Download 2011 Extended red blood cell antigen matching for

I M M U N O H E M AT O L O G Y
Extended red blood cell antigen matching for transfusions in
sickle cell disease: a review of a 14-year experience from a
single center
_3045
1732..1739
Michele LaSalle-Williams, Rachelle Nuss, Tuan Le, Laura Cole, Kathy Hassell, James R. Murphy,
and Daniel R. Ambruso
BACKGROUND: Alloimmunization to red blood cell
(RBC) blood group antigens is a major complication for
patients with sickle cell disease (SCD), which limits the
usefulness of RBC transfusion. Here, we report our
experiences with extended RBC antigen matching for
SCD patients.
STUDY DESIGN AND METHODS: Records for 99 SCD
patients transfused only with the extended matching
protocol between 1993 and 2006 were reviewed.
Patients and donors were phenotyped for 20 blood
group antigens and RBC units that were negative for
antigens not expressed by the recipient were provided.
When necessary, mismatches were allowed at Lea, Leb,
Fyb, and MNSs to meet requirements for antigens
regarded as the most clinically significant. Matched
RBC units (6946) were provided to 99 patients (mean,
70 units/patient; range, 1-519 units/patient). Eliminating
mismatches, 90% of the transfusions matched all other
negative antigens.
RESULTS: Seven alloantibodies were detected in
seven patients resulting in 7% alloimmunized at a rate
of 0.1 antibodies per 100 units transfused. Three recipients who developed antibodies were D mosaic and
would have been mistyped with serologic techniques.
Alloimmunization was decreased compared to ABO
and/or D matching at our institution and others. Twelve
autoantibodies and no severe hemolytic transfusion
reactions were reported.
CONCLUSION: Exact matching for ABO, Rhesus, Kell,
Kidd, and Fya and extending this match whenever possible is an effective strategy to reduce alloimmunization
to RBC antigens. Consideration should be given to
exploring this conclusion further with a controlled, multiinstitutional trial to determine efficacy, cost-benefit
analysis, and reproducibility of this approach.
1732 TRANSFUSION
Volume 51, August 2011
W
orldwide, sickle cell disease (SCD) affects
individuals of many different racial and
ethnic groups, but in the United States,
most patients are African American.1,2
Although hydroxyurea administration has improved outcomes for some patients with SCD, transfusion therapy
remains a mainstay for the treatment of severe, acute
complications and a critical strategy to reduce the chronic
morbidity and mortality associated with the disease. Associated with transfusion therapy is the risk of alloimmunization to minor red blood cell (RBC) blood group antigens,
which increases with repeated transfusions. The mechanism for alloimmunization with SCD patients is, for the
most part, related to the lack of compatibility of RBC antigens between the donors of largely European background
and the African American recipients;3-7 the alloimmunization rate in the SCD patient population ranges between 18
and 46%.3-12 The presence of RBC alloantibodies creates
the potential for serologic incompatibility, makes the
selection of appropriate units for future transfusions more
ABBREVIATION: SCD = sickle cell disease.
From the Bonfils Blood Center, Denver, Colorado; the Departments of Pediatrics and Medicine, The University of Colorado
at Denver and Health Sciences Center, The Children’s
Hospital, and the Colorado Sickle Cell Treatment and
Research Center, Aurora, Colorado; and the Division of Biostatistics and Informatics, National Jewish Health, Denver,
Colorado.
Address correspondence to: Daniel R. Ambruso, MD, Bonfils
Blood Center, 717 Yosemite Street, Denver, CO 80230; e-mail:
[email protected].
Supported by The Bonfils Blood Center, The Colorado
Sickle Cell Treatment and Research Center, and The Stacey
Marie True Memorial Trust.
Received for publication October 8, 2010; revision received
December 14, 2010, and accepted December 15, 2010.
doi: 10.1111/j.1537-2995.2010.03045.x
TRANSFUSION 2011;51:1732-1739.
MINOR ANTIGEN MATCHING FOR SICKLE CELL DISEASE
difficult, delays the use of a potentially life-saving therapy,
and presents a risk for hemolytic transfusion reactions,
some potentially life-threatening.4,7,13,14 RBC autoantibody formation is higher when alloimmunization has
occurred.4,9,11,15-20
Currently, there is no consensus for matching RBC
antigens when transfusing patients who are not yet
alloimmunized.2,21 A review by the College of American
Pathologists completed several years ago concludes that
most laboratories surveyed do not routinely perform phenotyping of RBC antigens for SCD patients beyond A, B,
and D, and those that did, most commonly limited the
extended matching to C, E, and K.21 Recent technological
advances in completing RBC antigen typing by molecular
rather than serologic techniques may change this
approach. Many centers caring for SCD patients allow for
the initial development of alloantibodies before organizing matching beyond ABO and D.21 Some providers advocate additional but limited matching for C, E, and K since
50% of alloantibodies demonstrated in SCD patients are
against these antigens.10,11,13 Castro and colleagues10 have
suggested a protocol for extended matching for additional
antigens such as Fya and Jkb to C, E, and K could further
reduce the rate of alloimmunization.
In this article, we describe our experience with an
extended antigen-matched RBC transfusion protocol for
SCD patients receiving care through a regional, universitybased comprehensive SCD program. The program was
initiated in 1978, and reports for SCD patients on chronic
transfusion therapy demonstrated a significant decrease
in the rate of alloimmunization in patients with SCD.4,22
Results for extended RBC antigen matching in a larger
number of patients for a wider variety of indications since
1993 are presented here.
MATERIALS AND METHODS
Patient population
Patients were identified either through a neonatal screening program or when they sought care at the Colorado
Sickle Cell Treatment and Research Center at a later age
and received transfusions at The Children’s Hospital
Denver, University of Colorado Hospital (Denver), and
Memorial Hospital (Colorado Springs). Chart review was
completed under a protocol approved by the Colorado
Multiple Institutional Review Board (The Children’s
Hospital, University of Colorado Hospital) and Memorial
Hospital Institutional Review Board. Clinical records
from patients with homozygous HbSS, HbSC, HbS
b-thalassemia (b+ or b°) were reviewed from January 1,
1993, to December 31, 2006. Only those patients who
received transfusions under the extended matching protocol as described were included in the analysis (n = 99)
and none had antibodies documented before their first
transfusion. For each patient, age, sex, SCD categories,
RBC phenotype, and indications for transfusion were
recorded. The extent of phenotype match was analyzed by
a computer program structured to evaluate each unit of
RBCs transfused to each patient enrolled. Adverse events
associated with any transfusion were noted. Reactions
were reported and documented by the clinical transfusing
service caring for the patients and evaluated by the transfusion service at the transfusing hospital. Event characteristics were defined using descriptions in the Technical
Manual.23 Finally, the presence and characteristics of any
allo- or autoantibody detected during the matching protocol were documented as described below. Control data
for SCD patients receiving transfusions matched for ABO
and D only were obtained from records before our
extended matching and previously reported.4
Laboratory testing and extended matching
Patients’ RBCs were phenotyped for multiple blood group
systems and antigens including ABO; Rh (C, c, D, E, e); Kell
(K, k); Duffy (Fya, Fyb); Kidd (Jka, Jkb); Lewis (Lea, Leb); and
MNS (M, N, S, s) with commercial reagents by standard
serologic techniques.4,23 To assure accuracy of typing, tests
were repeated twice as previously described.4 Antibody
screening was completed at visits to the comprehensive
clinic, before each transfusion, or 3 to 4 weeks after each
transfusion in the case of chronically transfused patients
in preparation for the next transfusion. Phenotyping and
antibody testing were performed in the AABB-accredited
Immunohematology Reference Laboratory at Bonfils
Blood Center. Antibody detection during the period of
study involved a three-cell antibody screen on patient
serum or plasma using low-ionic-strength-saline or polyethylene glycol to enhance antibody-antigen interactions
with standard tube technique.4,23 Reactivity was documented with standard agglutination grading or hemolysis.
A screen was positive if agglutination of reagent screening
cells occurred after immediate spin, after incubation at
37°C, or at AHG phase. If the screening test was positive,
antibody identification was completed using at least a
10-cell panel testing at immediate spin, 37°C, and AHG
phase. For autoantibody evaluation, DAT with polyspecific and monospecific reagents were used. Specificities
for autoantibodies were completed with panels as noted
above with comparison to the patient’s RBC phenotype.
Cold autoantibodies were evaluated with cold antibody
screen at 4°C, thermal amplitude studies, reactivity with
cord blood cells, or more recently, a pathologic cold antibody test at 30°C.
Since 1978, donors for this program have been tested
for the RBC antigens noted above by standard serologic
techniques.4,23 Phenotypes were confirmed on a second
occasion, and more than 120,000 donors have been
studied and used as a source for transfusion products
since 1978.
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For each transfusion request, attempts were made to
match each negative antigen in the recipient with a negative antigen in the donor.4 Mismatches were allowed
when necessary for MNSs, Fyb, and Lea or Leb because of
lower immunogenicity and risk for sensitization or the
infrequent incidence of hemolytic transfusion reactions.
During the course of the study, eight patients received 13
units of RBCs matched only for ABO and D. The urgency
of the complications precluded waiting for extended
matching (see Results). Compatibility testing for each unit
was completed with patient’s serum by standard techniques. When alloantibodies occurred, units negative for
the requisite antigen were provided. A clinically significant antibody was defined as one that is frequently associated with a hemolytic transfusion reaction, a notable
decrease in survival of RBCs, or hemolytic disease of the
newborn and would include antibodies to C, D, E, c, e, K,
k, Kpa, Fya, Fyb, Jka, Jkb, S, or s. Initially, washed or frozen,
deglycerolized RBCs were provided for the transfusions in
this program, and subsequently, leukoreduced units were
used. When possible, especially for chronic transfusions,
products negative for sickle trait were provided for
transfusion.
For statistical comparison of extended matching with
other matching strategies, the exact likelihood ratio test
was used, adjusting for multiple comparisons by Bonferroni employing a computer program (Stat Exact, Cytel,
Inc., Cambridge, MA). For multiple comparisons, each test
must be a p value of 0.0023 or less.
RESULTS
Ninety-nine patients managed exclusively under the
extended-match protocol met the inclusion criteria for
this study. The characteristics of the study population data
are displayed in Table 1. First transfusions were provided
from infancy to adult years with a mean age of 7.4 years.
Slightly more than half of the patients were males. Most
patients had homozygous sickle cell anemia (HbSS); a
small number (14%) had HbSC or HbS b-thalassemia. The
mean interval between the first and last transfusion was
4.8 years. None of the patients received hydroxyurea
during the time of this study. Major indications for transfusion are listed in Table 1.
The total number of units of RBCs administered to the
group was nearly 7000 with a mean of 70 transfusions per
patient, a median of 16, and a range of 1 to 519 units
transfused (Table 1). The range of units transfused is also
listed in quartiles. The majority of patients (57/99)
received intermittently administered transfusions defined
as transfusion support lasting less than 3 months for an
acute SCD complication. Thirty percent had only chronically administered transfusions. A small number of
patients (11/99) had periods of both intermittent and
chronic transfusions. In all, 50 patients received simple,
direct transfusion; 30, RBC exchange or erythrocytapheresis; and 19, both types of transfusion during their
clinical course. While the program was flexible enough to
provide RBC components with an extended match on
TABLE 1. Demographics, patient characteristics, and numbers of transfusions for patients receiving extended
matching for transfusions
Demographics
Evaluable patients
Male/female
Median age (years) of first transfusion (mean age)
Range
Disease type*
HbSS
HbSC
HbS b-thalassemia
Indications for transfusion†
Acute chest syndrome
Vaso-occlusive crises
Cerebrovascular accident and/or abnormal findings on CNS evaluation
(including radiologic or Doppler flow studies)
Aplastic crises
Splenic sequestration
Surgery
Priaprism
Other
Transfusions received†
Total number of units transfused
Mean number of units per patient
Range of number of units transfused
* Number of patients (%).
† Number of complications (%).
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Volume 51, August 2011
99
53/46
6.6 years (7.4)
5 months-19 years, 7 months
Number of patients
85
11
3
Number of complications
52
40
25
23
24
16
7
15
(%)
86
11
3
(%)
25.7
19.8
12.3
11.9
11.9
7.9
3.5
7.4
6946
70
1-519
First quartile, 1-3; second quartile, 3-16;
third quartile, 17-111; fourth quartile, 131-519
MINOR ANTIGEN MATCHING FOR SICKLE CELL DISEASE
most occasions, a few transfusions (13 RBC units in eight
patients) were released with only ABO, D typing because
of the clinical situation (see Materials and Methods). The
severity and acuity of the complication did not allow time
for delivery of extended-matched units and the transfusions were matched for ABO, D. None of these patients
developed auto- or alloantibodies.
As described under Materials and Methods, our strategy was to match units transfused as closely as possible.
However, this goal was not always possible. When necessary, mismatches were allowed for antigens which have a
lower risk for alloimmunization or whose antibodies do
not cause immediate hemolytic transfusion reactions.
Considering data for each unit transfused to the patient
group, 2354 units of 6946 (34%) were exactly matched for
all antigens not present on the patient’s cells. Table 2 summarizes mismatching by antigen. The most frequent antigens mismatched were Fyb, Lea, and Leb, M, and S. Jka was
mismatched in a frequency higher than other antigens
with C/c, E/e, K/k, and Fya mismatched in less than 2% of
the transfusions. Considering mismatches, 39% of the
transfusions had one mismatch, 14.4% two mismatches,
and 12.8% three mismatches. When mismatches were permitted at Lea, Leb, M, N, and Fyb, 6217 units matched
exactly, a rate of 90% of transfused units.
Seven of the 99 transfused patients developed one
alloantibody each (Table 3). The mean number of transfu-
TABLE 2. Percentage of transfusions
mismatched by antigen
Antigen
D
C
c
E
e
K
k
Fya
Percentage of
transfusions
mismatched
0
0.1
0.8
1.8
0.8
1.3
0.2
1.25
Antigen
Fyb
Jka
Jkb
M
N
S
s
Lea
Leb
Percentage of
transfusions
mismatched
44.6
8.2
0.3
6.5
3.6
8.6
4.4
5.5
11.9
sions for these patients was 54 (median, 62 transfusions;
range, 15-85 transfusions). One was in the second quartile
for number of transfusions, three in the third, and three in
the fourth quartile. Six of the seven had more than 17
transfusions. These antibodies included anti-Lea, antiKpa, anti-M, and anti-D mosaic. The patient who developed the anti-Lea experienced a mild decrease in expected
survival of transfused cells reported by the transfusion
service without other symptoms or signs, a reaction that is
rare for this antibody. Anti-Kpa was not an antigen routinely tested in our protocol but can result in delayed
transfusion reactions and hemolytic disease of the
newborn both of which are mild to moderate in severity.23
Anti-M is not usually associated with hemolytic transfusion reactions.23 No antibodies to Fyb were detected. With
any serologic matching protocol, mosaic D will likely be
typed as D positive and the resultant sensitization would
be expected. Considering all antibodies in our current
study, 7% of the patients became alloimmunized with a
rate of 0.1 antibodies per hundred units transfused
(Table 4). However, excluding patients with mosaic D who
would have been mistyped by usual serologic procedures,
4% of patients were determined to have alloantibodies at a
rate of 0.05 antibodies per hundred units transfused. With
both analyses, the percentage of patients alloimmunized
and rate of antibodies were significantly different
(p < 0.00005) from our historical control group (see
Table 4). The new alloantibodies were easily detected and
subsequent transfusions were not significantly delayed in
any patient. In addition to the comparison with our own
historical controls, significant differences in both the percentage of patients with alloantibodies and the number of
antibodies per 100 units transfused (p < 0.0005) were also
noted between our study group and published studies for
patients receiving ABO- and D-matched units for which
complete comparative data are available (Table 5; Aygun
et al.,9 Castro et al.,10 Sakhalkar et al.11). These studies
provide more contemporary observations and address
limitations for our historical control that are older
than the study group and have possible differences in
TABLE 3. Development of alloantibodies, autoantibodies, and adverse events of transfusions in 99 patients on
extended matching protocol
Alloantibodies
Autoantibodies
Adverse events
Seven alloantibodies, one each in seven patients.
Antigen specificity: one each of Lea, Kpa; two for M; three Rh(D)*.
Twelve patients developed DAT associated with autoantibodies.
Warm (IgG, negative complement): four anti-e; one anti-E; 1 anti-D, three panagglutinins.
Cold (IgM, complement positive): four I-specificity, two unspecified.
Nine of 12 with one autoantibody; 3 of 12 with two autoantibodies (warm and cold).
One patient with both, one autoantibody also had one alloantibody.
Ten patients (10%) had reported reactions to 13 units (0.2% total) transfused.
Five allergic: skin manifestations (hives) only.
Three febrile, nonhemolytic transfusion reactions (>1°C fever).
One moderate citrate reaction during apheresis requiring decreased flow rate and oral calcium.
One reported decrease in survival of RBCs as mild delayed hemolytic transfusion reaction.
* All three patients who developed D alloantibodies were determined to be D mosaic, testing initially as D+.
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LASALLE-WILLIAMS ET AL.
TABLE 4. Alloimmunization in patients treated with extended matching protocol*
Period, reference
Before 1978 (control),
Ambruso et al.4
1979-1983, Ambruso
et al.4
Patient group
Chronic transfusions
n = 85
Chronic transfusions
n = 12
1983-1990, Ambruso
et al.22
1993-2006, Present
report
Chronic transfusions
n = 13
Chronic and intermittent
n = 99
Percentage of
patients immunized
34%
Matching
ABO, D
Extended matching
All had previously received
ABO, D
Extended matching only
Extended matching
Rate (antibodies/100
units transfused)
3.4
25%
0.3
8%
0.08
All—7%†
Eliminate D mosaic—4%†
0.10†
0.06†
* Patients described in each period group were analyzed spearately and not included in the summary for any other group.
† Different from historical control, p < 0.00005.
TABLE 5. Studies evaluating alloimmunization and matching for RBC antigens
Reference
Ambruso et al.4
Rosse et al.6
Vichinsky et al.7
Aygun et al.9
Castro et al.10
Sakhalkar et al.11
Vichinsky et al.13
Sakhalkar et al.11
Tahhan et al.8
Number of patients/transfusions
85/1,941
1,044/—*
107/—
140/3,239†
(pediatric and adult patients)
351/8,939†
387/14,263†
Matching ABO, D only
Percentage alloimmunized/number of
alloantibodies per 100 units transfused
34%/3.4
18-31% (27% in study group)/—
30%/—
37%/2.8†
29%-35%/3.8†
31%/1.7†
Matching extended beyond ABO, D, including C, E, K
Percentage alloimmunized/rate,
Number of patients/transfusions
alloantibodies per 100 units transfused
Extended matching for C, E, K
8-11%/0.5
61/1,830
Extended matching for C, E, K
5%/0.26
113/2,345
Matching extended beyond ABO, D, in addition to C, E, K
Percentage alloimmunized/rate,
Number of patients/transfusions
alloantibodies per 100 units transfused
0/—
Extended matching to K, C, E, S, Fya, Fyb
40/—
* Bar notes data not provided or available.
† Different from results for present report, Table 4, p < 0.00005.
management of SCD, provision of blood products and services, and schedules of transfusions.
During the study period, 12 of the 99 transfused
patients had positive direct antiglobulin tests (DATs) associated with the appearance of autoantibodies (data shown
in Table 3). Almost 60% were warm (immunoglobulin
[Ig]G) and the rest were cold (IgM) antibodies. For warm
autoantibodies, antigen specificities were determined as
described under Materials and Methods with phenotype
comparisons. Cold autoantibodies with I specificity had
maximal reactivity at 4°C, detectable reactivity at RT only,
and negative reactivity with cord blood RBCs. Patients
with autoantibodies tended to receive higher numbers of
transfusions (two in the second quartile, five in the third,
and five in the fourth; mean, 173; median, 76; range,
1736 TRANSFUSION
Volume 51, August 2011
9-519). The appearance of the autoantibodies, particularly
those characterized as warm IgG, were associated with a
short delay in delivery of transfusions to the patients until
the serologic incompatibility was clarified. Ten patients
(Table 3) experienced an adverse event of transfusion with
13 transfusion reactions (0.2% of all transfusions). All were
considered mild by physicians caring for the patients.
DISCUSSION
In spite of the importance of RBC transfusions for treating
the severe complications of this disease, there is no
general agreement about matching strategies for SCD
patients requiring transfusions. Most groups caring for
these patients do not complete matching beyond ABO
MINOR ANTIGEN MATCHING FOR SICKLE CELL DISEASE
and D until alloimmunization occurs. Several studies have
demonstrated that 18% to 47% of patients managed with
this approach develop antibodies at a rate of 1.7 to 3.8
alloantibodies per 100 units transfused (Table 5).4,6,7,9-11
The risk of a significant, even life-threatening transfusion
reaction is increased in sensitized patients.4,7,13 In situations where antibodies are identified, there may be long
delays in identifying suitable units of RBCs compounding
the morbidity of the SCD complications.
Some groups advocate matching for C, E, and K
(Table 5) in addition to ABO, D. Vichinsky and colleagues7
in a retrospective study of ABO- and D-matched transfusions supported this approach with a report that 82% of
antibodies in their patients had specificity for C, E, K, and
Kidd. A retrospective study by Castro and colleagues10 suggested that if matching for C, E, and K were completed,
53% of alloantibodies would be avoided. Sakhalkar and
colleagues11 supported additional matching for C, E, and
K with a report of 113 patients given 2300 units. This
study recorded 5% alloimmunization with a rate of 0.26
antibodies/100 units. In 2001, Vichinsky and coworkers13
reviewed the effects of matching ABO, D, C, E, and K in 61
patients for 1830 transfusions. Eleven percent of the
patients became alloimmunized. A small subset of
patients developed E or Kell antibodies from a total of 29
units not matched for these antigens.
Outcomes from protocols that provide even more
extensive matching have been reported (Table 5). Tahhan
and coworkers8 described a subset of 40 patients matched
for C, c, E, e, k, S, and Fy and given D– units. None developed alloantibodies compared with a control group (46
patients) who received matched and mismatched units
resulting in 30% developing 20 new alloantibodies. The
retrospective study by Castro and colleagues10 suggested
that if C, E, K, S, Fyb, and Jkb were matched, all alloantibodies would have been prevented in the 351 patients
receiving 8939 transfusions.
Our composite experience with extended RBC
matching is summarized in Table 4. Before initiating our
program of extended matching in 1978, our blood center
provided ABO- and D-matched units resulting in an
alloimmunization rate of 34% with 3.4 antibodies per
hundred units transfused. These results are similar to
more contemporary data shown by other groups.6,7,9-11
The patients in our first analysis (n = 12) demonstrated a
small decrease in the percentage of alloimmunization and
a nearly 10-fold reduction in rate of alloantibodies.4 These
patients received chronic transfusions for the more severe
complications of SCD, most had prior exposure to routine
ABO and D only matched transfusions, and several were
difficult to phenotype initially because of mixed-field
reactions. Subsequently, we reported a separate cohort
that included patients receiving chronic transfusions who
were treated only with extended matching protocol.22
Alloimmunization was dramatically reduced by 77%. In
our current study of a third separate group we confirm
and expand our experience with a larger number of
patients (n = 99) over a 14-year period. One limitation of
the comparison of our study data with historical controls
may relate to the time interval between the two. Changes
in sickle cell therapy and provision of blood services may
have varied, limiting the validity of the comparison. None
of the patients included in this study were treated with
hydroxyurea, which has the potential to affect alloimmunization. Most transfusions were with leukoreduced
blood products. Assays used in detecting antibodies were
completed in a small number of laboratories including
our regional reference laboratory providing a consistent
technical approach. Indications for acute or chronic
transfusion therapy have remained consistent over the
course of the study except for those few related to results
with transcranial Doppler testing. Most importantly, the
decrease in percentage of patients sensitized and number
of antibodies per unit transfused was different with our
historical control and three studies matching ABO and D
only, completed contemporaneously with ours. Furthermore, our protocol resulted in lower levels of alloimmunization and rates of antibody formation compared with
programs using intermediate matching with testing for C,
E, and K presented by Vichinsky and colleagues13 and
Sakhalkar and colleagues.11 Our rates of alloantibody formation compared to those of Vichinsky and colleagues
were significantly decreased (p < 0.0007). Finally, our
results are comparable to the one reported study with a
smaller number of patients that extended matching
beyond C, E, and K.8
Our program was flexible enough to meet most transfusion needs for all SCD patients. Only a very small
number of transfusions to this patient group were
matched for only ABO and D because of the urgency of the
indication for transfusion. Autoantibodies were documented in our patients and appeared to be more frequent
than alloantibodies (11.5% of patients and 0.25 autoantibodies per 100 units transfused). Adverse events documented in our study were infrequent and mild.
Blood transfusion for SCD remains an essential and
life-saving therapy and more, not fewer, patients may be
transfused in the future.24 An important consideration
in transfusion therapy for patients with SCD is that, in
the absence of extended matched RBCs, alloantibodies
develop in as many as one-third of these individuals,
which may necessitate expensive searches for appropriate
RBC units and delay potentially life-saving treatment. The
impact of the delay may exacerbate morbidity or mortality
and increase cost of care, issues that have not been
included in most analyses.14,15,18 One of the main objections to extended RBC matching for SCD patients to the
level described by Tahhan and coworkers8 and us4,22 is the
additional cost for identifying suitable donors. While we
did not perform a cost-benefit analysis, we previously
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LASALLE-WILLIAMS ET AL.
described the most significant issue as related to start-up
costs.4 Tahhan and coworkers reported antigen-matched
transfusions for ABO, Rh(C, D, E), Kell, Fya, Fyb, and S in 40
patients and calculated the cost to be 1.5- to-1.8 fold
greater than that for standard ABO and D matching.8 This
study reminds us that it is extremely difficult to put a
dollar value on complications incurred by patients alloimmunized to RBC antigens and their subsequent morbidity.
Furthermore, cost is not the overarching consideration
when supplying the safest blood products to other patient
populations. An additional benefit to our program is that
only 50% of matching requests are directed toward SCD
patients; the remainder of our matching services provide
products to patients with different diseases who have
developed alloantibodies and subsequently require RBC
transfusion.
Several important issues have emerged from our
experience with extended antigen matching. First,
patients with SCD may receive care at multiple institutions, and alloimmunization outcomes may reflect the
divergent approaches in use. This report includes experience with patients transfused only under our protocol.
Second, exactly matching all antigens for which the
patient is negative is neither practical nor necessary. Mismatching may be allowed for some antigens because of
the GATA polymorphism resulting in failure of expression
of Fyb in RBCs but not in other tissues of many African
Americans, the nature of antibodies produced, or the type
of adverse events associated with specific antibodies (Le
and MNS blood group systems). Our data support the
concept that matching for C, E, D, Kell, Kidd, and Fya are
the critical antigens to match and dramatically minimize
alloimmunization. Third, new technology using molecular techniques may be helpful to reduce the risk of alloimmunization by confirming serologic phenotype and
eliminating the ambiguities we encountered with the
mosaic D patients. Moreover, the availability of molecular
techniques for typing multiple RBC antigens in a rapid
multiplexed fashion offers accurate typing of both donors
and patients at a considerably lower cost than serologic
techniques.25 The results from this and other studies and
the potential of molecular typing techniques suggest the
need for a multi-institutional clinical trial to test the efficacy of phenotypically matched transfusions in preventing alloimmunization. Such a trial would incorporate
cost-benefit analysis and clinical outcomes, the results of
which could provide the consensus approach to extended
RBC antigen matching for SCD.
Our results demonstrate that extended matching of
RBC antigens for transfusions in patients with the severe
complications of SCD reduces the extent and rate of
alloimmunization providing safer transfusions in a timely
fashion and should be considered whenever these
patients are transfused. Full acceptance of this approach
may require a controlled clinical trial.
1738 TRANSFUSION
Volume 51, August 2011
ACKNOWLEDGMENTS
The authors thank Robert Chapman, MD; William Dickey, MD;
Kevin Land, MD; Pete Peterson, MD; Peter Lane, MD; Wanda
Boyd, RN; and Donna Dixon, RN, for their support of this protocol
over the years. We also recognize Karen Evans, MT(ASCP) SBB;
Monica LaSarre, MT(ASCP) SBB; Colleen Chiappa, MT(ASCP)
SBB; and the technical staff of the Reference Laboratory and
Transfusion Services, Bonfils Blood Center, for their ongoing
efforts for this program. Shannon Winkelmann, Andy Gerber, and
Christian Billington helped with data collection and analysis.
Finally, we acknowledge the help of Flo Usechek and Christian
Snyder in preparing the manuscript.
CONFLICT OF INTEREST
No conflicts of interest for any author.
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Volume 51, August 2011
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