ORIGINAL RESEARCH
ABO-incompatible platelets are associated with increased
transfusion reaction rates
Natalie Malvik,1,† Judith Leon,1 Annette J. Schlueter ,1 Chaorong Wu,2 and C. Michael Knudson
BACKGROUND: ABO compatibility can affect platelet
transfusion safety and efficacy, and ABO-incompatible
(ABOi) platelets likely increases the risks of transfusion
reactions though the magnitude of this risk is unclear.
STUDY DESIGN AND METHODS: Data collected on
all platelet transfusions administered over 36+ months
were classified based on patient and product ABO blood
group type and merged with a data set that included all
transfusion reactions reported during that period. The
transfusion reaction rates among various subsets was
calculated.
RESULTS: In patients greater than 1 year of age, the
transfusion reaction rate in the ABO-compatible (ABO-
identical) platelet group was 1.0%, while the ABOi
platelet group had an elevated reaction rate of 1.7%. The
increased reaction rate for ABOi platelets held true even
if the analysis were limited to Centers for Disease
Control and Prevention/National Healthcare Safety
Network qualifying reactions or just allergic or febrile
nonhemolytic reactions. The increased reaction rate with
ABOi platelets was independent of unit age. Surprisingly,
major-incompatible transfusions (A/B antigen
incompatible) had the highest rate of reactions, at 2.0%.
During the study period, three acute hemolytic reactions
were reported out of 2522 plasma-incompatible platelet
transfusions (0.12%).
CONCLUSIONS: Our results find that compatible
platelet transfusions have the lowest rate of transfusion
reactions. While hemolytic reactions were observed with
plasma-incompatible transfusions, the rate was low.
Transfusion of ABO antigen-incompatible platelets had
the highest rate of transfusion reactions and resulted in a
transfusion reaction rate 1.5 to 2 times that of ABO
compatible transfusions.
1
S
imilar to red blood cells (RBCs), ABO blood group
antigens are expressed on the surface of platelets, pos-
sibly allowing ABO compatibility to affect platelet trans-
fusion outcomes. In contrast to RBCs, most apheresis
platelets also contain substantial amounts of plasma, which may
contain anti-A or anti-B antibodies that could also lead to com-
plications following transfusion of ABO-incompatible platelets.
For the purposes of this study, ABO-compatible describes a
donor-recipient pair with the identical ABO type while ABO-
incompatible (ABOi) describes a donor-recipient pair with differ-
ent ABO types. The latter term encompasses the following three
subcategories of incompatibility: ABO minor-incompatible
(donor plasma containing antibodies against ABO blood group
antigens on recipient RBC and platelets), ABO major-
incompatible (recipient plasma containing antibodies against
ABO blood group antigens on donor RBC and platelets), and
ABO bidirectional-incompatible (donor and recipient plasma
both containing antibodies against ABO blood group antigens on
each other’s RBC and platelets).
ABBREVIATIONS: ABOi = ABO-incompatible; AHTR = acute
hemolytic transfusion reaction; CDC = Centers for Disease Control
and Prevention; EMRs = electronic medical records; FNHTR =
febrile nonhemolytic transfusion reaction; LIS = laboratory
information system; MRN = medical record number; NHSN =
National Healthcare Safety Network; TACO = transfusion-associated
circulatory overload; TAD = transfusion-associated dyspnea; TRALI
= transfusion-related acute lung injury.
From the 1DeGowin Blood Center, Department of Pathology,
University of Iowa Hospitals & Clinics and 2Biostatistician with the
Institute for Clinical and Translation Research, University of Iowa,
Iowa City, Iowa.
Address correspondence to: C. Michael Knudson, Department
of Pathology, University of Iowa Hospitals and Clinics, 200 Hawkins
Dr., C250 GH, Iowa City, IA; e-mail: c-knudson@uiowa.edu
†
Present address: UMass Memorial Medical Center, Worcester
MA 01655.
Source of support: Department of Pathology, University
of Iowa.
Received for publication October 4, 2019; revision received
December 5, 2019, and accepted December 6, 2019.
doi:10.1111/trf.15655
© 2020 AABB
TRANSFUSION 2020;9999;1–9
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MALVIK ET AL.

ABO-compatible platelet transfusions are generally con- reactions during the study. Our policy is to prioritize giving
sidered optimal, but providing ABO-compatible platelets to neonates ABO-compatible platelets, and the compatibility
all patients is often considered impractical or impossible percentage in children less than 1 year of age was much
and would result in increased product wastage.1,2 Previous higher (77%) than in other age groups. In addition, reaction
studies have shown that ABO-compatible platelets provide a rates in children less than 1 year of age was quite low, with
moderately higher platelet increment than ABOi platelets.3 only one reaction reported in 873 transfusions. For these rea-
ABO-identical platelets have also been shown to reduce the sons, transfusion occurring in patients less than 1 year of age
incidence of platelet refractoriness and HLA antibody pro- were excluded from the analysis. An overview of the study
duction in patients undergoing treatment for leukemia or design is shown in Fig. 1.
Hodgkin’s lymphoma.4 Regarding transfusion reactions,
multiple case reports have described hemolytic reactions
Compatibility of transfused platelets
following the transfusion of ABO minor-incompatible plate-
The first data set was generated from a custom issue/return
lets.5,6 Nonetheless, ABOi platelet transfusions remain com-
product report from the LIS, which included all the blood
mon, and while the potential risks are generally recognized,
products issued by the blood bank, along with their final
the relative risk (or odds ratio) of transfusion reactions in
disposition (returned, transfused, wasted). The report also
the setting of ABOi platelet transfusions is unknown.1,7 The
provided each patient’s medical record number (MRN).
primary purpose of this study was to determine the rate of
This report indicated that 14,338 platelet units were trans-
transfusion reactions with ABOi platelet transfusions com-
fused during the study to 2826 unique patients. ABO blood
pared to ABO-compatible platelets and determine what
group types of the platelet unit and the patient were merged
types of reactions are observed with ABOi platelet transfu-
into the spreadsheet from two different sources. Patient
sions. Finally, the type of incompatibility was examined to
ABO types and date of birth were obtained via a report from
determine if this impacted the transfusion reaction rate
or not.

MATERIALS AND METHODS

Study overview
This retrospective study was approved by the institutional
review board (IRB 201811791) at our large academic medical
center, which encompasses a Level 1 trauma center, solid-
organ transplantation, hematopoietic stem cell transplanta-
tion, and a pediatric hospital with a neonatal intensive care
unit. Electronic medical records (EMRs; EPIC Systems Corpo-
ration) and blood bank laboratory information system (LIS;
Haemonetics) data at our institution were reviewed from
October 2015 (when the LIS was implemented) through
November 21, 2018. All platelets transfused during this
period were leukoreduced apheresis components, and anti-A
or anti-B titers were not performed. In May 2018, Verax
testing was implemented, and a small fraction of platelets
were issued on Day 6 or 7 after that date. Similar to other
institutions,1 ABO-compatible platelets are prioritized for
infants and ABO-identical units are the first choice for all
patients when inventory allows. The blood bank policy priori-
tizes giving ABO-identical platelets when other factors are
equivalent. This policy prioritizes giving antigen-incompatible
units (e.g., AB to A) versus plasma-incompatible units
(e.g., O to A). Despite this policy, ABOi platelets were com-
monly provided largely based on inventory and platelet expi- Fig. 1. Study design and data acquisition. This schematic
ration dates. All transfusion reactions reported to the blood summarizes how the ABO compatibility for all platelet
bank were systematically evaluated, and hard copies of the transfusions between October 2015 and November 2018 was
laboratory investigations were available for review. Electronic obtained and then merged with transfusion reaction data that
reports from the LIS and EMR were merged and used to allowed the determination of reaction rates for platelet
compile data on all platelet transfusions and all transfusion transfusions during this time frame.

2 TRANSFUSION

the EMR, which includes all ABO types reported during the
time of the study. Duplicates sharing both the same MRN
and same ABO type were removed, and then all MRNs with
one unique ABO type were merged into the platelet trans-
fused report. Patients with more than one unique ABO
blood type recorded during the study period were identi-
fied, most of whom had undergone an ABOi hematopoietic
stem cell transplant. Patients with more than one unique
ABO type were entered into the report manually, based on
their ABO type at the time of each transfusion. In a few
cases, platelets were transfused between dates when the
ABO type of the patient changed. In those instances, the
patient ABO type was listed as unknown for that transfusion,
and the ABO compatibility of the platelet transfusion was
also listed as unknown. Rarely, no ABO type was available
or performed (such as with emergency-released blood prod-
ucts), and the compatibility of these transfusions was also
listed as unknown. In all, just 19 of the 14,338 platelet trans-
fusions fell into this category of unknown compatibility.
None of these 19 transfusions were associated with a trans-
fusion reaction. The ABO types of the transfused platelet
units were obtained from a separate LIS report. These data
were exported into a spreadsheet and then merged with the
platelet transfusion data described above.
Compatibility of platelet transfusions can be classified
by a variety of schemes. For this study, we used the classifica-
tion scheme illustrated in Fig. 2. Only ABO-identical transfu-
sions were classified as compatible. Plasma-incompatible
transfusions were classified as minor incompatible, while
Fig. 2. Compatibility chart used for this study. This chart shows
how the 14,319 platelet transfusions between October 2015 and
November 2018 into patients with known ABO type at the time
of the transfusion were classified. Compatible (Comp) is defined
as ABO identical. Major incompatible (Major) includes
transfusion where the product contains A or B antigens not
found in the patient. Minor incompatible (Minor) includes
transfusions where the product contains anti-A or anti-B
antibodies that are incompatible with the patient’s ABO type.
Bidirectional (Bidir) means the transfusion contains both
incompatible antigens and incompatible antibodies.
TRANSFUSION REACTIONS WITH ABOI PLATELETS
A/B antigen-incompatible transfusions were classified as
major incompatible. Transfusions that were incompatible for
both plasma and A/B antigens were classified as bidirectional
incompatible (A into B or B into A).
Transfusion reactions
The other major data set used in this study included all
suspected transfusion reactions reported to the blood bank dur-
ing the study period. Per protocol at our institution, when a
suspected transfusion reaction is ordered, a patient blood sam-
ple is drawn and sent to the blood bank to repeat ABO-Rh
blood typing and perform a direct antiglobulin test. A posttrans-
fusion specimen of the patient’s plasma is also examined for
evidence of hemolysis. Suspected transfusion reactions are clas-
sified by physicians on the transfusion medicine service follow-
ing the Centers for Disease Control and Prevention (CDC) and
National Healthcare Safety Network (NHSN) guidelines for clas-
sification of transfusion reactions.8 These results were manually
entered into a spreadsheet from paper files maintained in the
blood bank for every reaction. A total of 476 transfusion reac-
tions were reported during the study period, 165 of which
involved a single platelet transfusion. Twelve of the 476 transfu-
sion reactions involved multiple blood products, including at
least one platelet transfusion. A review of those reactions by
two of the authors (CMK and NM) clearly implicated a single
platelet product in 3 of the 12 transfusions. In total, 168 transfu-
sion reactions were attributed to platelet transfusions in
132 unique patients, and 167 of these reactions were to subjects
greater than 1 year of age and were included in the analysis.
These transfusion reactions were categorized as follows: acute
hemolytic (AHTR; N = 3), allergic (N = 72), febrile nonhemolytic
(FNHTR; N = 51), transfusion-associated circulatory overload
(TACO; N = 1), transfusion-associated dyspnea (TAD; N = 4),
transfusion-related acute lung injury (TRALI; N = 1). A total of
35 reactions did not meet criteria for a specific transfusion reac-
tion as defined by the CDC/NHSN guidelines and were classi-
fied as unknown/unrelated. Reactions were not routinely
graded for severity, and this information was not included in
the initial data acquisition. As allergic reactions are often clini-
cally mild and the CDC/NHSN has stopped tracking minor
allergic reactions, the severity of allergic reactions was deter-
mined by one of the authors (CMK). Reactions were deter-
mined to be severe following CDC/NHSN criteria, and severe
reactions generally involved symptoms of laryngeal edema, dys-
pnea, or oxygen desaturation. A total of 18.1% of the allergic
reactions were classified as severe.
Platelet unit age
The expiration date of the transfused platelet units was
obtained from the LIS report, which also included ABO type.
This date was used to calculate the age of the unit at the time
it was issued from the blood bank based on a 5-day expiration
date for nearly all platelets transfused during this time. For
units that had a modified expiration date due to preparation
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MALVIK ET AL.

of aliquots from the unit, washing, or rapid bacterial testing,
the age of the unit was calculated using the collection date of
the unit that was available within the LIS.
Statistical analysis
We estimated that about 33% of platelet transfusions would
be ABOi and that transfusion reaction rates would be about
1%. Using a power calculator for dichotomous endpoints, we
estimated that we would need to review at least 5000 platelet
transfusions to detect an increase in transfusion reaction
rates to 2%. However, we designed the study to be as large as
possible in the time frame indicated to allow detection of rel-
atively modest changes in reaction rates and allow for subset
analysis based on specific type of incompatibility and type of
reaction. Transfusion reaction rates for the compatible versus
the ABOi transfusions were compared using the chi-square
test.9 This test compares the “expected” number of events
for that group to the actual number of events observed. This
test was only applied when the “expected” number of events
for each group was at least five.10 The transfusion reaction
rate for the compatible platelet transfusions was used to
determine the expected number of events within each
group. P values less than 0.05 were considered statistically
significant. Univariate logistic regression analysis was con-
ducted to determine the odds ratio (and 95% confidence
interval) for transfusion reactions, CDC/NHSN qualifying
reactions, FNHTRs and allergic reactions with platelet trans-
fusion compatibility, patient age, patient ABO type, unit
ABO type, and sex. These analyses were performed with
computer software (SAS, version 9.4, SAS Institute). If the
95% confidence interval did not overlap with 1.0, the results
were considered statistically significant.
RESULTS
Platelet transfusion compatibility rates
During the study period, 13,447 platelet transfusions to
patients greater than 1 year of age could be classified for

Fig. 3. Reaction rates for ABO compatible (Comp) and ABO-incompatible (ABOi) transfusions. The reaction rate for all transfusion
reactions reported to the blood bank (A), for those reactions that met CDC/NHSN criteria (B), for those that met criteria for a FNHTR
(C), or an allergic reaction (D) are shown. For each of these analyses, the number of observed reactions for the ABOi group was
significantly higher (p < 0.001) than the number of reactions observed for the compatible group.

4 TRANSFUSION
 TRANSFUSION REACTIONS WITH ABOI PLATELETS

ABO compatibility. Of these, 61.7% of platelet transfusions

were compatible (ABO identical), 19.7% were major incom-
patible, 14.1% were minor incompatible, and 4.5% were
bidirectional incompatible. These results are similar to
reported rates at other institutions.1,2 When compatibility
rates were evaluated by patient blood type, blood type A
and type O patients were much more likely to receive com-
patible platelets, compared to B or AB patients (data not
shown). Reaction rate for females (1.20%) was not statisti-
cally different than that observed for males (1.27%).

Transfusion reaction rates for ABO compatible

versus ABOi platelets
The 167 transfusion reactions included in the study resulted in
an overall reaction rate of 1.24%. This includes all reactions
reported to the blood bank, including those that would be
classified as unrelated or “unknown” by CDC/NHSN defini-
tions.8 This reaction rate is similar to those reported by others,
and the rates of allergic reactions (0.53%) or FNHTRs (0.38%)
are consistent with US hemovigilance reports.11 Hemolytic
reactions (0.02%) and respiratory reactions (TACO, TRALI,
TAD; 0.04%) were also observed. Suspected reactions that did
not meet CDC/NHSN criteria were classified as unknown/
unrelated and occurred at a rate of 0.26%.
Transfusion reaction rates were determined based on the
compatibility of the platelet transfusion. Patients who received
compatible platelet transfusions had the lowest rate of transfu-
sion reactions. This was true whether all reactions were
included, when only reactions that met CDC/NHSN criteria
were included, or when just FNHTRs or allergic reactions were
examined (Fig. 3). As allergic reactions are often mild, we
graded these reactions for severity using CDC/NHSN criteria.
Of note, the allergic reactions with ABOi platelets were signifi-
cantly more likely to be classified as severe (26.3%) compared
to ABO-compatible allergic reactions (8.8% severe; p < 0.01).

Unit age and reaction rate
One potential explanation for the higher reaction rates
observed in ABOi platelet transfusions may be that these
transfusions are more likely to be older units that are closer
to the 5-day expiration of the product. This is the point at
which the blood bank must decide whether to risk outdating
a 5-day platelet by issuing a younger ABO-compatible platelet
to a patient. Thus, we analyzed whether unit age could
account for the increased reaction rates in ABOi platelets. As
expected, most units issued to the subjects studied were
issued on Day 3, 4, or 5, with more than 96% of the units
issued to patients in this window (Fig. 4A). The percentage of
compatible units decreased slightly as age of the units
increased, going from 69% on Day 3 to 58% on Day 5 (Fig. 4B).
Because so few platelets were issued before or after these
time points, only reaction rates for platelets issued on Days
3 to 5 were calculated. While overall reaction rates did
increase with unit age, ABOi platelets consistently had a
Fig. 4. Increased reaction rates with ABOi platelets is
independent of platelet unit age at time of issue. (A) The
number of units transfused versus unit age. (B) The percentage
of ABO-compatible units transfused versus unit age.
(C) Transfusion reaction rates versus unit age between 3 and
5 days is shown for all units (middle line), compatible units
(bottom line), and ABOi units (top line). The reaction rates for
platelets transfused on Day 1 (13), Day 2 (304), Day 6 (136) and
Day 7 (28) are not shown due to the small number of
transfusions on those dates. The reaction rates for all platelets
on Days 3-5 were compared using the chi-square test and Day
3 versus Day 4 (P = 0.009), Day 3 versus Day 5 (p = 0.002), and
Day 4 versus Day 5 (p = 0.011) were all significantly different.
higher reaction rate than ABO compatible platelets at each
time point analyzed (Fig. 4C). Chi-square analysis for the
platelets transfused on Day 5 showed that reaction rates for

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MALVIK ET AL.

Fig. 5. Reaction rates for ABO-compatible (Comp), major incompatible (Major), minor-incompatible (Minor), and bidirectional-
incompatible (Bidir) platelet transfusions. (A) Reaction rates for all reactions reported to the blood bank are shown for each type of
transfusion. (B) Reaction rates for reactions that met CDC/NHSN criteria are shown for each type of transfusion. (C) Reaction rates that
met criteria for FNHTRs are shown for each type of transfusion. (D) Reaction rates that met criteria for allergic transfusion reactions are
shown for each type of transfusion. Statistical analysis for these data is summarized in Table 1.

ABOi platelets were significantly different than for compatible
platelets (p < 0.0001). These results demonstrate that transfu-
sion reaction rates are independently affected by platelet unit
age and by ABO incompatibility.
Hemolytic reactions
We also determined the rates of specific types of transfusion
reactions in the different compatibility categories. While only
three acute hemolytic reactions were observed, two of these
occurred with minor-incompatible transfusions (type O plate-
lets into type AB and type B patients), and one occurred in a
bidirectional-incompatible transfusion (type B platelet into
type A patient). Thus, the overall rate of hemolytic transfusion
reactions from plasma-incompatible platelet units was 3 in
2522 transfusions (or about 1 in 840 transfusions; 0.12%). No
hemolytic reactions were observed in compatible or major-
incompatible transfusions.
Transfusion reaction rates based on type of
incompatibility
To complete our analysis, the transfusion reaction rates
were determined based on the type of incompatibility of the
platelet transfusion. We found that all three categories of
ABOi platelet transfusions had higher reaction rates than
seen with compatible platelet transfusions. This was true
when either all reactions or only CDC/NHSN classifiable
reactions were considered (Fig. 5A,B). These results suggest
that plasma-incompatible as well as antigen-incompatible
transfusions may contribute to the increased rates seen with
ABOi platelets. When specific reaction types were consid-
ered, we found that both FNHTRs and allergic reactions
were more commonly seen with all incompatible subgroups
as well (Fig. 5C,D). To determine if any of these differences
were statistically significant, univariate logistic regression
analysis was conducted to determine the odds ratio (and
95% confidence interval) for transfusion reaction rates with
major-, minor-, and bidirectional-incompatible platelet
transfusions compared to the rates with compatible platelet
transfusions (Table 1). These data show that ABOi platelets
as a group, as well as the major-incompatible platelet trans-
fusion subgroup, had statistically significant increased
chances of being associated with transfusion reactions com-
pared to ABO-compatible platelets. These significant differ-
ences with major-incompatible transfusions (N = 2651) held
true when CDC/NHSN qualifying reaction, FNHTR, and

6 TRANSFUSION
 TRANSFUSION REACTIONS WITH ABOI PLATELETS

A single-institution cohort study described a reduction

TABLE 1. Odds ratios and 95% confidence intervals in transfusion reactions following implementation of a pol-
for different transfusion reaction types relative to
reaction rates for ABO compatible platelet icy that provided either ABO-identical platelets or minor-
transfusions incompatible platelets that had been washed to remove
Odds ratio 95% confidence interval p value ABO antibodies from the platelet unit.12 However, the trans-
All reported reactions fusion reaction rates at this institution were quite low even
All ABOi 1.81 1.33-2.46 <0.001 before implementation of the policy (<1 in 1000). This pol-
Bidirectional 1.74 0.90-3.38 0.101
Major 2.16 1.53-3.07 <0.001 icy also resulted in a slight increase in product wastage of
Minor 1.34 0.85-2.12 0.214 about 5%. An overall reaction rate of 1.24% was observed in
CDC/NHSN qualifying reactions the present study, which is closer to usual reported reaction
All ABOi 2.01 1.42-2.84 <0.001
Bidir 1.63 0.79-3.58 0.225 rates.11
Major 2.41 1.63-3.56 <0.001 Multiple authors have suggested that large randomized
Minor 1.57 0.95-2.59 0.078 controlled studies are necessary to determine if ABOi plate-
FNHTR
All ABOi 2.31 1.32-4.04 0.003 lets increase transfusion reaction rates.3,7 This study was not
Bidirectional 1.30 0.30-5.57 0.721 randomized or blinded, so it is possible that reporting bias of
Major 3.00 1.62-5.54 <0.001 providers could partially explain the results. Transfusing staff
Minor 1.68 0.74-3.79 0.215
Allergic reactions (typically nurses) could be aware that the products are not
All ABOi 1.81 1.14-2.88 0.012 ABO identical, which could lead to increased reporting for
Bidirectional 1.61 0.57-4.56 0.368 these patients. However, this seems unlikely to completely
Major 2.13 1.25-3.62 0.005
Minor 1.42 0.72-2.81 0.310 explain the results as most providers/nurses are unlikely to
ABOi = ABO-incompatible; CDC = Centers for Disease Control be aware that the compatibility of platelets may influence
and Prevention; FNHTR = febrile nonhemolytic transfusion reac- reaction rates. In our experience, no transfusing providers
tion; NHSN = National Healthcare Safety Network. have been concerned about the ABO compatibility of a plate-
let transfusion as a possible cause of a reaction. Furthermore,
we found that the differences were maintained even when
reactions not meeting CDC/NHSN criteria were excluded.
allergic reaction rates were examined (Table 1). While bidi- The data in this and other studies suggest that a randomized
rectional (N = 607) and minor-incompatible (N = 1890) controlled trial with patients randomized to receive ABOi
transfusions had higher rates of reactions, none of these platelets may not be necessary and could in fact be con-
subgroups reached statistical significance when compared to traindicated or unethical.
ABO-compatible transfusions. The lack of statistical signifi- Most policies related to incompatible platelets have
cance could be due to the smaller number of transfusions in focused on plasma (minor) incompatibility. This likely is due
these groups, though it is of interest that major-incompatible to the rare but lethal consequences of giving plasma-
transfusions had the highest reaction rates of any of the incompatible platelets.5,6 Less attention has been given to
groups in this series. Univariate analysis was also performed A/B antigen (major)-incompatible platelet transfusions. This
for patient age (<18 vs. adult), patient ABO type (type O as study found that major-incompatible platelet transfusions
reference), unit ABO type (type AB as reference) and sex, but had statistically significantly higher rates of total reported
none of these analyses showed significant differences reactions, reactions meeting NHSN definitions, allergic reac-
between the groups (data not shown). tions, and FNHTRs. These robust findings support the con-
clusion that A/B antigens in the platelet product contribute
to patient signs or symptoms that result in the reporting of a
transfusion reaction. The mechanism of these reactions is
DISCUSSION
not addressed in this study, but others have shown that cir-
The relationship between transfusion reaction rates and culating immune complexes have been shown to occur fol-
ABOi platelet transfusions has not been well established. A lowing transfusion of ABOi platelets.13 These complexes may
comprehensive systematic review from 2009 looked at be the cause of the increased allergic reaction and/or FNHTR
77 studies that included more than 1500 patients and con- rates observed with major-incompatible transfusions.
cluded that ABOi platelets could not be associated with Allergic reactions are commonly observed with platelet
increased transfusion reaction rates.3 However, none of the transfusions, and these were the most frequent reaction types
studies reviewed were powered to detect even modest observed in this study. Importantly, allergic reaction rates
increases in transfusion reaction rates. The current study, also appeared to differ depending on the compatibility of the
evaluating over 13,000 platelet transfusions in 2547 unique transfusion, with ABO major-incompatible platelets leading
patients and the resultant 167 transfusion reactions, is the to the highest proportion of allergic transfusion reactions.
largest single study to date that evaluates the impact of ABO Furthermore, 26% of the allergic reactions associated with
incompatibility on transfusion reaction rate. ABOi platelet transfusions in this study were classified as

TRANSFUSION 7
MALVIK ET AL.
severe. Of note, one recent study examined allergic reactions
and found that 61% of products are not completed following
an allergic reaction, and for platelets this results in an aver-
age of 138.4 mL of the product not being transfused.14
FNHTRs are also commonly reported during platelet transfu-
sions, and this was the second most frequent type of transfu-
sion reaction reported during our study period. The odds
ratios for ABO major-incompatible platelet transfusions were
approximately double that for compatible transfusions for
both FNHTRs and allergic transfusion reactions.
This study suggests that efforts to maximize the num-
ber of ABO-compatible/identical platelet transfusions that
are provided to patients could significantly reduce the rate
of transfusion reactions. One approach to maximizing the
percentage of compatible units could be to perform rapid
bacterial testing to increase the product shelf life up to
7 days.15 This would allow additional time to provide ABO-
identical platelets to patients. However, this approach would
likely result in more platelets being transfused beyond the
typical 5-day expiration date. Since we found that reaction
rates went up with unit age (Fig. 4C), the benefits of
increasing the proportion of ABO-compatible transfusions
could be offset by the increased risk associated with transfu-
sion of older platelet units. With the recent FDA guidance
documents providing for longer platelet shelf life, it will be
important to monitor transfusion reaction rates with these
older products.
The data in this study may be useful in developing
policies that reduce transfusion reactions while preserv-
ing platelet inventories. Finding a standarized approach
for all situations and patients is unlikely to be easy and
likely to solicit a wide range of opinions on how to miti-
gate these increased risks of ABOi platelet reactions.
Regardless of how one views these findings, this quantita-
tive analysis should be useful in developing processes
that minimize platelet wastage while maximizing patient
safety for individual institutions. At our institution, we are
considering prioritizing ABO-identical platelets for those
most likely to have reactions. This might include patients
requiring chronic transfusions such as leukemia or stem
cell transplant patients. These patients could be identified
by the blood bank based on need for irradiated blood
products, which are generally recommended for these
patients.
In summary, this single-institution study looking at
reaction rates for more than 13,000 platelet transfusions
found that ABOi platelets have a 1.5- to 2.0-fold increase in
the likelihood of being associated with a transfusion reac-
tion. This increased risk appeared to be independent of unit
age and was observed for all reactions reported to the blood
bank, only those meeting CDC/NHSN criteria, FNHTRs, and
allergic reactions. The finding that major-incompatible units
had the highest reaction rates among a variety of types sug-
gests that circulating immune complexes involving patient
anti-A or anti-B antibodies combined with A or B antigens
8 TRANSFUSION
from the transfused units may be an underappreciated
cause of a variety of platelet transfusion reactions.
ACKNOWLEDGMENTS
The authors thank Hannah Born for secretarial assistance with the
manuscript. The statistical analysis for this study was supported in
part by the University of Iowa Clinical and Translational Science
Award, granted with funds from the National Institutes of Health
(UL1TR002537).
CONFLICT OF INTEREST
The authors have disclosed no conflicts of interest.
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