Transfusion and Apheresis Science xxx (xxxx) xxx–xxx

Contents lists available at ScienceDirect

Transfusion and Apheresis Science

journal homepage: www.elsevier.com/locate/transci

Reduction in adverse transfusion reactions with increased use of washed

platelet concentrates in Japan—A retrospective multicenter study
Emi Ikebea,1, Sahoko Matsuokaa,1, Asashi Tanakab, Yuji Yonemurac, Yasuhiko Fujiid,
Akimichi Ohsakae, Hitoshi Okazakif, Junichi Kitazawag,h, Shinichi Ohtanii, Takayuki Nakayamaj,
Shun-ya Momosek, Izumi Miwal, Rikizo Tairal, Kuro Toyotal, Shuichi Kinom, Hidefumi Katoj,
⁎
Isao Hamaguchia,
a
Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Tokyo, Japan
b
Department of Blood Transfusion, Tokyo Medical University Hachioji Medical Center, Tokyo, Japan
c
Department of Transfusion Medicine and Cell Therapy, Kumamoto University Hospital, Kumamoto, Japan
d
Department of Transfusion Medicine, Yamaguchi University Hospital, Yamaguchi, Japan
e
Department of Transfusion Medicine and Stem Cell Regulation, Juntendo University School of Medicine, Tokyo, Japan
f
Department of Transfusion Medicine, The University of Tokyo Hospital, Tokyo, Japan
g
Department of Transfusion Medicine and Transplantation Immunology, Fukushima Medical University, Fukushima, Japan
h
Division of Clinical Laboratory, Aomori Prefectural Central Hospital, Aomori, Japan
i
Department of Transfusion Medicine and Cell Transplantation, Kitasato University School of Medicine, Sagamihara, Japan
j
Department of Transfusion Medicine, Aichi Medical University, Aichi, Japan
k
Japanese Red Cross Kinki Block Blood Center, Osaka, Japan
l
Blood Service Headquarters, Japanese Red Cross Society, Tokyo, Japan
m
Japanese Red Cross Hokkaido Block Blood Center, Sapporo, Japan

A R T I C LE I N FO A B S T R A C T

Keywords: Plasma removal by washing platelet concentrates (PCs) is effective in preventing adverse reactions to PC
Washed platelet concentrate transfusions. The Japanese Red Cross Society (JRCS) started releasing washed PCs (WPCs) as a commercially
Replaced platelet concentrate approved blood product in September 2016. This retrospective multicenter study investigated the change in the
Adverse transfusion reaction number of transfused WPCs and the impact on the incidence of adverse reactions to PCs before and after the
Allergic transfusion reaction
release. The numbers and types of transfused PCs and the adverse reactions to the PCs for a year before the start
Hemovigilance
of the WPC release and for a year after the release were reported by 27 medical institutes in Japan. Transfusion
information for approximately 8% of the amount of PCs supplied in Japan was analyzed during the study period.
After the start of WPC release by the JRCS, the number of transfused WPCs doubled. The rate of adverse re-
actions to PCs decreased significantly (p = 0.0223), from 4.30% before the release to 4.05% after the release.
The rates of adverse reactions to unwashed and WPCs were 4.13% and 0.84%, respectively. Allergic adverse
reactions were significantly decreased after the release (3.60% before versus 3.37% after). No severe allergic
reactions to WPCs were reported. The release of WPCs by the JRCS significantly reduced transfusion-related
adverse reactions to PCs in Japan.

1. Introduction reactions to approximately 10% of transfused blood components in

Japan have been reported to the system. The incidence of adverse re-
Since 2007, we have been collecting information on the adverse actions associated with platelet concentrates (PCs) has been high—-
reactions to transfused blood components from Japanese medical in- between approximately 3% and 5%—in comparison to the rates asso-
stitutes using an online hemovigilance system, developed mainly by the ciated with red blood cell components or plasma components. The
Hemovigilance Committee of the Japan Society of Transfusion incidence of adverse reactions to PCs recorded in our system has also
Medicine and Cell Therapy (JSTMCT) [1]. Adverse transfusion been high in comparison to the rates reported in other countries. This

⁎
Corresponding author.
E-mail address: [email protected] (I. Hamaguchi).
1
These authors contributed equally to this work.

https://doi.org/10.1016/j.transci.2018.12.021
Received 22 October 2018; Received in revised form 27 December 2018; Accepted 31 December 2018
1473-0502/ © 2019 Elsevier Ltd. All rights reserved.

Please cite this article as: Ikebe, E., Transfusion and Apheresis Science, https://doi.org/10.1016/j.transci.2018.12.021
E. Ikebe et al. Transfusion and Apheresis Science xxx (xxxx) xxx–xxx

suggests that, in Japan, observation of transfused recipients is per- donor leukoreduced apheresis by the JRCS. Conventional unwashed
formed carefully, both during and after transfusions, according to the PCs were suspended in 200 mL of donor plasma and stored for up to 4
“Guidelines for the Implementation of Blood Transfusion Therapy” es- days before transfusion. WPCs were categorized as either “institute-
tablished by the Ministry of Health, Labour, and Welfare, so that even washed PCs (I-WPCs),” which were WPCs washed either in the medical
mild adverse reactions are not overlooked in the reports. institutes or in the JRCS with technical cooperation requested from
The adverse reactions caused by PCs are mostly allergic transfusion medical institutes, or “JRCS-released WPCs (R-WPCs),” which were
reactions (ATRs). Previous studies have suggested that inflammatory WPCs that the JRCS has been releasing as blood products since
cytokines and protein components in the plasma cause allergic reac- September 2016. The R-WPCs were washed with BRS-A that was ap-
tions [2–6]. Decreasing the volume of plasma by washing or by re- proximately a 1:20 mixture of an acid–citrate–dextrose formula A
placement with platelet additive solution (PAS) has been shown to be (ACD-A) solution and bicarbonate Ringer solution (BRS), re-suspended
effective in preventing adverse transfusion reactions. As the USA and in BRS-A [13]. R-WPC washing was performed by the cell processor
most of the countries in Europe use replaced PCs (RPCs), in which some ACP215 (Haemonetics Corporation, MA, USA) [16]. All WPCs were
portion of the plasma is replaced with PAS, there have been few mul- used within 48 h after washing.
ticenter studies on adverse transfusion reactions to washed PCs (WPCs)
[7–12]. In Japan, several medical institutes have been washing PCs 2.3. Statistical analysis
within the facility to prevent ATRs since the early 1990s, but it has not
been common. The Japanese Red Cross Society (JRCS) has developed Chi-square tests were performed to assess the significance of dif-
methods of washing PCs for the productization of WPCs [12,13]. In ferences in the rates of transfusion reactions. Statistical significance was
September 2016, at the request of many Japanese medical institutes considered to be indicated by p < 0.05.
and upon approval by the Ministry of Health, Labour and Welfare in
Japan, the JRCS began releasing WPCs commercially as a blood pro- 3. Results
duct. We performed a retrospective multicenter study to evaluate the
absolute number of WPC transfusions and related adverse reactions at 3.1. Increase in WPC transfusions associated with the WPC release
27 medical institutes that participate in our hemovigilance system
during the year before the start of the WPC release by the JRCS and the The absolute number of PCs used in transfusions in the medical
year after. institutes enrolled in the study during the study period (133,015 bags)
was 7.96% of the number of PCs that the JRCS supplied to Japanese
2. Materials and methods medical institutes (1,670,101 bags) during the same period (Fig. 1A).
The number of transfused WPCs during the year before the WPC release
2.1. Study design by the JRCS (825 bags) was 1.27% of the number of all transfused PCs
(64,726 bags), while the transfused WPCs in the year after the release
This was a retrospective observational analysis of data on PC (1670 bags, including 1,052 R-WPC bags) doubled to 2.45% of the
transfusions and associated adverse transfusion reactions over a period number of all transfused PCs (68,253 bags) (Fig. 1A). The percentage of
of two years, collected from 27 Japanese medical institutes enrolled in R-WPCs in all transfused PCs was small, 0.95%, in the months of Sep-
this study. The enrolled institutes have been reporting transfusion-re- tember and October 2016, just after the release but increased thereafter
lated adverse reactions regularly through our established hemovigi- to approximately 1.5% (Fig. 1B).
lance system for years. All the data were collected and analyzed by the
Department of Safety Research on Blood and Biological Products of the 3.2. Change in the incidence of adverse reactions to PCs associated with the
National Institute of Infectious Diseases. We collected data on the WPC release
numbers of transfused PCs and transfusion-related adverse reaction
reports from 26 medical institutes for the year preceding WPC release The incidence of adverse transfusion reactions to PCs (number of
(September 2015 to August 2016) and the year following (September adverse reactions/number of bags) was significantly decreased from
2016 to August 2017) and from one institute for only the year following 4.30% (2,783/64,762) in the year before the WPC release by the JRCS
(September 2016 to August 2017). We then compared the data for the to 4.05% (2,762/68,253) in the year after the release (p = 0.0223)
one-year periods before and after the WPC release. (Fig. 2A).
Transfusion-related adverse reactions were classified as non-hemo- Table 1 shows the types, clinical signs, and diagnoses of reported
lytic transfusion reactions, hemolytic transfusion reactions, and trans- adverse reactions to the unwashed PCs and WPCs over the two-year
fusion-transmitted infectious diseases. Non-hemolytic transfusion re- study period. During this period, there were no reports of hemolytic
actions were categorized as severe ATRs, transfusion-related acute lung reactions, transfusion-transmitted infections, TACO, TRALI, GVHD, or
injury (TRALI), transfusion-associated circulatory overload (TACO), PTP. The number of cases of serious ATRs decreased from thirteen
transfusion-associated graft-versus-host disease (TA-GVHD), post- before the release to eight after the release, which suggests the effect of
transfusion purpura (PTP), and others. Clinical signs and symptoms of the increased use of WPCs. All 21 serious ATRs that occurred over the
transfusion reactions were classified into 17 categories by the partici- study period were caused by unwashed PCs; none were reported with
pating medical institutes, as shown in Table 1. The definition of ATRs the use of WPCs. ATRs were significantly decreased after the WPC re-
used in this study was based on documents issued by the International lease (3.60% before → 3.37% after), as were rashes and hives (2.01%
Society of Blood Transfusion (ISBT) Working Party for Hemovigilance before → 1.83% after), itchiness (1.23% before → 1.21% after), and
[14]. The enrolled medical institutes monitored recipients during redness and facial flush (0.36% before → 0.33% after) (Fig. 2B). The
transfusion and reported the ATRs according to the standardized defi- incidence of febrile non-hemolytic reactions (FNHTRs) was essentially
nition as previously described [15]. The study was approved (approval unchanged by the release (0.24% before → 0.23% after).
number: 916) by the NIID Institutional Review Board, which is guided
by local policy, national law, and the World Medical Association De- 3.3. Comparison of adverse transfusion reactions to unwashed PCs and
claration of Helsinki. WPCs

2.2. Platelet concentrate characteristics We analyzed the incidence of adverse reactions to unwashed PCs
and WPCs during the year after the WPC release by the JRCS. Compared
All PCs used in transfusions in Japan are produced from single- to an incidence of 4.13% (2,748/66,583) for unwashed PCs, WPCs

2
E. Ikebe et al. Transfusion and Apheresis Science xxx (xxxx) xxx–xxx

Table 1
Number and incidence of adverse transfusion reactions to unwashed PCs and WPCs. Incidences (%) calculated by dividing the number of reactions by the number of
PC bags. *Before: period before the WPC release by JRCS, **After: period after the WPC release by JRCS.
Type of PC Unwashed PC WPC All PC

Before* After** Total Incidence Before After Total Incidence Before After Total Incidence

Number of unit 676929 703343 1380272 Total 8820 16654 25474 Total 685749 719997 1405746 Before After
Number of bag 63937 66583 130520 825 1670 2495 64762 68253 133015

(A) Non-hemolytic transfusion reactions 2781 2748 5529 4.24% 2 14 16 0.64% 2783 2762 5545 4.30% 4.05%
Severe allergic reaction 13 8 21 0.02% 0 0 0 0.00% 13 8 21 0.02% 0.01%
TRALI 0 0 0 0.00% 0 0 0 0.00% 0 0 0 0.00% 0.00%
TACO 0 0 0 0.00% 0 0 0 0.00% 0 0 0 0.00% 0.00%
TA-GVHD 0 0 0 0.00% 0 0 0 0.00% 0 0 0 0.00% 0.00%
PTP 1 0 1 0.00% 0 0 0 0.00% 1 0 1 0.00% 0.00%
Others[(Total of (1) to (17)] 2767 2740 5507 4.22% 2 14 16 0.64% 2769 2754 5523 4.28% 4.03%
(1) Fever 153 151 304 0.23% 1 3 4 0.16% 154 154 308 0.24% 0.23%
(2) Chills/Rigor 55 45 100 0.08% 0 1 1 0.04% 55 46 101 0.08% 0.07%
(3) Feverishness 47 58 105 0.08% 0 0 0 0.00% 47 58 105 0.07% 0.08%
(4) Pruritus 795 823 1618 1.24% 0 2 2 0.08% 795 825 1620 1.23% 1.21%
(5) Rash 235 223 458 0.35% 0 2 2 0.08% 235 225 460 0.36% 0.33%
(6) Urticaria 1299 1246 2545 1.95% 0 2 2 0.08% 1299 1248 2547 2.01% 1.83%
(7) Respiratory distress 54 55 109 0.08% 0 0 0 0.00% 54 55 109 0.08% 0.08%
(8) Nausea/Vomiting 28 24 52 0.04% 0 0 0 0.00% 28 24 52 0.04% 0.04%
(9) Chest, flank or back pain 11 6 17 0.01% 1 0 1 0.04% 12 6 18 0.02% 0.01%
(10) Headache 4 7 11 0.01% 0 0 0 0.00% 4 7 11 0.01% 0.01%
(11) Hypotensive reaction 35 31 66 0.05% 0 1 1 0.04% 35 32 67 0.05% 0.05%
(12) Hypertensive reaction 19 19 38 0.03% 0 1 1 0.04% 19 20 39 0.03% 0.03%
(13) Tachycardia 12 10 22 0.02% 0 1 1 0.04% 12 11 23 0.02% 0.02%
(14) Vein pain 1 2 3 0.00% 0 0 0 0.00% 1 2 3 0.00% 0.00%
(15) Disturbance of consciousness 2 3 5 0.00% 0 1 1 0.04% 2 4 6 0.00% 0.01%
(16) Hemoglobinuria 2 0 2 0.00% 0 0 0 0.00% 2 0 2 0.00% 0.00%
(17) Others 15 37 52 0.04% 0 0 0 0.00% 15 37 52 0.02% 0.05%
(B)Hemolytic transfusion reactions 0 0 0 0.00% 0 0 0 0.00% 0 0 0 0.00% 0.00%
Acute hemolytic reaction 0 0 0 0.00% 0 0 0 0.00% 0 0 0 0.00% 0.00%
Delayed hemolytic reaction 0 0 0 0.00% 0 0 0 0.00% 0 0 0 0.00% 0.00%
(C)Infectious disease 0 0 0 0.00% 0 0 0 0.00% 0 0 0 0.00% 0.00%
HBV 0 0 0 0.00% 0 0 0 0.00% 0 0 0 0.00% 0.00%
HCV 0 0 0 0.00% 0 0 0 0.00% 0 0 0 0.00% 0.00%
HIV 0 0 0 0.00% 0 0 0 0.00% 0 0 0 0.00% 0.00%
Bacteria 0 0 0 0.00% 0 0 0 0.00% 0 0 0 0.00% 0.00%
Others 0 0 0 0.00% 0 0 0 0.00% 0 0 0 0.00% 0.00%
Total (A)+(B)+(C) 2781 2748 5529 4.24% 2 14 16 0.64% 2783 2762 5545 4.30% 4.05%

Fig. 1. Changes in the number and portion of WPCs in all transfused PCs. (A) Number and portion of transfused PCs by type before and after the WPC release by the
JRCS. Before: period before the WPC release by JRCS, After: period after the WPC release by JRCS. (B) Number and portion of transfused PCs by type before and after
the WPC release by the JRCS, every two months.

3
E. Ikebe et al. Transfusion and Apheresis Science xxx (xxxx) xxx–xxx

Fig. 2. Incidence of adverse transfusion reactions to PCs associated with the WPC release. (A) Incidence of adverse transfusion reactions to PCs before and after the
WPC release.
Incidences (%) calculated by dividing the number of reactions by the number of PC bags. Before: period before the WPC release by JRCS, After: period after the WPC
release by JRCS. (B) Incidence of adverse transfusion reactions to PCs classified by clinical signs and symptoms before and after the WPC release. Incidences greater
than 0.2% are displayed in the figure.

Fig. 3. Incidence of adverse transfusion reactions to PCs before and after the WPC release. (A) Comparison of the incidence of adverse transfusion reactions to
unwashed PCs and WPCs after the WPC release. Incidences (%) calculated by dividing the number of reactions by the number of PC bags. (B) Comparison of the
incidence of adverse transfusion reactions to unwashed PCs, I-WPCs, and R-WPCs after the WPC release.

4
E. Ikebe et al. Transfusion and Apheresis Science xxx (xxxx) xxx–xxx

Fig. 4. Incidence of adverse transfusion reactions to unwashed PCs and WPCs by clinical signs and symptoms. Incidences (%) calculated by dividing the number of
reactions by the number of PC bags. Incidences greater than 0.1% are displayed in the figure.

showed a remarkably lower incidence of 0.84% (14/1,670) (Fig. 3A). reactions. The data in this study were strengthened by a well-estab-
The incidence of adverse reactions to R-WPCs was an extremely low lished and reliable reporting system and used to analyze adverse re-
0.48% (5/1,052) (Fig. 3B). The incidence of ATRs was significantly actions in a total of approximately 130,000 transfused PCs, including
reduced by washing (unwashed PCs, 3.44%; WPCs, 0.36%), as were the 2500 WPCs.
incidences of rashes and hives (unwashed PCs, 1.87%; WPCs, 0.12%), We found that the number of transfused WPCs increased two-fold
itchiness (unwashed PCs, 1.24%; WPCs, 0.12%), and redness and facial after the WPC release by the JRCS. This indicates that as a result of the
flush (unwashed PCs, 0.33%; WPCs, 0.12%) (Fig. 4). The incidence of WPC release, WPC transfusions increased even in medical institutes
ATRs associated with R-WPC was only 0.19% (2/1,052) in this study where preparation of WPCs was difficult in terms of the institutes’ own
(data not shown). No significant difference was observed between un- equipment and/or techniques used in Japan. The release of WPCs of a
washed PCs and WPCs in the incidence of FNHTRs (unwashed PCs, consistently high quality by the JRCS was innovative and valuable to
0.23%; WPCs, 0.18%). Japanese clinical medicine. The decrease in the occurrence of ATRs in
all PC transfusions after the WPC release could be strongly associated
with the increase in WPC transfusions. However, it is necessary to
4. Discussion continue to observe how the increase in WPC transfusions influences
the reduction in adverse reactions in PC transfusions in Japan, not just
In this study, we observed an increase in WPC transfusions fol- for one year after the release, but over a longer period of time.
lowing the nationwide WPC release and a reduction in adverse trans- In this study, ATRs associated with WPCs were observed to have
fusion reactions reported by 27 Japanese medical institutes for trans- dramatically decreased, which indicates that washing PC is effective in
fusions corresponding to approximately 8% of the number of PCs issued preventing ATRs, as has been previously reported [7–12]. It has also
in Japan during the study period. To the best of our knowledge, this been reported that the incidence of ATRs associated with RPCs is sig-
study is the largest study performed to date on the occurrence of ad- nificantly lower than that with unwashed PCs, but that it is still greater
verse reactions related to WPC transfusions (2482 WPC bags). There than 0.5% [10,11]. In the present study, the incidence of ATRs with
have been few multicenter studies on WPC transfusion-related adverse

5
E. Ikebe et al. Transfusion and Apheresis Science xxx (xxxx) xxx–xxx

WPCs was 0.36%, which indicates a greater effect in reducing ATRs blood donors and recipients and storage times from donation to trans-
than with RPCs, probably because of less remaining blood plasma in fusion, more detailed studies of the indications for and effect of WPCs in
WPCs than in RPCs. Notably, the incidence of ATR associated with preventing adverse reactions can be performed. As the use of either
WPCs was lower in this study than in other recent studies [7–9], WPC or unwashed PC for each patient is determined by each medical
probably because of few ATR cases being caused by R-WPC transfu- institute, uncertainty related to patient characteristics and institute
sions. Furthermore, in the present study, there were no cases of serious compliance with the JSTMCT guidance may be confounders in this
ATRs reported in association with WPC transfusions, which suggests the study. However, we speculate that it would be difficult to use WPC
possibility that serious ATRs can be prevented using WPCs. It is im- outside of the indications based on the current Japanese medical in-
portant to continue to collect adverse reaction reports to analyze to surance system. Therefore, our study demonstrated the increase in the
what extent serious ATRs could be prevented by washing PCs. As R- use of WPC and the decrease in ATRs after the release of WPC by the
WPC can only be stored up to 48 h after washing, the reduction in not JRCS.
only plasma but also storage time from blood collection to transfusion In conclusion, this retrospective multicenter study revealed that
might influence the decrease in ATRs. However, the influence would increased clinical use of WPCs associated with the WPC release appears
likely not be significant because PCs can only be transfused within 96 h to have reduced transfusion-related allergic adverse reactions to PCs
after blood collection in Japan. significantly. Novel R-WPCs produced by the JRCS are highly effective
There was no significant difference observed in this study in the in preventing adverse transfusion reactions.
incidence of FNHTRs associated with the use of unwashed PCs and
WPCs in transfusions, both of which were leukoreduced. Previous stu- Declaration of interest
dies demonstrated that washing PC mitigate febrile reactions [17,18].
Meanwhile, several studies have shown no differences between RPC None.
and conventional plasma PC transfusions in the frequency of FNHTRs
[10,19] or a higher frequency after transfusion of RPC than after Funding
transfusion of plasma PC [20]. As previous reports have suggested that
activated platelet (PLT)-derived soluble CD40 L could cause FNHTRs This work was supported in part by a grant from the Ministry of
[21,22], washing PC might not be effective in suppressing PLT activa- Health, Labour and Welfare of Japan [H28-iyaku-shitei-004] and by the
tion and subsequent soluble CD40 L production during preparation and Japan Society of Transfusion Medicine and Cell Therapy.
storage, in spite of the reduction in the volume of plasma containing
various potential pyrogenic substances. Further examination of the re- Acknowledgements
lationship between the storage period before transfusion after PC
washing and the incidence of FNHTRs is required. The authors thank all investigators who contributed valuable data in
The incidence of adverse reactions associated with R-WPCs was this retrospective study.
extremely low (0.48%) in this study, which indicates that R-WPCs yield
excellent results in reducing adverse reactions. It has been reported that Appendix A
the quality of PLTs washed with BRS-A is sufficiently maintained in vitro
[13,23]. A recent study also demonstrated that WPC containing BRS-A The authors are deeply grateful for the efforts of all participants who
is effective in reducing adverse transfusion reactions in children provided data for this study. The following Japanese medical institu-
without loss of transfusion efficacy [12]. However, it is essential to tions participated in this study: Aichi Medical University Hospital,
evaluate transfusion efficacy further by taking into consideration data Aomori Prefectural Central Hospital, Chiba University Hospital, Dokkyo
on the post-transfusion corrected count increment (CCI) and intervals of Medical University Hospital, Fukuoka University Hospital, Fukushima
transfusion to confirm the effectiveness and safety of R-WPC. Medical University Hospital, Hokkaido University Hospital, Jichi
Several European countries use only RPCs for transfusions, whereas Medical University Hospital, Juntendo University Hospital, Kindai
in Japan, the JSTMCT has indicated the following uses for W/RPCs in University Hospital, Kitasato University Hospital, Kumamoto University
its “Indication guidance for washed and replaced PLTs and their pre- Hospital, Kyushu University Hospital, Minamitama Hospital, Nagasaki
paration” [24]: (1) cases in which side effects that cannot be prevented University Hospital, Nagoya University Hospital, Osaka Medical College
with preadministration of various drugs are observed two or more times Hospital, St. Marianna University School of Medicine Yokohama City
or cases in which serious side effects such as anaphylactic shock are Seibu Hospital, The University of Tokyo Hospital, Toho University
observed once, and (2) cases in which only ABO-mismatched PC-HLA is Omori Medical Center, Tokai University Hospital, Tokyo Medical
available. W/RPCs apparently decrease allergic adverse reactions, but University Hachioji Medical Center, Toyama University Hospital,
the indication for W/RPCs for these uses should be considered along University of Fukui Hospital, University of Miyazaki Hospital,
with several other points, such as the influence on PLT count and University of Yamanashi Hospital, and Wakayama Medical University
function and the time, cost, and technology needed for preparation. Hospital.
Previous studies suggested that reducing the plasma concentration by
washing PCs might promote bacterial growth in WPCs [25–27]. It is References
also necessary to examine whether FNHTRs might be increased with W/
RPCs, in comparison to plasma PCs, by collecting more transfusion [1] Odaka C, Kato H, Otsubo H, Takamoto S, Okada Y, Taneichi M, et al. Online re-
data. Based on the results of the present study, which demonstrate the porting system for transfusion-related adverse events to enhance recipient haemo-
vigilance in Japan: a pilot study. Transfus Apher Sci 2013;48:95–102.
lower incidence of ATRs with WPCs compared to previous WPC retro- [2] Heddle NM, Klama L, Singer J, Richards C, Fedak P, Walker I, et al. The role of the
spective studies, WPC usage based on the JSTMCT guidance in Japan plasma from platelet concentrates in transfusion reactions. N Engl J Med
seems quite reasonable. As evidence-based effective usage of R-WPCs is 1994;331:625–8.
[3] Shimada E, Tadokoro K, Watanabe Y, Ikeda K, Niihara H, Maeda I, et al.
required in Japan, it is important to review the indications for W/RPC Anaphylactic transfusion reactions in haptoglobin-deficient patients with IgE and
uses prescribed in the JSTMCT guidance continuously through hemo- IgG haptoglobin antibodies. Transfusion 2002;42:766–73.
vigilance activities. Previous reports have suggested that im- [4] Savage WJ, Savage JH, Tobian AA, Thoburn C, Hamilton RG, Schroeder JT, et al.
Allergic agonists in apheresis platelet products are associated with allergic trans-
munological transfusion complications are related to both donor and
fusion reactions. Transfusion 2012;52:575–81.
recipient characteristics [15,28,29]. Prolonged storage times increase [5] Savage WJ, Savage JH, Tobian AA, Thoburn C, Hamilton RG, Schroeder JT, et al.
adverse reaction frequencies [30,31]. By supplementing existing he- Scratching the surface of allergic transfusion reactions. Transfusion
2013;53:1361–71.
movigilance activities with information about the ages and genders of

6
E. Ikebe et al. Transfusion and Apheresis Science xxx (xxxx) xxx–xxx

[6] Hirayama F. Current understanding of allergic transfusion reactions: incidence, 2010;50:2738–44.

pathogenesis, laboratory tests, prevention and treatment. Br J Haematol [19] de Wildt-Eggen J, Nauta S, Jg Schrijver, van Marwijk Kooy M, Bins M, van Prooijen
2013;160:434–44. HC, et al. Reactions and platelet increments after transfusion of platelet con-
[7] Azuma H, Hirayama J, Akino M, Miura R, Kiyama Y, Imai K, et al. Reduction in centrates in plasma or an additive solution: a prospective, randomized study.
adverse reactions to platelets by the removal of plasma supernatant and resuspen- Transfusion 2000;40:398–403.
sion in a new additive solution (M-sol). Transfusion 2009;49:214–8. [20] van Hout FMA, van der Meer PF, Wiersum-Osselton JC, Middelburg RA, Schipperus
[8] Tobian AA, Savage WJ, Tisch DJ, Thoman S, King KE, Ness PM. Prevention of al- MR, van der Bom JG, et al. Transfusion reactions after transfusion of platelets stored
lergic transfusion reactions to platelets and red blood cells through plasma reduc- in PAS-B, PAS-C, or plasma: a nationwide comparison. Transfusion
tion. Transfusion 2011;51:1676–83. 2018;58:1021–7.
[9] Yanagisawa R, Shimodaira S, Kojima S, Nakasone N, Ishikawa S, Momose K, et al. [21] Skripchenko A, Kurtz J, Moroff G, Wagner SJ. Platelet products prepared by dif-
Replaced platelet concentrates containing a new additive solution, M-sol: safety and ferent methods of sedimentation undergo platelet activation differently during
efficacy for pediatric patients. Transfusion 2013;53:2053–60. storage. Transfusion 2008;48:1469–77.
[10] Tobian AA, Fuller AK, Uglik K, Tisch DJ, Borge PD, Benjamin RJ, et al. The impact [22] Hamzeh-Cognasse H, Damien P, Nguyen KA, Arthaud CA, Eyraud MA, Chavarin P,
of platelet additive solution apheresis platelets on allergic transfusion reactions and et al. Immune-reactive soluble OX40 ligand, soluble CD40 ligand, and interleukin-
corrected count increment (CME). Transfusion 2014;54:1523–9. 27 are simultaneously oversecreted in platelet components associated with acute
[11] Cohn CS, Stubbs J, Schwartz J, Francis R, Goss C, Cushing M, et al. A comparison of transfusion reactions. Transfusion 2014;54:613–25.
adverse reaction rates for PAS C versus plasma platelet units. Transfusion [23] Iwama A, Hirayama J, Nogawa M, Shiba M, Satake M, Takamoto S, et al.
2014;54:1927–34. Comparison between in vitro properties of washed platelet concentrates suspended
[12] Kobayashi J, Yanagisawa R, Ono T, Tatsuzawa Y, Tokutake Y, Kubota N, et al. in M-sol and those in BRS-A, both of which were prepared with an automated cell
Administration of platelet concentrates suspended in bicarbonated Ringer’s solution processor. Transfus Apher Sci 2017;56:241–4.
in children who had platelet transfusion reactions. Vox Sang 2018;113:128–35. [24] Indication guidance for washed and replaced platelets and their preparation.
[13] Oikawa S, Sasaki D, Kikuchi M, Sawamura Y, Itoh T. Comparative in vitro eva- Version V. (http://yuketsu.jstmct.or.jp/medical/guidelines/).
luation of apheresis platelets stored with 100% plasma versus bicarbonated Ringer’s [25] Greco CA, Zhang JG, Kalab M, Yi QL, Ramirez-Arcos SM, Gyongyossy-Issa MI. Effect
solution with less than 5% plasma. Transfusion 2013;53:655–60. of platelet additive solution on bacterial dynamics and their influence on platelet
[14] ISBT Working Party on Haemovigilance. Proposed standard definitions for sur- quality in stored platelet concentrates. Transfusion 2010;50:2344–52.
veillance of non-infectious adverse transfusion reactions [cited 2013 Nov 9]. [26] Dumont LJ, Wood TA, Housman M, Herschel L, Brantigan B, Heber C, et al.
Available from:. Amsterdam: International Haemovigi-lance Network, International Bacterial growth kinetics in ACD-A apheresis platelets: comparison of plasma and
Society of Blood Transfusion; 2011http://www.isbtweb.org/fileadmin/user_ PAS III storage. Transfusion 2011;51:1079–85.
upload/files-2015/haemovigilance/definitions/Proposed%20definitions [27] Hirayama J, Azuma H, Fujihara M, Akino M, Homma C, Kato T, et al. Comparison
%202011%20surveillance%20non%20infectious%20adverse%20reactions between bacterial growth in platelets (PLTs) washed with M-sol and that in PLT-rich
%20haemovigilance%20incl%20TRALI%20correction%202013.pdf. plasma. Transfusion 2011;51:1592–4.
[15] Kato H, Nakayama T, Uruma M, Okuyama Y, Handa M, Tomiyama Y, et al. [28] Brand A. Immunological aspects of blood transfusions. Transpl Immunol
Repeated exposure rather than the total volume of transfused components may 2002;10:183–90.
influence the incidence of allergic transfusion reactions. Transfusion [29] Caram-Deelder C, Kreuger AL, Evers D, de Vooght KMK, van de Kerkhof D, Visser O,
2015;55:2576–81. et al. Association of blood transfusion from female donors with and without a
[16] Oikawa S, Sasaki D, Kikuchi M, Sawamura Y, Itoh T. Feasibility of a closed-system history of pregnancy with mortality among male and female transfusion recipients.
cell processor (ACP215) for automated preparation of washed platelet concentrates. JAMA 2017;318:1471–8.
Vox Sang 2012;102:110–5. [30] Kreuger AL, Caram-Deelder C, Jacobse J, Kerkhoffs JL, van der Bom JG, Middelburg
[17] Vo TD, Cowles J, Heal JM, Blumberg N. Platelet washing to prevent recurrent RA. Effect of storage time of platelet products on clinical outcomes after transfusion:
febrile Reactions to leucocyte-reduced transfusions. Transfus Med 2001;11:45–7. a systematic review and meta-analyses. Vox Sang 2017;112:291–300.
[18] Blumberg N, Heal JM, Gettings KF, Phipps RP, Masel D, Refaai MA, et al. An as- [31] Losos M, Biller E, Li J, Blower L, Hamad D, Patel G, et al. Prolonged platelet storage
sociation between decreased cardiopulmonary complications (transfusion-related associated with increased frequency of transfusion-related adverse events. Vox Sang
acute lung injury and transfusion-associated circulatory overload) and im- 2018;113:170–6.
plementation of universal leukoreduction of blood transfusions. Transfusion