REVIEW
ABO-identical versus nonidentical platelet transfusion:
a systematic review
Nadine Shehata, Alan Tinmouth, Gary Naglie, John Freedman, and Kumanan Wilson
BACKGROUND: The significance of ABO matching for
platelet (PLT) transfusion has not been clearly defined.
The primary objective of this report is to assess
whether ABO-identical PLT transfusion is associated
with improved mortality and/or morbidity for patients
with hematologic/oncologic disorders.
STUDY DESIGN AND METHODS: A systematic review
to January 2009 was conducted. Data on mortality,
morbidity, PLT refractoriness, and PLT increment after
transfusion were abstracted.
RESULTS: A total of 100 citations were identified. Nine-
teen studies were included in the systematic review. A
total of 1502 patients from three randomized controlled
trials and 16 observational studies were included. Sur-
vival, bleeding events, and transfusion reactions were
only considered as secondary outcomes in the reports
reviewed. The PLT count increment was the primary
outcome of several studies and was consistently higher
with ABO-identical PLT transfusion. The largest differ-
ence in increment between ABO-identical and noniden-
tical PLT transfusion was 4 ¥ 109/L. No consistent
benefit in clinical outcomes was noted. Survival was
assessed in three reports with conflicting results.
Although two studies described bleeding as an
outcome, the assessment of hemorrhage was consid-
ered inadequate. In six studies, ABO-nonidentical PLT
transfusion was not associated with transfusion reac-
tions, and the results from four studies addressing the
impact of ABO-identical PLT transfusion on PLT and red
blood cell utilization were conflicting.
CONCLUSION: ABO-identical PLT transfusion results
in a higher PLT increment. Randomized controlled trials
are required to definitely determine the effect of ABO-
identical PLT transfusion on survival, bleeding events,
or transfusion reactions.
2442 TRANSFUSION Volume 49, November 2009
_02273 2442..2453
T
ransfusion specialists have debated the signifi-
cance of the ABO blood group in platelet (PLT)
transfusion for more than 50 years.1 Although it
is well established that after transfusion of ABO-
incompatible PLTs, anti-A and anti-B can cause incidents
of intravascular hemolysis, it is not definitively known
whether ABO matching of PLT transfusion improves
other outcomes. Providing ABO-identical PLTs can be pro-
blematic because only limited inventories are available.
Also, there is the wastage of PLTs that are not ABO identi-
cal, and if patients require HLA-matched PLTs for refrac-
tory thrombocytopenia, these PLTs may not be ABO
identical.2 In addition, periodic shortages of PLT products
From the Department of Medicine, University of Toronto, Divi-
sion of Hematology, St Michael’s Hospital, Canadian Blood Ser-
vices, Toronto, Ontario; the University of Ottawa Centre for
Transfusion Research, Clinical Epidemiology Program, Ottawa
Health Research Institute, Department of Medicine, the Ottawa
Hospital, University of Ottawa, Canadian Blood Services,
Ottawa, Ontario; the Departments of Medicine and Health
Policy, Management and Evaluation, University of Toronto, Divi-
sion of General Internal Medicine, University Health Network,
Geriatrics Program, Toronto Rehabilitation Institute, Toronto,
Ontario; and the Departments of Pathology, University of
Toronto, Li Ka Shing Knowledge Institute, Toronto, Ontario,
Canada.
Address reprint requests to: Nadine Shehata, MD, Queen
Wing, 2-065c, St Michael’s Hospital, 30 Bond Street, Toronto,
ON M5B 1W8, Canada; e-mail:shehatan@smh.toronto.on.ca.
GN is supported by the Mary Trimmer Chair in Geriatric
Medicine Research, University of Toronto. KW is supported by
the Canada Research Chair in public health policy.
Each author contributed to the design and conduct of the
work, NS conducted the systematic review and prepared the
manuscript, NS and AT reviewed the citations and validated
data abstraction, and all authors have contributed to the writing
and revision of the manuscript.
Received for publication September 26, 2008; revision
received April 14, 2009, and accepted April 17, 2009.
doi: 10.1111/j.1537-2995.2009.02273.x
TRANSFUSION 2009;49:2442-2453.

put additional strain on the blood service and the blood
transfusion specialists when providing ABO-matched
products. A recent survey of 3152 North American labora-
tories found that 17% of transfusion medicine laboratories
do not have a policy regarding the use of ABO-
nonidentical PLTs.2 Thirty percent of institutions that had
a policy provided ABO-incompatible PLT or plasma prod-
ucts if there was an urgent need for PLT products, and 50%
indicated that ABO-incompatible PLTs or plasma would
be provided if ABO-compatible products are not avail-
able.2 Therefore, determining the clinical value of trans-
fusing ABO-identical PLTs is essential.
We conducted a systematic review of the literature
to determine whether the transfusion of ABO-identical
PLTs improves outcomes in patients with hematologic/
oncologic disorders, including patients undergoing
hematopoietic stem cell and bone marrow transplantation
(BMT), compared to ABO-nonidentical (i.e., plasma- or
PLT-incompatible) PLT transfusion.The primary outcomes
that we considered were mortality and morbidity (i.e.,
bleeding and transfusion reactions). We considered PLT
refractoriness, the posttransfusion increase in PLT count,
and changes in PLT utilization as secondary outcomes.
MATERIALS AND METHODS
Identification and selection of studies
We conducted a systematic search of the MEDLINE (1950
to Week 2 November 2007) and HEALTHSTAR (1966 to
November 2007) databases. The search was updated to
January 2009. We used the following medical subject
heading or text words to search the databases: “ABO
blood-group system,” “blood grouping and crossmatch-
ing,” “ABO matching,” “ABO identical,” “ABO unmatched,”
“blood group antigens,” “platelet transfusion,” “platelet
refractoriness,” “platelet count,” and “platelet increment.”
The full search strategy is provided in the Appendix. We
also conducted a bibliographic search to ensure that all
relevant publications were included.
We included a study in the systematic review if it met
the following criteria: 1) it was published in English; 2) it
was an original report; and 3) one of the primary out-
comes was morbidity, mortality, refractoriness, or PLT
increment. We excluded studies based on the following
criteria: 1) they were case reports, letters, or abstracts or 2)
the objective was not to analyze ABO-incompatible
transfusion.
Data extraction and analysis
Two reviewers (NS, AT) independently assessed the
MEDLINE and HEALTHSTAR abstracts for inclusion/
exclusion criteria. When a discrepancy occurred between
the reviewers, a third reviewer (KW) assessed the abstract
and/or the full publication was retrieved and a decision
was arrived at by consensus.
ABO-MATCHED PLATELET TRANSFUSION
The data were abstracted by one reviewer (NS) and
verified by a second author (AT). We abstracted study
characteristics using standardized data abstraction forms.
We abstracted information on the following study
characteristics: the year of study, country where the study
took place, whether the study was single or multicentered,
setting, characteristics of participants, inclusion/
exclusion criteria, study design, sampling methods,
sample size, the dose of PLTs transfused, the PLT product
transfused (e.g., random donor, single donor), the use of
leukoreduction, the duration of PLT storage, the method
to determine the PLT increment, the time to determine the
PLT increment after transfusion, the transfusion criteria,
and the definition of PLT refractoriness. We evaluated the
quality of the randomized controlled trials by examining
the randomization technique, the mechanism for con-
cealment of allocation, whether the study was blinded,
whether the groups were comparable at baseline, the
primary outcomes assessed, the use of an intention-to-
treat analysis, and the extent of losses to follow-up. The
quality of the observational studies was evaluated by
examining the method of data collection, the sampling
methods, the outcomes assessed, and the statistical
analysis methods.
We also extracted information on the PLT transfusion
criteria, survival, hemorrhage, transfusion reactions, the
frequency of PLT refractoriness, PLT and red blood cell
(RBC) utilization, and the PLT increments associated with
ABO-identical and ABO-nonidentical transfusion. We
did not conduct a meta-analysis since the study designs
and reporting of outcomes were too heterogeneous to
combine.
Definitions for ABO-matched transfusions
Because there were various definitions for ABO matched
transfusions, we defined 1) ABO-identical PLT transfusion
as both the donor and the recipient being the same ABO
type, 2) ABO-compatible PLT transfusion when the donor
PLTs do not carry A or B antigens that are incompatible
with the recipient’s plasma (i.e., PLTs from an O donor to
an A, B, or AB recipient or PLTs from an A or B donor to an
AB recipient), 3) ABO-incompatible PLT transfusion (i.e.,
all other PLT transfusions), and 4) ABO-nonidentical
PLT transfusion to reflect ABO-compatible and ABO-
incompatible PLT transfusion. If there was insufficient
information to classify the PLT transfusion, the classifica-
tion used by the investigators was used.
RESULTS
Results of the literature search
We retrieved a total of 77 citations from MEDLINE and 23
from HEALTHSTAR. Twenty-three studies fulfilled the
Volume 49, November 2009 TRANSFUSION 2443
SHEHATA ET AL.

inclusion criteria. Five studies were excluded for the fol-

<15 ¥ 109-20 ¥ 109/L, before minor surgical

lowing reasons: 1) all patients in one study were adminis-
tered ABO-identical PLTs,3 2) two studies did not consider

Prespecified transfusion criteria

procedures and in the presence of

ABO blood groups in their analyses,4,5 3) one study only
assessed changes in the hemoglobin (Hb) concentration
with ABO-incompatible plasma,6 and 4) one study did
not specify what outcomes were being assessed.7 Two

coagulation disorders
additional studies were identified when the search was
updated.8,9 Twenty studies were included in this system-
atic review.

<20 ¥ 109/mL

Not reported

‡ Patients did not have high fever (>38.3°C), splenomegaly, coagulation abnormalities, or active bleeding. Patients with AB blood group were excluded.
Characteristics of the studies
Randomized controlled trials

PLT product
One study indicated that recipients of PLT transfusions

PRD†

PRD§
PRD
were paired randomly; however, we did not classify this
study as a randomized controlled trial because recipients

TABLE 1. Characteristics of the randomized controlled studies

were not randomly assigned to receive ABO-identical
PLTs. They were randomly assigned to receive PLTs from

Method to determine
divided apheresis units.10 Thus, three of the studies

PLT increment
included in our final analysis were randomized controlled

* CCI = posttransfusion - pretransfusion PLT count (¥109)/L ¥ body surface area (m2)/number of PLTs infused (¥1011).
CCI*

CCI

CCI
trials (Table 1).11-14 Two publications described the same
study, so for the purposes of this systematic review they
were considered as one study.11,12 One of the randomized
controlled trials used a crossover design.14 Two trials were
conducted in the United States and one in the United

relapsed Hodgkin’s lymphoma

Kingdom. The patients included were those with hemato-
logic malignancies. All studies included newly diagnosed
Hematologic malignancies

Acute leukemia, ASCT for

Patient population

patients.11,13,14 One study included patients who did not

have clinical factors known to be associated with PLT
consumption (e.g., infection splenomegaly).14 In one

ASCT = autologous stem cell transplant; PRD = pooled random-donor PLT product.
Acute leukemia‡
study, leukoreduced PLT products were only used after
febrile reactions.11 The PLT increment was measured using
the corrected count increment (CCI),11,13,14 and PLT trans-
fusion triggers, where reported, were below 20 ¥ 109/L.11,13
The primary outcomes as defined by investigators were
the PLT increment11,14 or efficacy and consequence of
Center status
Single center

Single center

Single center

administering ABO-mismatched PLTs.13

Prospective and retrospective studies

§ Each transfusion consisted of 8 units of PLTs.
† PLTs only leukoreduced for febrile reactions.

Our final analysis included five prospective8-10,15,16 and 11

retrospective studies (Table 2).17-27 We classified one study
United Kingdom
United States

United States

as a prospective study although it was likely a retrospec-

Country

tive analysis of prospectively collected data.9 Of these, 10

were conducted in the United States,10,16,18,20,21,23-27 two in
Switzerland,8,9 and one each in Italy,15 Egypt,17 France,19
and Sweden.22 Two studies were multicentered,5,18 and the
remainder were single-centered. The PLT products trans-
Heal, 1993, 199411,12

fused included single-donor apheresis PLTs8-10,15,17,22-24 or a

First author, year

combination of single-donor and pooled random-donor

Carr, 199013

Lee, 198914

PLTs; one report did not describe the type of PLT product
transfused.16 The patient populations were heteroge-
neous, including individuals with hematologic malignan-
cies,8,9,15,17,18,23,24,26,27 solid tumors,8,9,17,19,23,26 idiopathic

2444 TRANSFUSION Volume 49, November 2009

 TABLE 2. Characteristics of prospective and retrospective studies
First author, Definition of PLT Prespecified transfusion
year Country Center status Patient population refractoriness PLT product criteria
Prospective
Julmy, 20098 Switzerland Single center Pediatric patients with hematologic Not an endpoint SDA <10 ¥ 109/L or bleeding
malignancies, solid tumors, aplastic
anemia without fever/splenomegaly
Heim, 20089 Switzerland Single center Adult and pediatric patients with malignant Not an endpoint Irradiated SDA 10 ¥ 109-20 ¥ 109/L
or nonmalignant hematologic diseases,
nonhematologic malignancies, HSCT
Jimenez, 200310 United States Single center Hematologic malignancies* Percentage of PLT SDA‡ 10 ¥ 109-20 ¥ 109/L
recovery†
Balduini, 200115 Italy Single center Pediatric allogeneic HSCT recipients Not an endpoint Mainly SDA PRD if SDA not <20 ¥ 109/L or bleeding
available
Aster, 196516 United States Single center Healthy volunteers and convalescent Not an endpoint Not reported No criteria to receive
patients who did not have PLTs
hematologic/liver disease or splenic
enlargement
Retrospective
Blumberg, 200827 United States Single center Acute leukemia Not an endpoint Predominately PRD PLTs, ⫾ <20 ¥ 109/L
leukoreduction ⫾ washed
Aboul Enein, Egypt Single center Hematologic malignancy, ITP, renal failure, Difference between pre- and Leukoreduced SDA§ Not reported
200717 metastatic disease posttransfusion counts
Slichter, 200518 United States Multicenter Acute myeloid leukemia Posttransfusion PLT PRD, FPRD, UVBRDP, <20 ¥ 109/L or higher for
increment <11 ¥ 109/L FRDA bleeding or surgery
Lapierre, 200519 France Single center Pediatric HSCT recipients with Not an endpoint PRD or SDA <20 ¥ 109/L for
neuroblastoma or brain tumors who neuroblastoma or
received busulfan <50 ¥ 109/L for brain
tumor recipients or for
bleeding
Klumpp, 199620 United States Single center Autologous/allogeneic marrow and SCT Three consecutive Leukoreduced PRD or SDA <20 ¥ 109/L or
recipients CCIs < 7500 >30 ¥ 109-50 ¥ 109/L
when bleeding
Heal, 199421 United States Single center Autologous marrow transplant recipients Not an endpoint PRD or SDA <20 ¥ 109/L
with lymphoma
Shanwell, 199122 Sweden Single center Allogeneic marrow transplant recipients Not an endpoint Irradiated SDA <30 ¥ 109/L
Heal, 198723 United States Single center Hematologic/oncologic malignancy, CCI < 7500 SDA, HLA-A,B matched Not reported
autologous/allogeneic BMT refractory to
PLT transfusions
Duquesnoy, United States Single center Aplastic anemia, leukoproliferative disease Percentage of PLT SDA Not reported
197924 refractory to PLT transfusions recovery†
Tosato, 197825 United States Single center Aplastic anemia refractory to PLT Three consecutive PRD and SDA Not reported

Volume 49, November 2009

transfusions CCIs < 2500
Van Eys, 197826 United States Single center Pediatric leukemia and solid tumors <20 ¥ 109/L PRD and SDA <50 ¥ 109/L, hemorrhage
or for surgery
* Patients were ambulatory and did not have severe infection, fever, hypotension, or bleeding.
† Percentage of PLT recovery = posttransfusion - pretransfusion PLT count (¥109)/L) ¥ 1.05 ¥ weight (kg)/1011 PLTs transfused.
‡ PLTs from one donor were administered to randomly paired recipients.
§ The investigators also included apheresis PLTs from directed/designated donors.
CCI = posttransfusion - pretransfusion PLT count (¥109)/L ¥ body surface area (m2)/number of PLTs infused (¥1011); FRDA = filtered random-donor apheresis PLT concentrate; FPRD = filtered
pooled random-donor PLT concentrate; HSCT = hematopoietic stem cell transplant; ITP = idiopathic thrombocytopenic purpura; PRD = pooled random-donor PLT concentrate;
PSCT = peripheral stem cell transplant; SCT = stem cell transplant; SDA = single-donor apheresis PLT concentrate; UVBRDP = ultraviolet B-irradiated random-donor PLT concentrate.
ABO-MATCHED PLATELET TRANSFUSION

TRANSFUSION 2445
SHEHATA ET AL.

thrombocytopenic purpura,17 aplastic anemia,8,24,25 and

PLT increment after four

autologous9,20,21,23 and allogeneic transplantation;9,15,20,22,23

Primary outcome
individuals who were refractory to PLT transfusions;23-25

PLT transfusions
PLT refractoriness
healthy or convalescent medical patients;16 and hemato-

PLT increment
logic patients without fever, sepsis, or splenomegaly.10,24
Two studies excluded patients who did not have post-
transfusion PLT counts.20,26 One study excluded 15% of
PLT transfusions because of incomplete data.9 PLT
refractoriness was described as an outcome in seven

1 PRD/10 kg
studies, with various definitions for refractoriness used

PLT dose
(Table 2).17,18,20,23-26 The criteria for PLT transfusion was

3 ¥ 1011
8 PRD
generally a PLT count of less than 20 ¥ 109/L.8-10,15,18-22,27
The reported primary outcomes by the investigators
were the PLT increment using PLTs from the same apher-

follow-up
esis donor,10 the effect of PLT transfusion on survival,27 the

Loss of

Yes†
NR
NR
effect of ABO and other factors on PLT increment,9,15-18,25
the incidence of hepatic venoocclusive disease associated
with ABO-identical PLT transfusion,19 the effect of factors

Intent to treat

* Sixty percent of women in the ABO-identical group and four or more pregnancies compared to 10% in the incompatible group.
on PLT transfusion refractoriness,20 the impact of leukore-

yes or no
analysis,
TABLE 3. The quality of randomized controlled trials
duced ABO-identical PLT transfusion on morbidity and

No
No
No

† Seventy-five transfusions were excluded from the analysis, 10 patients were excluded from the analysis of refractoriness.
mortality,21 and the effect of ABO compatibility.8,22-24 One
report did not indicate a specific primary outcome.26
Survival, bleeding events, and PLT refractoriness were

yes or no
Blinding,
not reported in any of the prospective studies. The

No
No
No
number of days with hemorrhage was reported in one

NA = not applicable; NR = not reported; PRD = pooled random donor; RCT = randomized controlled trial.
retrospective report,21 and the frequency of hemolysis in
another observational study.22
Concealment of
allocation
Yes
No
No
Quality of studies
Randomized controlled trials
Of the three randomized controlled trials, two described
the randomization technique,11,13 only one report indi-
Comparable

‡ More females were allocated to the group receiving ABO-identical PLTs.

groups

cated whether allocation of treatment was concealed,11

Yes*
No‡
NA

and two studies described the characteristics of the

groups to determine whether the groups were comparable
(Table 3).11,13 The PLT dose was described in two studies
Crossover, technique not specified

(Table 3).11,13
Randomization technique

Random number generation

Prospective and retrospective studies

Table of random numbers

Eight studies detailed how patients were selected

(Table 4).8-10,15,19-21,27 Four described how data were
collected,18-21 two indicated that data collection was from
databases,18,19 and two collected data from medical
records.20,21 The description of the dose of PLTs adminis-
tered varied, i.e., dose was stated as mL/kg or by the PLT
content of the unit transfused or the number of units
transfused (Table 4).
Heal, 1993, 199411,12
First author, year

Outcomes
Carr, 199013
Lee, 198914

Randomized controlled trials

The sample sizes for the controlled trials ranged from 26 to
40 patients (Table 5). Neither survival nor bleeding events

2446 TRANSFUSION Volume 49, November 2009

 TABLE 4. The quality of prospective and retrospective studies
First author, year Sampling Data collection PLT dose Primary outcome
Prospective
Julmy, 20098 Consecutive patients NA Infants: 10-15 mL/kg PLT increment after 1 hr
<2 years-0.5 SDA
>2 years-full SDA
at least 2 ¥ 1011
Heim, 20089 Consecutive patients NA 3 ¥ 1011 The effects of patient and product factors on the PLT increment
Jimenez, 200310 Consecutive patients NA 3 ¥ 1011 PLT increment with the same apheresis donor*
Balduini, 200115 Consecutive patients NA 66 ¥ 109-70 ¥ 109/U Factors associated with PLT increments
Aster, 196516 NR NA NR The effects of different anticoagulants and ABO compatibility on PLT recovery
Retrospective
Blumberg, 200827 Consecutive patients Medical records NR Survival associated with PLT transfusion
Aboul Enein, 200717 NR NR 7 ¥ 1011 Impact of donor and machine parameters on PLT yield
Slichter, 200518 NR Secondary analysis of an RCT 3.7 ¥ 1011-4.5 ¥ 1011 Characteristics influencing posttransfusion PLT increment
Lapierre, 200519 Consecutive patients Database 0.6 ¥ 1011/5 kg Occurrence of HVOD
Klumpp, 199620 Consecutive patients Medical records 4.2 ¥ 1011/PRD Factors associated with PLT transfusion refractoriness
Heal, 199421 Consecutive patients Medical records 6 PRD or 1 SDA The effects of leukoreduced ABO-identical PLTs on morbidity and mortality
Shanwell, 199122 NR NR 4.6 ¥ 1011 The effect of transfusion of ABO-incompatible PLTs
Heal, 198723 Consecutive patients NR NR To evaluate PLT crossmatching and to determine the impact of HLA and
ABO matching
24
Duquesnoy, 1979 NR NR NR The role of ABO compatibility on PLT transfusion therapy
Tosato, 197825 NR NR 4 units The effect of HLA compatibility on PLT increment
Van Eys, 197826 NR NR 1 unit/10 kg (0.89 ¥ 1011/unit) “Consequences of free PLT use”
* Only 24 paired transfusion were included for estimation of percentage of PLT recovery.
HLA = human leukocyte antigen; HVOD = hepatic venoocclusive disease; NA = not applicable; NR = not reported; PRD = pooled random donor; RCT = randomized controlled trial.

TABLE 5. Outcomes of randomized controlled trials

First author, Sample size Survival PLT Mean PLT Time to determine
year Treatment (number of patients) (months) Morbidity refractoriness (%) increment (¥109/L) PLT count
Heal, 1993, ABO identical 19 25 Less transfusions in first 30 days 36 6.6 ⫾ 7.9 Mean, 9 hr
199411,12 vs. 21 13 and during first admission with 75 5.2 ⫾ 7.9
Nonidentical p = 0.02* ABO-identical PLTs (p < 0.05)† p < 0.03‡ p < 0.01§¶
Carr, 199013 ABO identical 13 NR No transfusion reactions with ABO 8 Not significantly different 1 or 20 hr
vs. 13 incompatible; two patients had 69
ABO incompatible bleeding requiring transfusion p = 0.001¶**
support
Lee, 198914 ABO identical 40 NR NR NR First transfusion pair: 17.9 vs. 10 min
vs. 16.0 (ABO identical vs.
ABO incompatible incompatible, p = ns)¶††

Volume 49, November 2009

* Survival for patients achieving a complete remission.
† The type of transfusion, that is, RBCs or PLTs, was not specified.
‡ PLT refractoriness = CCI less than 7.5 ¥ 109/L at 1 hour, 6.0 ¥ 109/L at 12 hours, or 4.5 ¥ 109/L at 24 hours for three consecutive transfusions. PLT refractoriness was measured after 25
PLT transfusions.
§ Mean CCI ⫾ standard deviation for the first 25 transfusions.
¶ The primary outcome of the study.
** PLT refractoriness = three consecutive transfusions resulting in a 1-hour CCI < 4500/mL in the absence of clinical factors to impair increment.
†† Mean CCI = the mean CCI for the second transfusion pair 14,900/mL versus 9500/mL (ABO identical vs. incompatible, p < 0.0007).
NR = not reported.
ABO-MATCHED PLATELET TRANSFUSION

TRANSFUSION 2447
SHEHATA ET AL.
nor transfusion reactions was a primary endpoint in any
study. A post hoc analysis of one study demonstrated that
in a subgroup of patients with acute leukemia who
achieved a complete remission and received ABO-
identical PLT transfusion, survival was prolonged by 12
months.12 One study reported that there were no transfu-
sion reactions after ABO-incompatible PLT transfusions
and two patients receiving ABO-incompatible PLT trans-
fusion experienced bleeding requiring transfusion sup-
port.13 In two trials, the frequency of PLT refractoriness in
patients with various hematologic malignancies was
reduced by 39 and 61% with ABO-identical PLT transfu-
sions,11,13 and a reduction in the number of transfusions
was also demonstrated with ABO-identical PLT transfu-
sion.11 ABO-identical PLT transfusions were also associ-
ated with an increase of 6.6 ¥ 109 to 14.9 ¥ 109/L in the CCI
compared to nonidentical PLTs.11,14 In one of these studies,
a significant PLT increment with ABO-identical PLT trans-
fusion was only found after the second PLT transfusion
and not the first transfusion.14 The second study reported
as a secondary outcome that the type of ABO matching
affected the PLT increment.11 ABO-identical PLT transfu-
sions were associated with higher CCIs than ABO-
compatible or ABO-incompatible transfusions (7500 vs.
4800 vs. 3000, respectively; p < 0.05).11 The last study did
not demonstrate a difference in PLT increment with ABO-
identical PLT transfusion.13
Prospective and retrospective studies
Prospective studies. A 45% difference in PLT incre-
ments with ABO-compatible versus ABO-incompatible
PLT transfusion was found in one report, but significance
was not described.16 Another study demonstrated a
significant difference in the PLT increment with ABO-
identical compared to ABO-compatible PLT transfusion.10
Jimenez and colleagues10 randomly assigned recipients to
receive PLTs from a common donor. There was 30% differ-
ence in PLT recovery between ABO-identical and ABO-
compatible PLT transfusion when the data were analyzed
according to whether the recipients received PLTs from a
common donor.10 One study reported a lower percentage
of PLT recovery with ABO-incompatible transfusions,8
and another study reported a lower CCI with ABO-
mismatched transfusions.9 The remaining study did not
find a difference in PLT increment with ABO-identical or
ABO-compatible PLT transfusion.15
Retrospective studies. A total of 1214 individuals
were included in the 11 retrospective studies (Table 6). In
one report of 47 patients, no difference in survival after
3 years was observed with leukoreduced ABO-identical
PLT transfusion compared to nonleukoreduced ABO-
mismatched transfusion, but the study was underpow-
ered to detect potentially meaningful differences.21 The
adverse effects or morbidities described included days
with hemorrhage, hepatic venoocclusive disease, transfu-
2448 TRANSFUSION Volume 49, November 2009
sion of RBCs and PLTs, and length of stay. In recipients of
autologous marrow transplants for lymphoma, there was
no difference in the number of days with hemorrhage (0.2
days with leukoreduced predominantly ABO identical PLT
transfusion and 0.3 days for nonleukoreduced predomi-
nantly ABO-unmatched PLT transfusions; p = not signifi-
cant). The same investigators also did not find a difference
in mortality (defined as mean survival months at last
follow-up/death) during induction therapy in 115 patients
with acute leukemia who received ABO-identical PLT
transfusion compared to ABO-unmatched transfusion,
but a difference in survival was reported to be improved
for patients receiving washed leukoreduced ABO-
identical PLT transfusion compared to ABO-unmatched
transfusion (p = 0.02).27 In pediatric patients undergoing
autologous hematopoietic stem cell transplantation,
ABO-identical PLT transfusion was associated with a 17%
reduction in the incidence of hepatic venoocclusive
disease compared to ABO-compatible transfusion
(p = 0.02).19 Of the seven studies that included the PLT
increment as an outcome,17,18,20,23-26 four reported a signifi-
cantly higher increment with ABO-identical/-compatible
PLT transfusions compared with non–ABO-identical
transfusions,18,20,23,24 two reported an increase with ABO-
compatible PLT transfusion compared to ABO-
incompatible transfusion but did not provide data for the
increment with ABO-nonidentical transfusion,17,18 one
reported an increase with ABO-compatible compared to
ABO-incompatible PLT transfusion that was not signifi-
cant,25 and one study did not demonstrate an increased
PLT increment with ABO-identical PLT transfusion
(Table 6).26 Only three studies compared outcomes with
ABO-identical versus ABO-compatible PLT transfusion;
19,22,23
two of the three demonstrated improved outcomes
with ABO-identical PLT transfusion.19,23
In 47 patients with lymphoma undergoing autolo-
gous BMT, leukoreduced ABO-identical PLT transfusion
was found to be associated with fewer PLT transfusions
(mean, 74 for leukoreduced predominantly ABO-identical
PLT transfusion versus 151 for nonleukoreduced predomi-
nantly ABO-unmatched PLT transfusions; p = 0.003) and
fewer RBC transfusions (mean, 9 vs. 16, respectively;
p = 0.02).21 In a second study of 81 allogeneic marrow
recipients, there was no significant difference between
ABO-identical versus ABO-compatible PLTs in mean
number of PLT transfusions (16.3 ⫾ 20.7 for ABO-identical
vs. 15.1 ⫾ 16.6 with ABO-compatible) and mean number
of RBC units transfused (5.3 ⫾ 5.5 for ABO-identical com-
pared to 4.6 ⫾ 3.7 ABO-compatible PLT transfusion).22 In
patients with acute leukemia, there was also no difference
in mean number of PLT transfusions (137 ⫾ 100 for ABO-
unmatched compared to 125 ⫾ 124 for ABO-identical)
and mean number of RBC units transfused (17 ⫾ 12 for
ABO-unmatched compared to 16 ⫾ 8 for ABO-identical).27
Hemolysis did not appear to occur with ABO-compatible
 ABO-MATCHED PLATELET TRANSFUSION

TABLE 6. Outcomes of prospective and retrospective studies

First author, PLT
year Treatment Sample size Mortality Morbidity refractoriness PLT increment
Prospective
Julmy, ABO identical vs. 282 NR No “detectable” hemolytic NR OR for PPR, <30% 4.0
20098 ABO compatible vs. 42 transfusion reactions (95% CI, 1.5 to 10.4) for ABO
ABO incompatible 76 nonidentical vs. ABO identical
transfusions
Heim, ABO identical vs. 5834 NR No reactions secondary to ABO NR HR 1 (CCI < 12.5)
20089* Minor mismatch vs. 1919 grouping 1.6
Major mismatch vs. 1715 1.5
Bidirectional 409 2.3
transfusions p < 0.01
Jimenez, ABO identical vs. 54 patients NR NR NR 70%
200310 ABO compatible 38%
p < 0.02†
Balduini, ABO identical vs. 87 patients NR NR NR 5720 ⫾ 8200
200115* ABO nonidentical 5870 ⫾ 8480
p = 0.8 after 16 hr‡
Aster, ABO compatible vs. 41 patients NR NR NR 63%
196516 A incompatible 19%
B incompatible 57%
AB incompatible 8%
(AB to O) p = NR after 1-4 hr
Retrospective
Blumberg, ABO identical vs. 46 30% No difference in length of stay, NR NR
200827* ABO unmatched vs. 18 33% RBCs/PLT transfused, fever
LR ABO identical vs. 29 34% or antibiotic use
washed LR ABO 25 16%
identical patients
Aboul Enein, ABO compatible vs. 15 NR NR NR 75% higher with compatible
200717* ABO incompatible 18 after 12-18 hr, p = NR
transfusions
Slichter, ABO compatible vs. 533 patients NR No difference in time to next No significant 4.6 ¥ 109/L higher with ABO
200518* ABO incompatible transfusion difference§ compatible, p < 0.001 after
1 hr
Lapierre, ABO identical vs. 186 patients NR HVOD 31% NR NR
200519* ABO compatible 48%
p = 0.02
(RR, 2.1; 95% CI, 1.3-3.3)
Klumpp, No major ABO 66 patients NR NR NR 6163 ⫾ 326
199620* mismatch vs. 3875 ⫾ 661
Major ABO mismatch¶ p = 0.006 after 1-24 hr**
Heal, Predominantly LR ABO 28 No Fewer units of PLTs and RBCs Not an Not an endpoint
199421 identical 19 difference transfused, shorter length of endpoint
vs. patients stay, fewer days to
Predominantly non-LR ANC ⱖ 500 ¥ 106/L, fewer
ABO nonidentical days with fever and antibiotics
with ABO identical; no
difference in the number of
days with hemorrhage
Shanwell, ABO identical vs. 47 NR No difference in number of NR NR
199122 ABO compatible 34 RBC/PLT transfusions; no
patients clinical evidence of hemolysis
Heal, ABO identical vs. 51 patients NR NR NR 10 ¥ 109/L
198723 ABO compatible vs. 8.2 ¥ 109/L
ABO incompatible 6.0 ¥ 109/L
p < 0.05)†† after 1 to 4 hr
Duquesnoy, ABO compatible vs. 91 patients NR NR NR 73 ⫾ 4
197924 ABO incompatible 55 ⫾ 5
p < 0.01
after 1 hr‡‡
Tosato, ABO compatible vs. 11 patients NR NR NR 5.9 ¥ 109 ⫾ 6.2 ¥ 109/L
197825* ABO incompatible 4.4 ¥ 109 ⫾ 6.1 ¥ 109/L
p = NS after 12-24 hr§§
Van Eys, ABO identical vs. 30 patients NR NR NR 32%
197826* ABO nonidentical 39%
p = NR¶¶
* The authors’ definitions of ABO compatibility were used.
† One-hour PLT recovery after receipt of PLTs from a common donor. This result is a secondary outcome. This difference is not observed at 4 or 24 hours.
‡ No difference in the CCI by univariate analysis.
§ PLT refractoriness was defined as two serial 1-hour PLT increments of less than 11 ¥ 109/L or CCI of 5000.
¶ Major ABO mismatch was not defined.
**CCI ⫾ standard deviation for major ABO mismatch between recipient and PLT product.
††Median CCI for ABO identical vs. plasma incompatible vs. PLT incompatible.
‡‡Mean percentage of PLT recovery after 1 hour ⫾ standard deviation for HLA-compatible PLTs.
§§Mean corrected PLT increment (postcount - precount/unit of PLTs ¥ BSA) ⫾ standard deviation.
¶¶32% with ABO-identical PLTs had a successful PLT transfusion compared to 39% with ABO nonidentical. A successful PLT transfusion was defined as the ces-
sation of bleeding or a PLT increment of at least 20 ¥ 109/L.
ANC = absolute neutrophil count; HR = hazard ratio; HVOD = hepatic venoocclusive disease; LR = leukoreduced; NR = not reported; NS = not significant;
PPR = percentage of PLT recovery; RR = relative risk.

Volume 49, November 2009 TRANSFUSION 2449

SHEHATA ET AL.
PLT transfusion.22 There was no difference found in PLT
refractoriness associated with ABO-identical versus ABO-
nonidentical PLT transfusion.18
DISCUSSION
In this first systematic review to assess whether ABO
matching of PLTs improves morbidity and mortality in
hematology/oncology patients, we found that ABO-
identical PLT transfusion was associated with a higher PLT
increment. However, there was inconclusive data avail-
able to determine whether ABO matching affects mortal-
ity (aside from the rare events of hemolytic transfusion
reactions), bleeding events, or transfusion reactions as
none of the studies used these measures as primary out-
comes and none was powered to detect a difference in
these outcomes.
When addressing the effect of ABO-identical PLT
transfusion, it is important to consider a hierarchy of
transfusion outcomes. Mortality and morbidity, that is,
hemorrhage and transfusion reactions, are the most
important clinical outcomes. All other outcomes are sec-
ondary outcomes, for example, PLT refractoriness, and
length of stay or resource utilization outcomes, that is,
utilization of RBCs and PLTs. The PLT increment can also
be considered a secondary outcome, although it is not a
clinical outcome, as a higher PLT recovery may be a sur-
rogate marker for the reduced risk of bleeding.
Survival was demonstrated to be improved in a post
hoc analysis of one randomized controlled trial of a sub-
group of individuals with acute leukemia that received
ABO-identical PLT transfusion, but this result was not
substantiated in two observational reports by the same
authors of individuals receiving autologous or peripheral
stem cell transplantation21 and in patients with acute
leukemia.27 The latter report, however, indicated that
survival was improved for patients receiving washed
leukoreduced ABO-identical PLTs compared to
unmatched PLTs. Two retrospective reports of ABO-
identical PLT transfusion in patients undergoing cardio-
vascular surgery28,29 and one retrospective report in
patients receiving ABO-incompatible plasma suggest that
there may be an increased risk of mortality with ABO-
nonidentical PLT or large-volume plasma transfusion
(relative risk, 1.15; 95% confidence interval [CI], 1.02-
1.29).30 Based on these data, it is difficult to conclude
what the effect of ABO matching is on survival in
hematology/oncology patients.
Of the two studies13,21 that reported bleeding events,
the definition of hemorrhage and bleeding was not clearly
defined. Carr and colleagues13 reported that there were no
transfusion reactions attributable to ABO-incompatible
PLT transfusions, and Shanwell and colleagues22 indicated
that there was no evidence of hemolysis with ABO-
compatible PLT transfusions, but the sample sizes of the
2450 TRANSFUSION Volume 49, November 2009
studies were small so they were likely not adequately
powered to detect a clinically significant difference in
transfusion reactions.
There were conflicting results for the effect of ABO-
identical transfusion on PLT and RBC transfusion and PLT
refractoriness. ABO-identical PLT transfusion was found
to be associated with a reduction on RBC and PLT trans-
fusion in two11,21 of four studies.22,27 The difference in
results is likely secondary to confounding variables,
because the studies were small. Two randomized con-
trolled trials found a reduction in PLT refractoriness
with ABO-identical PLT transfusion11,13 but a retrospective
report did not find a difference in the frequency of PLT
refractoriness with ABO-compatible PLT transfusion. The
conflicting results on the effect of PLT refractoriness may
have been due to a difference in definitions of PLT refrac-
toriness or a difference in the ABO-matched product used
for the analysis, that is, the two randomized controlled
trials11,13 compared ABO-identical PLT transfusion to
nonidentical transfusion11 and incompatible PLT transfu-
sion,13 whereas the retrospective analysis analyzed the
effect of ABO identical versus compatible transfusions.18
Thus, ABO-identical PLT transfusion appears to reduce
the frequency of PLT refractoriness compared to ABO-
nonidentical PLT transfusion, but it has yet to be deter-
mined whether ABO-identical PLT transfusion reduces
the frequency of PLT refractoriness compared to ABO-
compatible PLT transfusion.
There were two prospective8,10 and three retrospec-
tive cohort studies19,22,23 that compared ABO-identical
and ABO-compatible PLT transfusion. Two of the five
studies reported a higher increment in PLTs with ABO-
identical PLT transfusion.10,23 One study did not define
ABO compatibility clearly,9 and the remaining two
studies did not report on this outcome.19,22 There was an
increased frequency with hepatic venoocclusive disease
with ABO-compatible PLT transfusion compared to ABO-
identical PLT transfusion found in one study19 and the
significance of this outcome needs to be confirmed
because this result has not been reported by other
investigators.
It is important to consider why outcomes are not con-
sistent. Causality for mortality and morbidity is subject to
confounding variables in observational studies and there
are abundant confounding variables associated with the
outcomes of a PLT transfusion. The effect of PLT transfu-
sion reflects recipient factors (e.g., immunosuppressive
drugs, infections, sepsis) and donor factors such as the
variability of expression of AB antigens31-33 as well as PLT
factors such as the PLT count and quality of the PLT trans-
fusion product. There may also be a cumulative effect on
the PLT increment with ABO-identical PLT transfusion,
which may not be detected if the PLT increment is only
assessed after the first or second transfusion.34 Finally,
there is a lack of discrimination between different types of

ABO incompatibility in published reports (i.e., plasma or
PLT incompatibility).11
The PLT increment may be used as a surrogate
outcome for bleeding. However, this assumes that there is
a correlation between the PLT increment and the risk of
bleeding. Although it is intuitive that an increase in PLT
number may reduce bleeding events and potentially mor-
tality, the PLT increment required to reduce bleeding risk
has not been determined. Preliminary results from a large
randomized controlled trial comparing different prophy-
lactic PLT doses do not show any differences in bleeding
associated with increased PLT count increments.35
However, one small retrospective analysis showed that
PLT refractoriness, as defined by a 1-hour CCI below 7.5
and/or a 24-hour CCI below 4.5, was associated with
increased bleeding complications (odds ratio [OR], 3.4;
95% CI, 1.1-11) and decreased 100-day survival (98% for
individuals not experiencing PLT transfusion refractori-
ness compared to 83% with a low CCI after 24 hours,
p < 0.01).36 The level of thrombocytopenia, however, was
not associated with an increased bleeding risk.36 These
results need to be substantiated. Higher PLT count incre-
ments may also be used as a surrogate for reduced PLT
transfusion requirements. However, a reduction in PLT
requirements was only found in one21 of the two studies
reporting this outcome. Therefore, the greater PLT incre-
ments seen with ABO-compatible or -identical transfu-
sions may not result in meaningful differences in the
number of PLT transfusions or the number of PLT units
transfused. This may be due to the small differences in the
increments or due to the small sample sizes of the studies.
Since the clinical significance of an increment is not
known, mortality and serious bleeding events are the pre-
ferred evaluation outcomes.37
There are other surrogate measures that have been
used to assess ABO-identical PLT transfusion. The Hb
concentration has been used as a surrogate marker for
hemolytic transfusion reactions.6 In one small study of 16
patients with hematologic and oncologic malignancies
who received ABO-identical or -nonidentical PLT transfu-
sion, transfusion of ABO-identical PLT transfusion did not
result in a significant change in Hb concentration.6 The
significance of the use of the Hb concentration as a surro-
gate marker for hemolytic transfusion reactions remains
to be determined.
Although there have been a number of studies
addressing the effect of ABO PLT matching, the majority of
the studies have been observational and are susceptible to
important sources of bias. This systematic review, thus,
has several strengths including the use of a predefined
systematic search strategy, a duplicate review of all cita-
tions, and structured data abstraction. These approaches
limit bias on the part of the reviewers. In addition, by
reviewing all the studies, we were able to determine
whether there is a tendency to improved effects with ABO-
ABO-MATCHED PLATELET TRANSFUSION
identical transfusion in hematology/oncology patients.
However, the results of this review must be interpreted
in the context of its limitations. The studies that were
included were heterogeneous with respect to the patient
populations, the PLT products used, the definitions of
incompatibility, and the reported outcomes considered.
The sample sizes were small and there were no studies
that were powered to detect a difference in mortality or in
adverse events (i.e., bleeding or transfusion reactions).
Although one report did find a significant difference in
mortality with ABO-identical PLT transfusion,12 the
improved mortality was described only in a post hoc
analysis. In addition, a large proportion of studies were
uncontrolled, observational studies that are susceptible to
confounding in that not all known risk factors for transfu-
sion are included in the analysis. Furthermore, few studies
assessed the effect of ABO-identical PLT transfusion com-
pared to ABO-compatible transfusion,10,19,22,23 and three
demonstrated superior outcomes with ABO-identical
PLTs.10,19,23 Finally, the quality of the data in these studies
may be impacted by insufficient documentation, which is
a common limitation of retrospective studies.38
Although the studies included in this systematic
review had several limitations, we conclude that the pre-
ponderance of evidence suggests that ABO-identical PLT
transfusion is associated with a higher PLT increment.
However, the clinical significance of the greater PLT count
increments is not clear. Additionally, this systematic
review cannot make any conclusions regarding the effects
of ABO on mortality or morbidity. As there is an increased
risk of hemolytic transfusion reactions with ABO-
nonidentical PLT transfusion, the potential for increased
adverse events with transfusing ABO-nonidentical PLTs
should not be downplayed. Transfusion medicine services
should consider measures to increase ABO-identical PLT
transfusions and physicians should be aware of potential
adverse outcomes when transfusing ABO-nonidentical
PLTs. A large randomized controlled trial is needed to
determine the degree of benefit associated with ABO-
identical PLT transfusions compared to ABO-compatible
PLT transfusions, because supplying ABO-identical PLTs
to all patients has significant resource implications given
that there is currently a limited supply of these products
and demand may not match the need for these products.
A large randomized controlled trial powered to detect a
difference in morbidity (i.e., transfusion reactions and
bleeding events) and/or mortality, and that includes
standardized outcomes such as the degree of bleeding
and PLT refractoriness, would more clearly establish
the potential benefit of ABO-identical PLT transfusion.
In addition, future publications should clearly specify
whether PLT transfusions are ABO-compatible or ABO-
identical and should try to establish differences in
outcomes between ABO-identical and -compatible
transfusions.
Volume 49, November 2009 TRANSFUSION 2451
SHEHATA ET AL.
APPENDIX: SEARCH STRATEGY
1. ABO Blood-Group System/or “Blood Grouping and
Crossmatching”/or ABO matching.mp. (14232)
2. ABO identical.mp. (86)
3. ABO unmatched.mp. (24)
4. ABO blood group system.mp. or *ABO Blood-Group
System/ (11998)
5. ABO.mp. (14271)
6. Blood Group compatibility.mp. or Blood Group
Incompatibility/ (4701)
7. Blood group antigens.mp. or Blood Group Antigens/
(15276)
8. Platelet transfusion.mp. or Platelet Transfusion/
(4066)
9. Platelet refractoriness.mp. (104)
10. Platelet Count/ or Platelet Transfusion/ or platelet
increment.mp. (16178)
11. 1 or 2 or 3 or 4 or 5 or 6 or 7 (30780)
12. 8 or 9 or 10 (16820)
13. 11 and 12 (377)
14. Limit 13 to (humans and English language) (311)
15. Limit 13 to (humans and English language) (311)
16. From 15 keep 1-77 (77)
17. From 16 keep 1-77 (77)
ACKNOWLEDGMENT
We thank Dean Fergusson for his assistance with the manuscript.
CONFLICT OF INTEREST
None declared.
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