PCR genotyping for 35 red blood cell
Fy(ab) 105
antigens in blood donors. Vox Sang 2012;102:23442.
Co(a) 101
3. Meyer S, Vollmert C, Trost N, et al. High-throughput Kell, Kidd,
Vel 39 and Duffy matrix-assisted laser desorption/ionization, time-
rr 39 of-flight mass spectrometry-based blood group genotyping of
Kp(b) 28 4000 donors shows close to full concordance with serotyping
and detects new alleles. Transfusion 2014;54:3198207.
rr 26
4. Wagner FF, Bittner R, Petershofen EK, Doescher A, Muller TH.
Lu(ab) 10 Cost-efficient sequence-specific priming-polymerase chain
MAR (Rh:51) 7 reaction screening for blood donors with rare phenotypes.
PP1P k
3 Transfusion 2008;48:116973.
R zR z 3
D 3 Hein Hustinx, Interregional Blood Service Swiss Red Cross,
SsU 2 Bern, Switzerland; Sofia Lejon Crottet, PhD, Interregional Blood
Service Swiss Red Cross, Bern, Switzerland; Erwin A. Scharberg,
SsU+var 2
MD, German Red Cross Blood Service Baden-Werttemberg,
Jk(ab) 2
Baden-Baden, Germany; Christof Weinstock, MD (corresponding
Kx (McLeod) 2 author), German Red Cross Blood Service Baden-Werttemberg
Jr(a) 2 Hessen, Institute Ulm, Helmholtzstrasse 10, 89081 Ulm, Germany,
Lan 2 c.weinstock@blutspende.de.
Di(b) 1
Lw(ab+) 1
Oh (Bombay) 1
Pk (P; GLOB:1) 1
Rhnull 1

phenotype are known. The molecular background of the Rhnull


donor is under investigation. The Rhmod phenotype is caused
by heterozygosity for the RHAG*01N.03 allele and a new allele
with a single nucleotide polymorphism causing an amino
acid substitution located at the transmembrane/intracellular
border. This donor carries Rh antigens at a very low level that
can be detected by absorption and elution methods only.

66 I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016


Review

The United Kingdom national rare donor panel


N.M. Thornton

The first incarnation of the national rare donor panel The UK National Frozen Blood Bank
(NRDP) in the United Kingdom was established in 1952,
when 1800 donors (100 from each of the 18 blood transfusion A selection of rare units are frozen and stored at the UK
centers around the UK) were fully typed by the International National Frozen Blood Bank (NFBB), which is situated at
Blood Group Reference Laboratory (IBGRL) in London, the National Health Service Blood and Transplant (NHSBT)
to enable the UK Blood Transfusion Services to meet the Liverpool center. A special code applied to the database record
demands for patients with what were considered special and of rare donors ensures that when they donate, their units are
rare blood types.1 What was considered a rare type in 1952 flagged for possible freezing, separated from general blood
was very different than what is perceived as a rare type today, stocks, and processed as rare units. Donations are sent to the
however. The purpose of the panel was to provide blood for NFBB from all the NHSBT centers across England and also
patients whose serum contained antibodies that made finding from several regular rare donors from the Scottish and Welsh
compatible blood difficult. Therefore, although the definition of blood services.
a rare blood type has changed significantly, the core purpose Red blood cell (RBC) units are frozen using a high-glycerol,
of the NRDP has remained the same. automated method (ACP 215, Haemonetics, Glasgow, UK).
In 1967, coinciding with the development of the World Upon freezing, units are stored between 60C and 80C
Health Organization (WHO) International Rare Donor Panel and given a shelf life of 10 years. For some more exquisitely
(IRDP),2 the IBGRL revised the NRDP by removing donors rare phenotypes, the units may be kept beyond the assigned
with what were now considered relatively common blood expiry, especially if there are no known donors of that type
types and adding donors with blood types of great rarity. currently available.
In the late 1970s, a mass screening program using As of March 2014, the NFBB had approximately 600
microplate methodology was initiated at the National Blood frozen rare units. Over the past 9 years, the NFBB averaged
Service South London center to identify donors whose cells around 120 units frozen and 90 units thawed per year (Gina
lacked high-prevalence antigens. This screening program has MacLaren, personal communication, June 17, 2015).
developed over the years to include additional antigens and
provides the largest source of rare donors in the UK. How We Find Rare Donors
The UK NRDP consists of all the rare donor categories
included on the IRDP, with the addition of the following: The main method of finding rare donors in the UK is
rr K; rr K; R1R1 k; R2R2 k; and rr k. Although not through screening programs, using predominantly serologic
considered rare by IRDP criteria, these phenotypes are difficult methods. The main program carried out at the NHSBT
to find in the UK. South London center screens donations in batches of 640
using a method based on the microplate method described
The Current Panel by Gale, Rowe, and Northfield.3 Only donations from
previously unscreened donors are selected for testing. These
The current UK NRDP consists of approximately 2000 are predominantly group O, but also some group A donors
active donors. In the period from April 2012 to the end of are selected. Table 1 shows the current screening undertaken
March 2014, 540 new rare donors were added to the panel. at the South London center. Samples from donors identified
In the same period, 216 rare units were issued for clinical as having a rare phenotype are then sent to the IBGRL for
use; 174 of those units were for patients within the UK and confirmation testing.
the remaining 42 units were shipped internationally. Only two In addition to this mass screening, all K+ donations
rare blood requests could not be filled: one for In(b) units identified through routine donation testing are typed for k. For
and the other for e, SsU units; both were international many years (until 1995), the Welsh blood service screened a
requests. portion of their donors for Lub, Kpb, Yta, Coa, and Vel.4 They

I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016 67


N.M. Thornton

Table 1. Testing performed through the rare donor screening growth restriction. There were no signs of hemolytic disease
program in South London
of the fetus and newborn.
Specificity Antibody type Dilution Method
Co a
Human 1:20 IAT Incentives for Rare Donors
Ge Monoclonal 1:20 Saline
I Human 1:20 Saline
The blood supply in the UK is sustained through the
k Human 1:20 Saline
generosity of non-remunerated, voluntary blood donors. This
Kpb Monoclonal 1:150 IAT
situation helps to maintain the safest possible blood supply
Lu b
Monoclonal 1:20 Saline
and, to that effect, there are no incentives offered to rare
Wrb Monoclonal 1:80 Saline
blood donors in the UK. When a donor is identified as having
Vel Human 1:50 Papain
a rare blood type, the person receives a letter explaining the
Lan Human 1:100 IAT
uniqueness and importance of his or her blood. Consent is
Yta Human 1:15 IAT
also requested for the addition of the donor to the NRDP and
IAT = indirect antiglobulin test.
IRDP. The letter also provides information that the donor may
be called upon in special situations to donate for particular
now screen approximately 90 donations a week for Lua, Lub, patients. Rare donors are asked to actively encourage any
Kpa, Kpb, and k (Heather Davies, personal communication, eligible family members to become blood donors. They may be
April 30, 2015). Routine Rh typing (D, C, c, E, e) facilitates the given special consideration regarding donation appointment
detection of rr, rr, Rhnull, D , and other Rh variants. Oh times, and every effort is made to make an appointment
phenotype donors are detected via anomalous ABO grouping available when it is most convenient for them, including
results, and other rare phenotypes such as Jk(ab), Fy(ab), creating additional appointment slots.
and SsU are detected through routine extended typing If blood from a rare donor is identified as being required
strategies. The routine antibody screening test, carried out on for a particular patient, and the donor is assessed as being
all donations, can also lead to the detection of rare donorsfor eligible to donate, the donor will receive a phone call from a
example, the rare p and Pk phenotypes are identified through dedicated rare donor consultant hematologist and asked if he
their associated antibodies that are present in the serum of or she is able to give blood on this occasion. Our rare donors
such individuals. Similarly, a small portion of rare donors understand the importance of being available to donate when
are former patients, ascertained as lacking a high-prevalence they receive the call, and we are grateful for their willingness
antigen because of the presence of the corresponding antibody to go out of their way to save and improve the lives of others,
in their serum.1 When such a patient is identified and his or her especially when called upon to do so at short notice.
health permits, efforts are made to recruit this individual as a
donor and also to recruit family members of this individual, Rhnull Donors
especially siblings, in the hope of finding additional donors
with the same rare phenotype. Only one UK donor with the extremely rare Rhnull
phenotype is currently known. The donor was identified in
Incompatible Transfusion Cases 2003 and shortly after being discovered was contacted to
donate a unit of blood for urgent shipment to Portugal for life-
Data regarding transfusion of incompatible units in rare saving transfusion to a newborn.5 The donor has the regulator
cases was not actively collected in the UK until more recently type of Rhnull, genotype RHCE*ce/ce, RHD*01N.01/01N.01,
and still continues to be difficult to obtain. From April 2012 to RHAG*532A/532A.6
the end of March 2014, one case of incompatible transfusion
was reported to the NHSBT (Dr. Nay Win, personal Summary
communication, May 27, 2014). A pregnant patient with
thalassemia intermedia presented with weak anti-Jra (and The UK NRDP has been in existence for over 60 years to
weak anti-CW) in her serum. Intravenous immunoglobulin was ensure that blood can be provided for specific patients with the
administered at 0.4g/kg/day for 3 days prior to transfusion rarest blood requirements. The combined approach of routine
of 2 units of Jr(a+) RBCs and the RBCs were tolerated well. antigen typing and screening for high-prevalence antigens
Delivery was by caesarean section due to intrauterine fetal enables the vast majority of rare blood requests to be filled

68 I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016


UK rare donor panel

within the UK and also provides us the opportunity to help References


other countries in need of rare blood that cannot be sourced
1. The Lister Institute annual report. Bushey, UK: The Lister
locally. Institute,1952:145.
2. Poole J. The screening, identification and use of rare blood. Vox
Acknowledgments Sang 2002;83(Suppl 1):99100.
3. Gale SA, Rowe GP, Northfield FE. Application of a microplate
antiglobulin technique to determine the incidence of donors
The author would like to thank Mr. Alan Gray of NHSBT lacking high frequency antigens. Vox Sang 1988;54:1723.
South London center for his dedication to the success of the 4. Porter L, Davies H, Mohabir L. Screening donations for rare
rare donor screening program and providing data for this red cell phenotypes [Abstract]. Transfus Med 2001;11:54.
report; Miss Gina MacLaren for providing data and also for 5. Irwin K, Melanaphy R, Warke N, et al. A new Rhnull blood donor
and the International Rare Donor Panel [Abstract]. Transfus
the wonderful job carried out by her and the NFBB team; Dr. Med 2003;13(Suppl 1):25.
Nay Win, NHSBT Consultant Hematologist, for providing the 6. Bruce LJ. Red cell membrane transport abnormalities. Curr
incompatible transfusion data; Dr. Rekha Anand, NHSBT Opin Hematol 2008;15:18490.
Consultant Hematologist, for the vital role she plays in
recruiting our rare donors; and, most importantly, our rare Nicole M. Thornton, MSc, Head of Red Cell Reference, International
donors from all over the UKthank you for always answering Blood Group Reference Laboratory, Red Cell Reference Department,
NHS Blood and Transplant, 500 North Bristol Park, Northway,
the call to donate and saving the lives of others.
Filton, Bristol, BS34 7QH, UK, nicole.thornton@nhsbt.nhs.uk.

I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016 69


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70 I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016


Review

The American Rare Donor Program


C. Flickinger

The American Rare Donor Program (ARDP) was formed ARDP received 2359 requests; of these, 2203 (93.6%) received
in 1998 as a collaborative effort between the AABB and the rare units. Units were provided for 1235 of 1366 (90.4%)
American Red Cross (ARC) to provide rare blood for patients requests for high-prevalence antigennegative blood (Fig.
in need. Both organizations began rare donor databases in 2) and for 921 of 943 (97.7%) requests for multiple common
the 1960s; the ARC Rare Donor Registry and the AABB Rare antigennegative blood. Liquid units were provided for 72.6
Donor File were merged into the ARDP database in 1998 as percent of these requests. In addition, the ARDP provided 45
a result of this effort. Currently, the ARDP has phenotype units for international requests (Table 1).
information on more than 59,000 active rare donors submitted
by its 86 member facilities located in the United States as well Transfusion of Incompatible Blood
as one member facility each in Italy, Kuwait, and Brazil (Fig.
1). ARDP members consist of Red Cross and AABB-accredited The ARDP is aware of one patient case in which
immunohematology reference laboratories. incompatible blood was transfused because of the inability
The ARDP maintains two categories of rare red cell to identify the patients antibody and to thus find compatible
donors: those negative for a high-prevalence antigen (<1:1000) blood. This patient developed hyperhemolysis following a
and those negative for multiple common antigens (per two
defined sets of criteria; set 1 consists of R1R1, R2R2, R0R0, or
Table 1. International requests supported by the American Rare
rr; K; Fy(a) or Fy(b); Jk(a) or Jk(b); and S or s; set Donor Program from 2012 to 2014
2 consists of R1R1, R2R2, or rr; K; and Fy(ab).1 Of the total Number
active donors in the ARDP, 8.0 percent are those negative for of units
Country ABO/D Phenotype provided
a high-prevalence antigen and 91.5 percent are those negative
Australia O pos C K Fy(ab) S 2
for multiple common antigens. Interestingly, approximately
two-thirds of the requests to the ARDP are for patients Canada O pos K E I 2

requiring units negative for a high-prevalence antigen and one- O pos Lan 3

third of the requests are for patients requiring units negative O pos Jr(a) 1
for multiple common antigensshowing the great disparity A pos C E K Fy(ab) M S V Kp(a) 4
Go(a)
between the registered donors and the patient requests.
O pos GE:2,3 1
ARDP members search for rare donors from their
geographical areas who meet the rare phenotype criteria and, O neg Co(a) Lu(a) 4

with donor approval, submit the donor information for entry B pos E c K Fy(a) Jk(a) M s Cw 1

into the ARDP database, which is housed at the ARC facility B pos K Jk(ab) 3
in Philadelphia. ARDP members requiring rare units for O pos E c K Fy(b) S Jk(ab) 2
patients submit requests to the Philadelphia site. The ARDP China O pos C E Fy(ab) 8
database is then searched for members who have donors of the Ireland O pos C K Fy(a) S s U 1
requested phenotype, and those members are contacted for O neg C E K Fy(a) S s U 1
available liquid or frozen units or eligible donors. Each blood O pos C K S s U 2
collection member has the ability to recruit donors, freeze rare Netherlands O pos f C K Fy(ab) Jk(b) S
w
5
units when donated, and ship liquid and frozen units when
Scotland O pos K N S s U 1
requested. The ARDP database stores information on requests
South Africa O neg C E K Fy(a) Yt(a) 2
made and requests filled; monthly and annual reports are
Sweden A pos U 1
provided to the members on their activity.
A neg K U 1
From 2012 to 2014, 10,271 rare donors were submitted to
45
the ARDP and more than 4219 rare units were provided. The

I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016 71


C. Flickinger

1
1
1
3
1 2 3 2
1 1
3 1
5
1 4 4
4 2
2 4
1
1 2 2
7
3
2
2
1 1
2 States with 5 ARDP Members
2 1
States with 4 ARDP Members
3 States with 3 ARDP Members
3
States with 2 ARDP Members
3
States with 1 ARDP Member

1 each in Brazil, Italy, Kuwait, and Puerto Rico

Fig. 1 Location of the 86 members of the American Rare Donor Program, 2015.

delayed hemolytic transfusion reaction attributable to three Incentive Programs for Rare Donors
subsequently identified antibodies and an unidentified
alloantibody directed against a high-prevalence antigen, ARDP donors receive a welcome letter, a donor card with
resulting from previous transfusions.2 Investigative studies at donor name and identified rare phenotype, and a pamphlet
the ARC National Reference Laboratory, at the International titled One in a Million explaining the importance of being a
Blood Group Reference Laboratory in Bristol, and at the ARC rare donor. In addition, ARDP members may initiate facility-
National Molecular Laboratory failed to identify the antibody specific incentive programs for their rare donors being mindful
to the high-prevalence antigen. Even with the concomitant of the U.S. regulations mandating that blood donations be
use of high-dose eculizumab, further transfusions resulted voluntary.
in massive hemolysis of the patients red blood cells despite
a negative direct antiglobulin test. The patient developed Rhnull Donors
life-threatening anemia, and was treated with oxygen,
corticosteroids, and erythropoietin (EPO) while further The ARDP has one Rhnull donor who is group A. This
transfusions were withheld. The patients condition improved. donor is very aware of the rarity of her blood and has donated
Following discharge and with continued use of EPO, the numerous units, both autologous and homologous, over the
patient donated autologous units for future use. years. Her RH locus has not been molecularly characterized.

72 I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016


American Rare Donor Program

D+ U 350 References
332
137 1. American Rare Donor Program, Standard Operating
Yt(a) 134
Procedure, Version Date: 4/1/2013.
120
Rare Rh 109 2. Gupta S, Fenves A, Nance ST, Sykes DB, Dzik WS. Hyper-
k 119 hemolysis syndrome in a patient without a hemoglobinopathy,
118
unresponsive to treatment with eculizumab. Transfusion 2015;
109
Js(b) 99 55:62328.
69
EhrB 59
Cynthia Flickinger, MT(ASCP)SBB, Managing Editor, Immuno-
62
Kp(b) 58 hematology, American Red Cross Biomedical Services, Musser Blood
Vel 60 Center, 700 Spring Garden St., Philadelphia, PA 19123, Cynthia.
54
Flickinger@redcross.org.
56
Lu(b) 54
39
D U 25
39
Jk(ab) 31
26
Hy 23
Total Requests
25
GE:2 22 Filled Requests
23
Di(b) 18
22
Co(a) 22
15
I 9
13
Jo(a) 10
13
PP1Pk 12
12
Lan 4
11
Jr(a) 9
11
Lu(ab) 8
7
Rare Kell 6
6
At(a) 3
5
Oh (Bombay) 5
4
EhrS 3
4
Cr(a) 2
4
GE:2,3 3
2
Tc(a) 2
1
P 1
1
Gy(a) 0
1
SC:3 0

Fig. 2 Phenotypes of received and filled requests through the


American Rare Donor Program from 2012 to 2014.

I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016 73


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74 I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016


C o m m e n ta r y

Miracles do happen: meeting the challenges


of providing rare blood through the American
Rare Donor Program
C. Flickinger

It begins with a phone call or an e-mail. I have a patient as well as its international colleagues when they are unable
with sickle cell disease with anti-X who will need chronic to provide units for a patient. From 2005 to 2015, the ARDP
transfusions beginning. We have a pregnant female sched- provided 19,528 rare RBC units for 9683 patient requests
uled to deliver in 3 months who has anti-X and a history of within the U.S. and 172 units for 77 requests internationally.
hemorrhaging during delivery. There is a fetus who will need However, at times, providing rare blood requires a miracle to
intrauterine transfusions because of maternal anti-X. We overcome the many challenges, some of which are highlighted
will be managing a transplant patient with anti-X . . . can you in this article.
help? One obvious challenge is finding the especially rare units
Requests to the American Rare Donor Program (ARDP) or eligible donors when a request is made. Communication
are managed 24/7 by the American Red Cross (ARC) National with the ARDP members provided knowledge as to which
Reference Laboratory for Blood Group Serology (NRLBGS) members had coveted K0 donors, which members had En(a)
staff in Philadelphia, Pennsylvania. Staff members at the 89 units in their freezer, or how to obtain the most rare Rhnull units
ARDP member Immunohematology Reference Laboratories through a personal conversation with our only known Rhnull
(IRLs) across the United States and abroad submit requests to donor, who was very knowledgeable about her phenotype and
the Philadelphia staff who relay the request to the other ARDP its impact on her life as well as its rarity and need. She donated
members who then search their inventories for available units numerous autologous as well as allogeneic units that she
or eligible donors.1,2 This process works well; the ARDP has a gladly released for other patients with the stipulation that she
93.8 percent fill rate (average of years 20042014), which is be notified of the request and that the patient truly needed
defined as providing at least 1 unit of rare blood for each request. Rhnull blood (i.e., had the respective antibodies). She would
While units of rare blood can be frozen to meet a future need, then donate to ensure an adequate supply of units for herself as
frozen units have a propensity to break in transit. Therefore, well as for others: a truly altruistic, informed rare donor!
it is preferable, if time allows, that requests for exceptionally An associated challenge is providing especially rare blood
rare blood of which there are less than a handful of donors, in a time-sensitive situation. One of the most miraculous of
requests for blood for a patient requiring chronic transfusions the international experiences involved the turnaround time
whose serum contains multiple antibodies necessitating rare to fill a request from New Zealand for a pregnant female who
blood and requiring a more extensive search, and international was group A, D+ with anti-Rh17, for whom they requested 2
requests for which shipping may involve multiple flights and units of fresh (less than 5 days old), group O, D RBCs
customs clearance be handled by the recruitment, collection, for the baby. The ARDP received the request on a Tuesday. At
and shipping of liquid red blood cell (RBC) units. It is these that time, there were eight registered group O, D donors
requests that require an intense search to find the one donor in the ARDP database; however, only three donors could be
who matches a patient and then to ship that precious unit contacted immediately on that Wednesday. All three donors
across state and sometimes international borders. These are attempted to donate; one was deferred. The 2 liquid units
the requests for which a phone call or an e-mail to the ARDP were shipped to Philadelphia on Friday and shipped to New
manager starts a different process: one that requires a high Zealand, arriving 7 days from the initial requestnot quite 5,
degree of collaboration between shipping and receiving but not bad! One interesting aside was that one of the donated
facilities. units was antibody-positive, requiring complete antibody
The ARDP serves its member facilities, non-member identification prior to its release; this extra testing could
facilities that use a member as a portal to access the program, have affected the turnaround time. Interestingly, the plasma

I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016 75


C. Flickinger

from this patient was then sent to the NRLBGS to be used There is a great difference in managing a request for a
as a source for screening donors. This shows the high level patient with anti-hrB in 2015 compared with 2008. In 2008, the
of collaboration within the members of the ARDP as well as ARDP had access to only a small database of 80 characterized
within the international community. donors who had been genotyped in response to patient needs
Another challenge to the ARDP is providing blood that rather than through mass screening. With the variability of
is negative for low-prevalence antigens, typically along with the RHD and RHCE genotypes, these 80 donors represented
the blood also being negative for many common and possibly many diverse heterozygous combinations that frequently did
uncommon antigens. Ever-declining antisera resources for not match the genotypes of the needy patients, which tended
typing units, especially antisera for some of the low-prevalence to be more homozygous. More characterized donors were
antigens, has affected the ability of laboratories to perform needed. In addition, without the genotype of the patient, it was
these typings on units. Many frozen common antigen not possible to provide appropriate units. Although the donor
negative units sit in inventory; however, because they have database began growing with the use of the mass-screening
not been tested for low-prevalence antigens and resources are platforms in 2008 and 2009, patient testing lagged behind.
unavailable, they are not usable for patients who have made an My initial response to a request for a patient with anti-hrB or
additional antibody to a low-prevalence antigen. Only through anti-hrS was, Has the patient been genotyped? At that time,
subsequent donations and molecular testing can these donors most replies were negative, to which the importance of having
be tested and their units be made available for such requests. In the patients RHD and RHCE characterized was stressed to
the U.S., it is relatively easy to send a segment from an untested enable the ARDP to provide the best match for this patient.
unit to the requesting ARDP facility for use in crossmatching Efforts to educate the physicians and lab staff were productive,
or possibly in typing if the facility happens to have an antisera and the list of molecularly tested patients grew with the list
source. However, when providing units internationally, this of molecularly tested donors. The ARDP, with the help of the
practice is not expeditious or economically feasible. One molecular testing, was moving in the right direction, in being
patient in the UK, who was in sickle cell crisis, required a total able to provide genotype-matched units; it just wasnt quite
of 12 units of group O, CEKFy(ab)sJs(a) RBCs (two there yet. In this transition period, some requests for patients
different requests, 2 weeks apart). Twelve liquid units were were answered with a report of the patients molecular results,
found at five different ARDP facilities; however, not all of the but no identified donors. However, in the past few years, a
units had been typed for Jsa. Processing this request ran into a request for a patient with anti-hrB was answered with a report
weekend, and, at one facility, on-call staff was asked to go into of the patients molecular results, a search for tiered genotype-
the site and type the liquid units for Jsa to ensure shipment on matched donors, and very likely a liquid unit from a donor
Monday morning. It was a group effort, and all requested units who just happened to come in and donate. These were
were provided. the miracles that became more frequent with the advent of
The introduction of molecular testing into the testing using molecular methods. Many hrB patients are well
immunohematology arena in 2008 not only allowed for the served by this testing. However, hrS patients are not quite as
identification of more common and uncommon antigens on a fortunate, since far fewer hrS donors have been identified.
single donor sample, including low-prevalence antigens such Therefore, it is crucial that blood centers continue to invest in
as Jsa, Kpa, and Lua, but also provided a means to further building the cohort of donors with full RH characterization for
characterize RH alleles of patients and donors, which greatly these patients.
enhanced the ability to identify hrB donors and provide One of the classic stories of the impact of molecular
genotype-matched units to patients with anti-hrB. As we have testing on providing units is that of a 4-year-old patient
come to learn, there are many RHCE variants that cause the who, in 2005, was in need of a splenectomy. He was group
hrB phenotype; antisera for hrB have never been characterized O, D+ with anti-Jka and anti-hrB, which had not been
and are unreliable sources for screening donors. Educating characterized. Because he was E, the physician requested
the reference laboratory staff as well as physicians to the that the units be E as well. At that time, only four donors
importance of molecular testing is ongoing. But over the last in the U.S. had been identified as being hrB by serology:
8 years, this initiative has increased the number of patients donors in California, Illinois, Florida, and Wisconsin. The
tested and the number of donors identified and has made it four donors were contacted, and all attempted to donate; one
possible to provide tiered genotype-matched units for patients was deferred. Samples from the patient and the four donors
for whom few other options are available.3 were sent to a molecular laboratory where the patients RHD

76 I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016


Challenges to the ARDP

alleles were characterized as RHD*01/RHD-DIIIa-CE(4- flights; shipments that missed the scheduled truck delivery;
7)-D, and his RHCE alleles were found to be RHCE*ce733G/ timing the shipment to make the last ferry ride from Seattle to
RHCE*ce48C,733G,1006T. The RHD allele DIIIa-CE(4-7)-D Victoria, British Columbia; and the absence of customs officials
and the RHCE allele RHCE*ce48C,733G,1006T are often onsite to receive and process the imported shipment added to
co-inherited, and the haplotype is often referred to as rS. delays and alternate plans as well. It was a logistical nightmare
Although none of the donors were an exact match, three of at times, but through numerous communication channels, the
the four donor samples were either RHD*01 or RHD-DIIIa- blood did arrive.
CE(4-7)-D and homozygous for RHCE*ce48C,733G,1006T; Much was learned through trial and error on how best
therefore, RHD*01 RHCE*ce48C,733G,1006T homozygotes to expedite shipments. Having made shipping arrangements
or r'S homozygotes, both of which were Tier 2 matches for the for an international shipment only to find that the units
genotype of this patient. The liquid units were shipped, and were held up in processing changed how I managed these
the surgery took place. In 2010, the ARDP received another shipments; all units were physically observed before finalizing
request for this patient. At that time, there were 74 hrB Tier 1 the arrangements to ensure that the units were typed, tagged,
or 2 genotype-matched donors, making the search for units for and physically ready to ship. A call to the courier for flight
this patient much easier. information typically began with the courier asking, When
Holidays and vacations were no exception to requests for can you have the blood shipment ready? However, the best
rare blood, adding the challenge of short-staffed laboratories planning focused on the question, When does the flight leave?
and modified flight schedules. In November 2013, while baking Once the flight departure time was established, we would
pumpkin pies on the day before Thanksgiving, I received a work backwards from the flight time to allow driving time to
phone call from the on-call physician for a Chicago hospital, the airport, the 2-hour required time for the shipment to be at
where a patient was in need of I RBC units; the physician the airport prior to flight time, and the time to pack the units.
was calling from a beach in Florida where he was visiting Although the blood was shipped in boxes that were validated
family. Requests had been sent through the ARDP with no for 48-hour transit time, either with wet ice for liquid units or
responses received from ARDP member facilities, the patient dry ice for frozen units, the goal was always to minimize the
was worsening, and, of course, it was a holiday. Knowing that time that the blood was in transit.
lab staffing was limited because of the holiday, and always Although many challenges exist, miracles do happen,
with ARDP information at my side, I phoned the handful of and rare blood is shipped through the collaboration of many
sites with registered I donors and found 3 units, which were individuals and facilities. My sincere thanks go to all who
then shipped. For another case, during Christmas week of answer the phone; respond to the e-mail; take the time to
2010, I was at home on the phone with the manager of the ARC contact donors; collect, process, and test units; pack and ship
National Molecular Laboratory (also at home), searching for the boxes; and provide rare blood in any way to the patients in
units for a patient with end-stage renal disease who was group need. You are a special group who make the ARDP the success
O, D+ with anti-C, anti-E, and anti-hrB. The patients RHD and that it is.
RHCE alleles had been characterized, and her haplotype was
determined to be DIIIa-ceS/rS. At that time, there were about References
20 donors who would have been a Tier 1 or 2 genotype match
1. Flickinger C. REGGI and the American Rare Donor Program.
for her; however, only 1 unit was available; it was shipped on Transfus Med Hemother 2014;41:3425.
December 27, 2010. Despite transfusion, the patient expired 2. Meny GM, Flickinger C, Marcucci C. The American Rare Donor
on January 1, 2011. Program. J Crit Care 2013;28:110.e9110.e18.
Shipping rare blood is not without its logistical challenges: 3. Keller MA, Horn T, Crowley J, Nance S, Meny G, Flickinger
C. Genotype compatibility tables for matching patients and
shipments of rare blood have been delayed because of a donors for RH variants [Abstract]. Transfusion 2013:53(Suppl
tropical storm in the Gulf of Mexico preventing a flight from S2);176A.
Miami to Trinidad; or because of a dog on board a flight, which
prevented dry ice from being on the same plane; or because Cynthia Flickinger, MT(ASCP)SBB, Managing Editor, Immuno-
the scheduled flight switched to a smaller plane that had hematology, American Red Cross Biomedical Services, Musser Blood
Center, 700 Spring Garden St., Philadelphia, PA 19123, Cynthia.
restrictions on the amount of dry ice that could be transported.
Flickinger@redcross.org.
Dealing with time zones across the U.S. and across the
Atlantic or Pacific; pilots not allowing dry ice on passenger

I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016 77


Announcements

NIH Annual Symposium Announcements

September 21, 2016


6th Annual Red Cell Genotyping Symposium. 2016: Clinical Steps. The Department of Transfusion Medicine, Clinical
Center, National Institutes of Health (NIH), and the BloodCenter of Wisconsin are co-hosting this symposium on the NIH
campus in Bethesda, Maryland. For information, registration fee, and advance registration, contact Phyllis Kirchner,
BloodCenter of Wisconsin, P.O. Box 2178, Milwaukee, WI 53021-2178; e-mail: phyllis.kirchner@bcw.edu; or visit our Web site:
www.bcw.edu/rcg2016

September 22, 2016


35th Annual Immunohematology and Blood Transfusion Symposium. The Department of Transfusion Medicine, Clinical
Center, National Institutes of Health (NIH), and the American Red Cross are co-hosting this symposium on the NIH campus in
Bethesda, Maryland. There is no registration fee, but advance registration is encouraged. Contact Karen Byrne, NIH/CC/DTM,
Bldg. 10/Rm. 1C711, 10 Center Drive, MSC 1184, Bethesda, MD 20892-1184; e-mail: kbyrne@cc.nih.gov; or visit our Web site:
http://www.cc.nih.gov/dtm/research/symposium.html

78 I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016


Announcements, cont.

Masters (MSc) in Transfusion and Transplantation Sciences


at
The University of Bristol, England

Applications are invited from medical or science graduates for the Master of Science (MSc) degree in
Transfusion and Transplantation Sciences at the University of Bristol. The course starts in October
2016 and will last for 1 year. A part-time option lasting 2 or 3 years is also available. There may also
be opportunities to continue studies for PhD or MD following the MSc. The syllabus is organized
jointly by The Bristol Institute for Transfusion Sciences and the University of Bristol, Department of
Pathology and Microbiology. It includes:
Scientific principles of transfusion and transplantation
Clinical applications of these principles
Practical techniques in transfusion and transplantation
Principles of study design and biostatistics
An original research project

Application can also be made for Diploma in Transfusion and Transplantation Science or a Certificate
in Transfusion and Transplantation Science.

The course is accredited by the Institute of Biomedical Sciences.

Further information can be obtained from the Web site:


http://ibgrl.blood.co.uk/MSc/MscHome.htm

For further details and application forms please contact:

Dr Patricia Denning-Kendall
University of Bristol
Paul OGorman Lifeline Centre
Department of Pathology and Microbiology
Southmead Hospital
Westbury-on-Trym, Bristol BS10 5NB, England
Fax +44 1179 595 342, Telephone +44 1779 595 455, e-mail: p.a.denning-kendall@bristol.ac.uk.

I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016 79


Announcements, cont.

Online Specialist in Blood Bank (SBB)


Certificate and Masters in Clinical Laboratory
Management Program
Rush University
College of Health Sciences
Continue to work and earn graduate credit while the Rush University SBB/MS program prepares
you fo the SBB exam and the Diplomat in Laboratory Management (DLM) exam given by ASCP
Board of Certification! (Please note acceptable clinical experience is required for these exams.)

Rush University offers online graduate level courses to help you achieve your career goals.
Several curricular options are available. The SBB/MS program at Rush University is currently accepting
applications for Fall 2016. For additional information and requirements, please visit our website
at: www.rushu.rush.edu/cls/

Rush University is fully accredited by the Higher Learning Commission (HLC) of the North
Central Association of Colleges and Schools and the SBB Certificate Program is accredited by the
Commission on Accreditation of Allied Health Education Programs (CAAHEP).

Applications for the SBB/MS Program can be submitted online at the folowing website:
http://www.rushu.rush.edu/admiss/hlthadm.html

Contact: Yolanda Sanchez, MS, MLS(ASCP)CMSBB, Director, by e-mail at Yolanda_Sanchez@rush.edu


or by phone at 312-942-2402 or Denise Harmening, PhD, MT(ASCP), Director of Curriculum
by e-mail at Denise_Harmening@rush.edu

80 I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016


Announcements, cont.

The Johns Hopkins Hospital Specialist in Blood Bank Technology Program

The Johns Hopkins Hospital was founded in 1889. It is located in Baltimore, Maryland, on the original founding site,
just 45 minutes from Washington, DC. There are approximately 1,000 inpatient beds and another 1,200 outpatient visits
daily; nearly 600,000 patients are treated each year.

The Johns Hopkins Hospital Transfusion Medicine Division is one of the busiest in the country and can provide
opportunities to perform tasks that represent the entire spectrum of Immunohematology and Transfusion Medicine
practice. It provides comprehensive support to all routine and specialized areas of care for surgery, oncology, cardiac,
obstetrics, neonatal and pediatric, solid organ and bone marrow transplant, therapeutic apheresis, and patients with
hematological disorders to name a few. Our intradepartment Immunohematology Reference Laboratory provides
resolution of complex serologic problems, transfusion management, platelet antibody, and molecular genotype testing.

The Johns Hopkins Hospital Specialist in Blood Bank Technology Program is an onsite work-study, graduate-level
training program for certified Medical Technologists, Medical Laboratory Scientists, and Technologists in Blood Banking
with at least 2 years of full-time Blood Bank experience.

The variety of patients, the size, and the general intellectual environment of the hospital provide excellent opportunities
for training in Blood Banking. It is a challenging program that will prepare competent and knowledgeable graduates who
will be able to effectively apply practical and theoretical skills in a variety of employment settings. The Johns Hopkins
Hospital Specialist in Blood Bank Technology Program is accredited by the Commission on Accreditation of Allied Health
Education Programs (CAAHEP). Please visit our website at http://pathology.jhu.edu/department/divisions/transfusion/
sbb.cfm for additional information.

Contact: Lorraine N. Blagg, MA, MLS(ASCP)CMSBB


Program Director
E-mail: lblagg1@jhmi.edu
Phone: (410) 502-9584

The Johns Hopkins Hospital


Department of Pathology
Division of Transfusion Medicine
Sheikh Zayed Tower, Room 3100
1800 Orleans Street
Baltimore, Maryland 21287

Phone (410) 955-6580


Fax (410) 955-0618
Web site: http://pathology.jhu.edu/department/divisions/transfusion/index.cfm

I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016 81


A dv e rtise m e nts

82 I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016


Advertisements, cont.

Becoming a Specialist in Blood Banking (SBB)


What is a certified Specialist in Blood Banking (SBB)?
Someone with educational and work experience qualifications who successfully passes the American Society for Clinical Pathology
(ASCP) board of registry (BOR) examination for the Specialist in Blood Banking.
This person will have advanced knowledge, skills, and abilities in the field of transfusion medicine and blood banking.
Individuals who have an SBB certification serve in many areas of transfusion medicine:
Serve as regulatory, technical, procedural, and research advisors
Perform and direct administrative functions
Develop, validate, implement, and perform laboratory procedures
Analyze quality issues preparing and implementing corrective actions to prevent and document issues
Design and present educational programs
Provide technical and scientific training in transfusion medicine
Conduct research in transfusion medicine
Who are SBBs?
Supervisors of Transfusion Services Managers of Blood Centers LIS Coordinators Educators
Supervisors of Reference Laboratories Research Scientists Consumer Safety Officers
Quality Assurance Officers Technical Representatives Reference Lab Specialists
Why become an SBB?
Professional growth Job placement Job satisfaction Career advancement
How does one become an SBB?
Attend a CAAHEP-accredited SBB Technology program OR
Sit forthe examination based on criteria established by ASCP for education and experience.
However: In recent years, a greater percentage of individuals who graduate from CAAHEP-accredited programs pass the SBB exam.
Conclusion: The BEST route for obtaining an SBB certification is . . . to attend a CAAHEP-accredited Specialist in Blood Bank Technology
Program.
Additional information can be found by visiting the following Web sites: www.ascp.org, www.caahep.org, and www.aabb.org
Contact the following programs for more information:

Onsite or
: Online
Program Contact Name Phone Contact E-mail Contact Web Site Program

American Red Cross, Southern California Region Catherine Hernandez 909-859-7496 Catherine.Hernandez@redcross.org www.redcrossblood.org/socal/communityeducation
American Red Cross, Central OH Region Joanne Kosanke 614-253-2740 ext. 2270 Joanne.Kosanke@redcross.org none
Blood Center of Wisconsin Phyllis Kirchner 414-937-6271 Phyllis.Kirchner@bcw.edu www.bcw.edu
Blood Systems Laboratories Marie P. Holub 602-996-2396 mholub@bloodsystems.org www.bloodsystemslaboratories.org :
Community Blood Center/CTS Dayton, Ohio Nancy Lang 937-461-3293 nlang@cbccts.org www.cbccts.org/education/sbb.htm :
Hoxworth Blood Center, University of Cincinnati Pamela Inglish 513-558-1275 Inglishpf@ucmail.uc.edu www.grad.uc.edu
Medical Center
Indiana Blood Center Jayanna Slayten 317-916-5186 jslayten@indianablood.org www.indianablood.org :
Johns Hopkins Hospital Lorraine N. Blagg 410-502-9584 lblagg1@jhmi.edu http://pathology.jhu.edu/department/divisions/transfusion/sbb.cfm
LifeShare Blood Centers Katrina Billingsley 318-673-1546 Katrina.billingsley@lifeshare.org
NIH Clinical Center Blood Bank Karen Byrne 301-496-8335 Kbyrne@mail.cc.nih.gov www.cc.nih.gov/dtm
OneBlood Marjorie Doty 727-568-1214 Marjorie.doty@oneblood.org http://medical.oneblood.org/-education/applicationform.stml :
Rush University Laurie Gillard 312-942-2402 Laurie_Gillard@rush.edu www.rushu.rush.edu/cls :
University Medical Center New Orleans Leslie M. Granier 504-702-3558 Leslie.Granier@lcmchealth.org www.mclno.org/webresources/index.html
University of Texas Medical Branch at Galveston Janet Vincent 409-772-3055 jvincent@utmb.edu www.utmb.edu/sbb :
University of Texas SW Medical Center Lesley Lee 214-648-1785 lesley.lee@utsouthwestern.edu www.utsouthwestern.edu/education/school-of-health-professions/ :
programs/certificate-programs/medical-laboratory-sciences/index.html
Walter Reed Army Medical Center William Turcan 301-295-8605 William.Turcan@med.navy.mil www.militaryblood.dod.mil/Fellow/default.aspx
William.turcan@us.army.mil

Revised April 2016

I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016 83


Advertisements, cont.

National Reference Laboratory National Neutrophil Serology Reference Laboratory


for Specialized Testing
Our laboratory specializes in granulocyte antibody detection
Diagnostic testing for: and granulocyte antigen typing.
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include:
Refractoriness to platelet transfusion
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Methodologies employed:
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For further information, contact: For further information, contact:

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American Red Cross Biomedical Services American Red Cross Biomedical Services
Musser Blood Center Neutrophil Serology Laboratory
700 Spring Garden Street 100 South Robert Street
Philadelphia, PA 19123-3594 CLIA licensed St. Paul, MN 55107 CLIA licensed

84 I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016


Advertisements, cont.

Reference and Consultation Services IgA Testing

Antibody identification and problem resolution IgA testing is available to do the following:
HLA-A, B, C, and DR typing Identify IgA-deficient patients

HLA-disease association typing Investigate anaphylactic reactions

Paternity testing/DNA Confirm IgA-deficient donors


Our ELISA for IgA detects protein to 0.05 mg/dL.
F or infor mation , c ontac t :
F or additional infor mation c ontac t :

Mehdizadeh Kashi
Sandra Nance (215) 451-4362
at (503) 280-0210
or e-mail:
or write to: Sandra.Nance@redcross.org

Tissue Typing Laboratory or write to:


American Red Cross Biomedical Services
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700 Spring Garden Street
3131 North Vancouver
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Portland, OR 97227
ATTN: Sandra Nance
CLIA licensed, ASHI accredited CLIA licensed

National Reference Laboratory Donor IgA Screening


for Blood Group Serology
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Immunohematology Reference Laboratory
Gel diffusion test that has a 15-year proven track record:
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Approximately 90 percent of all donors identified as
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IgA deficient by this method are confirmed by the more
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I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016 85


Immunohematology
Instructions for Authors
I. GENERAL INSTRUCTIONS b. Use short headings for each column needed and capitalize first letter of first
Before submitting a manuscript, consult current issues of Immunohematology for style. word. Omit vertical lines.
Number the pages consecutively, beginning with the title page. c. Place explanation in footnotes (sequence: *, , , , , **, ).
8. Figures
II. SCIENTIFIC ARTICLE, REVIEW, OR CASE REPORT WITH
a. Figures can be submitted either by e-mail or as photographs (5 7 glossy).
LITERATURE REVIEW
b. Place caption for a figure on a separate page (e.g. Fig. 1 Results of), ending
A. Each component of the manuscript must start on a new page in the following with a period. If figure is submitted as a glossy, place first authors name and
order: figure number on back of each glossy submitted.
1. Title page c. When plotting points on a figure, use the following symbols if possible:
2. Abstract l l s s n n.
3. Text 9. Author information
4. Acknowledgments a. List first name, middle initial, last name, highest degree, position held,
5. References institution and department, and complete address (including ZIP code) for all
6. Author information authors. List country when applicable. Provide e-mail addresses of all authors.
7. Tables
8. Figures III. EDUCATIONAL FORUM

B. Preparation of manuscript A. All submitted manuscripts should be approximately 2000 to 2500 words with
1. Title page pertinent references. Submissions may include:
a. Full title of manuscript with only first letter of first word capitalized (bold 1. An immunohematologic case that illustrates a sound investigative approach with
title) clinical correlation, reflecting appropriate collaboration to sharpen problem solving
b. Initials and last name of each author (no degrees; all CAPS), e.g., M.T. JONES, skills
J.H. BROWN, AND S.R. SMITH 2. Annotated conference proceedings
c. Running title of 40 characters, including spaces B. Preparation of manuscript
d. Three to ten key words 1. Title page
2. Abstract a. Capitalize first word of title.
a. One paragraph, no longer than 300 words b. Initials and last name of each author (no degrees; all CAPs)
b. Purpose, methods, findings, and conclusion of study 2. Text
3. Key words a. Case should be written as progressive disclosure and may include the
a. List under abstract following headings, as appropriate
4. Text (serial pages): Most manuscripts can usually, but not necessarily, be divided i. Clinical Case Presentation: Clinical information and differential diagnosis
into sections (as described below). Survey results and review papers may need ii. Immunohematologic Evaluation and Results: Serology and molecular
individualized sections testing
a. Introduction Purpose and rationale for study, including pertinent iii. Interpretation: Include interpretation of laboratory results, correlating
background references with clinical findings
b. Case Report (if indicated by study) Clinical and/or hematologic data and iv. Recommended Therapy: Include both transfusion and nontransfusion-
background serology/molecular based therapies
c. Materials and Methods Selection and number of subjects, samples, items, v. Discussion: Brief review of literature with unique features of this case
etc. studied and description of appropriate controls, procedures, methods, vi. Reference: Limited to those directly pertinent
equipment, reagents, etc. Equipment and reagents should be identified in vii. Author information (see II.B.9.)
parentheses by model or lot and manufacturers name, city, and state. Do not viii. Tables (see II.B.7.)
use patients names or hospital numbers.
d. Results Presentation of concise and sequential results, referring to IV. LETTER TO THE EDITOR
pertinent tables and/or figures, if applicable A. Preparation
e. Discussion Implication and limitations of the study, links to other studies; if 1. Heading (To the Editor)
appropriate, link conclusions to purpose of study as stated in introduction 2. Title (first word capitalized)
5. Acknowledgments: Acknowledge those who have made substantial contributions 3. Text (written in letter [paragraph] format)
to the study, including secretarial assistance; list any grants. 4. Author(s) (type flush right; for first author: name, degree, institution, address
6. References [including city, state, Zip code and country]; for other authors: name, degree,
a. In text, use superscript, Arabic numbers. institution, city and state)
b. Number references consecutively in the order they occur in the text. 5. References (limited to ten)
7. Tables 6. Table or figure (limited to one)
a. Head each with a brief title; capitalize the first letter of first word (e.g., Table
1. Results of) use no punctuation at the end of the title. Send all manuscripts by e-mail to immuno@redcross.org

86 I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016


Immunohematology
Instructions for Authors | New Blood Group Allele Reports

A. For describing an allele which has not been described in a peer-reviewed publication and for which an allele name or provisional allele name has been assigned by the
ISBT Working Party on Blood Group Allele Terminology (http://www.isbtweb.org/working-parties/red-cell-immunogenetics-and-blood-group-terminology/blood-group-
terminology/blood-group-allele-terminology/)

B. Preparation
1. Title: Allele Name (Allele Detail)
ex. RHCE*01.01 (RHCE*ce48C)
2. Author Names (initials and last name of each (no degrees, ALL CAPS)

C. Text
1. Case Report
i. Clinical and immunohematologic data
ii. Race/ethnicity and country of origin of proband, if known
2. Materials and Methods
Description of appropriate controls, procedures, methods, equipment, reagents, etc. Equipment and reagents should be identified in parentheses by model or lot and
manufacturers name, city, and state. Do not use patient names or hospital numbers.
3. Results
Complete the Table Below:
Phenotype Allele Name Nucleotide(s) Exon(s) Amino Acid(s) Allele Detail References
e weak RHCE*01.01 48G>C 1 Trp16Cys RHCE*ce48C 1

Column 1: Describe the immunohematologic phenotype (ex. weak or negative for an antigen).
Column 2: List the allele name or provisional allele name.
Column 3: List the nucleotide number and the change, using the reference sequence (see ISBT Blood Group Allele Terminology Pages for reference sequence ID).
Column 4: List the exons where changes in nucleotide sequence were detected.
Column 5: List the amino acids that are predicted to be changed, using the three-letter amino acid code.
Column 6: List the non-consensus nucleotides after the gene name and asterisk.
Column 7: If this allele was described in a meeting abstract, please assign a reference number and list in the Reference section.
4. Additional Information
i. Indicate whether the variant is listed in the dbSNP database (http://www.ncbi.nlm.nih.gov/snp/); if so, provide rs number and any population frequency information, if available.
ii. Indicate whether the authors performed any population screening and if so, what the allele and genotype frequencies were.
iii. Indicate whether the authors developed a genotyping assay to screen for this variant and if so, describe in detail here.
iv. Indicate whether this variant was found associated with other variants already reported (ex. RHCE*ce48C,1025T is often linked to RHD*DIVa-2)

D. Acknowledgments

E. References

F. Author Information
List first name, middle initial, last name, highest degree, position held, institution and department, and complete address (including ZIP code) for all authors. List country when
applicable.

I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016 87


Journal of Blood Group Serology and Molecular Genetics
P ublished quarterly by The A merican N ational R ed C ross

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**

**

Card Number: Security Code: Exp. Date: /

**Subscription form and billing information may be mailed to above address or e-mailed to Immuno@redcross.org
or via phone to Marge Manigly at 215-451-4902

THIS FORM MUST ACCOMPANY PAYMENT.

88 I M M U N O H E M ATO LO GY, Vo l u m e 32, N u m b e r 2, 2 016


NON PROFIT
U.S. POSTAGE
PAID
Musser Blood Center AMERICAN
700 Spring Garden Street RED CROSS
Philadelphia, PA 19123-3594

(Place Label Here)