Cryopreserved platelets in bleeding management in remote hospitals: A clinical feasibility study in Sweden

Abstract

Background
Balanced transfusions, including platelets, are critical for bleeding patients to maintain hemostasis. Many rural hospitals have no or limited platelet inventory, with several hours of transport time from larger hospitals. This study aimed to evaluate the feasibility of using cryopreserved platelets that can be stored for years, in remote hospitals with no or limited platelet inventory.

Material and methods
Three remote hospitals participated in a prospective study including adult bleeding patients where platelet transfusions were indicated. Cryopreserved platelets were prepared in a university hospital, concentrated in 10 ml, transported on dry ice, and stored at −80°C at the receiving hospital. At request, the concentrated platelet units were thawed and diluted in fresh frozen plasma. The indications, blood transfusion needs, and laboratory parameters pre- and post-transfusion, as well as logistics, such as time from request to transfusion and work efforts in preparing cryopreserved platelets, were evaluated.

Results
Twenty-three bleeding patients were included. Nine patients (39%) were treated for gastrointestinal bleeding, five (22%) for perioperative bleeding, and four (17%) for trauma bleeding. The transfusion needs were 4.9 ± 3.3 red blood cell units, 3.2 ± 2.3 plasma units, and 1.9 ± 2.2 platelet units, whereof cryopreserved were 1.5 ± 1.1 (mean ± SD). One patient had a mild allergic reaction. We could not show the difference in laboratory results between pre- and post-transfusion of the cryopreserved units in the bleeding patients. The mean time from the order of cryopreserved platelets to transfusion was 64 min, with a range from 25 to 180 min.

Conclusion
Cryopreserved platelets in remote hospitals are logistically feasible in the treatment of bleeding. The ability to have platelets in stock reduces the time to platelet transfusion in bleeding patients where the alternative often is many hours delay. Clinical effectiveness and safety previously shown in other studies are supported in this small feasibility study.

Full text

TYPE Original Research
PUBLISHED 20 January 2023
DOI 10.3389/fpubh.2022.1073318
OPEN ACCESS
EDITED BY
Marta Zarà,
Monzino Cardiology Center (IRCCS), Italy
REVIEWED BY
Juergen Grafeneder,
Medical University of Vienna, Austria
Emanuela Parotto,
Independent Researcher, Padua, Italy
*CORRESPONDENCE
Agneta Wikman
agneta.wikman@ki.se
SPECIALTY SECTION
This article was submitted to
Disaster and Emergency Medicine,
a section of the journal
Frontiers in Public Health
RECEIVED 18 October 2022
ACCEPTED 27 December 2022
PUBLISHED 20 January 2023
CITATION
Wikman A, Diedrich B, Björling K, Forsberg P-O,
Harstad A-M, Henningsson R, Höglund P,
Sköld H, Östman L and Sandgren P (2023)
Cryopreserved platelets in bleeding
management in remote hospitals: A clinical
feasibility study in Sweden.
Front. Public Health 10:1073318.
doi: 10.3389/fpubh.2022.1073318
COPYRIGHT
©2023 Wikman, Diedrich, Björling, Forsberg,
Harstad, Henningsson, Höglund, Sköld, Östman
and Sandgren. This is an open-access article
distributed under the terms of the Creative
Commons Attribution License (CC BY). The use,
distribution or reproduction in other forums is
permitted, provided the original author(s) and
the copyright owner(s) are credited and that
the original publication in this journal is cited, in
accordance with accepted academic practice.
No use, distribution or reproduction is
permitted which does not comply with these
terms.
Cryopreserved platelets in bleeding
management in remote hospitals: A
clinical feasibility study in Sweden
Agneta Wikman1,2*, Beatrice Diedrich1,2, Karl Björling3,
Per-Olof Forsberg4, Anna-Maria Harstad5, Ragnar Henningsson5,
Petter Höglund1,6, Hans Sköld7, Lars Östman3and Per Sandgren1,2
1Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden,
2Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm,
Sweden, 3Department of Anaesthesiology and Intensive Care, Visby Hospital, Visby, Sweden, 4Department
Laboratory Medicine, Central Hospital of Karlstad, Karlstad, Sweden, 5Department of Anaesthesiology and
Intensive Care, Central Hospital of Karlstad, Karlstad, Sweden, 6Center for Hematology and Regenerative
Medicine, Department of Medicine, Huddinge Karolinska Institutet, Stockholm, Sweden, 7Department of
Anaesthesiology and Intensive Care, Torsby Hospital, Torsby, Sweden
Background: Balanced transfusions, including platelets, are critical for bleeding
patients to maintain hemostasis. Many rural hospitals have no or limited platelet
inventory, with several hours of transport time from larger hospitals. This study aimed
to evaluate the feasibility of using cryopreserved platelets that can be stored for years,
in remote hospitals with no or limited platelet inventory.
Material and methods: Three remote hospitals participated in a prospective
study including adult bleeding patients where platelet transfusions were indicated.
Cryopreserved platelets were prepared in a university hospital, concentrated in 10 ml,
transported on dry ice, and stored at −80◦C at the receiving hospital. At request,
the concentrated platelet units were thawed and diluted in fresh frozen plasma.
The indications, blood transfusion needs, and laboratory parameters pre- and post-
transfusion, as well as logistics, such as time from request to transfusion and work
eorts in preparing cryopreserved platelets, were evaluated.
Results: Twenty-three bleeding patients were included. Nine patients (39%) were
treated for gastrointestinal bleeding, five (22%) for perioperative bleeding, and four
(17%) for trauma bleeding. The transfusion needs were 4.9 ±3.3 red blood cell
units, 3.2 ±2.3 plasma units, and 1.9 ±2.2 platelet units, whereof cryopreserved
were 1.5 ±1.1 (mean ±SD). One patient had a mild allergic reaction. We could
not show the dierence in laboratory results between pre- and post-transfusion of
the cryopreserved units in the bleeding patients. The mean time from the order of
cryopreserved platelets to transfusion was 64 min, with a range from 25 to 180 min.
Conclusion: Cryopreserved platelets in remote hospitals are logistically feasible in the
treatment of bleeding. The ability to have platelets in stock reduces the time to platelet
transfusion in bleeding patients where the alternative often is many hours delay.
Clinical eectiveness and safety previously shown in other studies are supported in
this small feasibility study.
KEYWORDS
BLEE-bleeding, platelets (PLT), blood transfusion, urban or rural, cryopreservation,
preparedness activities
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Wikman et al. 10.3389/fpubh.2022.1073318
Introduction
The availability of blood products in small remote hospitals is
often limited and without reserve capacity. The blood inventory is
planned according to normal usage, aiming for low wastage. With
long transport time to larger hospitals, these hospitals occasionally
treat patients with large bleeding, due to trauma, obstetric bleeding,
gastrointestinal bleeding, and unexpected bleeding in surgical
procedures. If massive bleeding occurs, the blood stock can quickly be
emptied. The most critical blood product in rural settings is platelets.
Platelets have a short shelf time of 5–7 days and are a product
with high cost. In massive bleeding cases a small stock of platelets,
often 1-2 units is insufficient, but results in high wastage most of
the time (1). As a result, many smaller hospitals have no platelets
stored locally, leading to several hours of delay before treatment. In
treatment guidelines for bleeding, the early use of blood products is
recommended and has improved survival (2,3). Platelets are crucial
for hemostasis in bleeding patients (4) resulting in reduced use of
red blood cells and plasma products, which is important in hospitals
with limited blood inventory (5). In addition, many patients are on
life-long treatment with anti-coagulant and platelet inhibitory drugs,
with an increased risk of bleeding, as a consequence. Cold-stored
platelets with up to 2 weeks of storage time have been evaluated in
the treatment of bleeding (6). This may facilitate the logistics but
probably not enough to ensure a supply in occasional bleeding.
Cryopreserved platelets extend platelet shelf life and the
upper limit for storage has currently been set to 1 year in the
European Guide to the preparation, use, and quality assurance
of blood components (EDQM) (7). However, studies indicate an
extended shelf life of up to 12 years (8), which will make it
possible to have a platelet stock in remote hospitals. Cryopreserved
platelets have been used on special indications since the 1970s,
and the early use was most often in refractory hematologic
patients (9). The freezing protocols have been evaluated and
improved, and the standard is now 5–6% dimethyl sulfoxide
(DMSO) and dilution in plasma. The platelet recovery after thawing
varies in different reports but is most often 50–70% (10,11).
Cryopreserved platelets have been extensively evaluated in vitro
after thawing and are judged functional and hemostatically effective
(12). In contrast, the recovery rate is 60–70% on average, and
a comprehensive in vitro characterization of the cryopreserved
platelets before clinical studies has been presented in recent
publications. We have analyzed and evaluated the ultrastructural
and functional effects (13), hemostatic responsiveness and the
release of biological response modifiers (14), cryopreservation of
platelets using different freezing rate protocols (14), and the
potential effects of cryopreservation on the interaction with different
plasma derivates (15). Cryopreserved platelets are preactivated and
adhere to activated endothelium and are not recommended as
prophylactic transfusions.
Frozen platelets have been used in military trauma casualties,
with good clinical effects and no reported adverse reactions (16,
17). The first clinical randomized trial was published in 1999, 73
cardiac surgery patients received cryopreserved or standard fresh
platelets (18). The patients treated with cryopreserved platelets
needed significantly fewer blood transfusions and no adverse effects
were seen. Cryopreserved vs. Liquid Platelets (CLIPs), a pilot study
in perioperative bleeding in Australia, and a pilot study from New
Zealand were recently published (19,20). Both studies support
the safety of cryopreserved platelets. Cryopreserved platelets are
approved and described in the EDQM (7).
In Scandinavia, as well as in Australia and New Zealand, and
reported from the USA and Canada (21), there are many rural
hospitals with limited blood stock and no platelets available.
The primary aim of this prospective observational study was to
evaluate the challenges with logistics, in remote hospitals with no
or limited platelet inventory, with the secondary aim of assessing
clinical demand, indications, and the effect of using cryopreserved
platelets in bleeding. This feasibility study lays the foundation for
further investigations to more comprehensively assess the hemostatic
effectiveness of cryopreserved platelets in remote locations.
Materials and methods
Study design
From August 2019 to December 2021, three hospitals participated
in a prospective study including adult bleeding patients where platelet
transfusions were indicated. When a platelet unit was ordered, a
frozen platelet could be chosen. Two of the hospitals normally also
had fresh platelets in stock, but one of the hospitals had no other
platelets. If there were fresh platelets available, we left it up to the
clinician to decide. We did not know the challenges and time it would
be to prepare platelets in a small laboratory, and did not want delay
transfusion in a bleeding patient.
Study hospitals
Two hospitals with remote locations participated. One larger
regional hospital participated in the last period, out of interest
to evaluate frozen platelets as a backup stock.Visby Hospital is
a general hospital located on an island with limited transport
opportunities in emergency situations. The hospital has ∼140 beds,
offering healthcare to more than 60,000 inhabitants, which would
double during the summertime. The hospital has elective and trauma
surgery, an emergency department, an intensive care unit (ICU),
and a delivery ward with 500–600 deliveries annually. The normal
blood inventory is ∼140 red blood cell (RBC) units, 100 fresh frozen
plasma (FFP) units, and 2–4 units of platelets. In 2019, more than
2000 RBC units, close to 200 plasma units, and 200 platelet units
were transfused.
Torsby Hospital is located in a small city close to the border with
Norway, with a drive time of 1.5–2 h to a larger hospital. The hospital
has 90 beds in three wards, an ICU with four beds, and an intensive
medical department with three beds. The hospital serves a population
of 10,000 with an emergency department, general and orthopedic
surgery, internal medicine, and gynecology, but not deliveries. The
inventory is 66 RBC units, 18 plasma units (3 liquid), and no platelets.
In 2019, the use of blood included ∼800 RBC units, 50 plasma units,
and 12 units of platelets.
Karlstad Hospital is a 450-bed regional hospital offering
specialized care in an area with long distances in the western part of
the country. Annually 20,000 surgical procedures and 2,700 deliveries
are done. Helicopter and land-based ambulances have many acute
means of transport.
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The helicopter carries two units of whole blood. The normal
blood inventory is 270 RBC units, 100 plasma units (6 liquid), and
10 platelet units. In 2019, 8500 RBC units, 650 plasma units, 1200
platelet units, and 18 whole blood units were transfused.
Inclusion of patients and evaluation of
frozen platelets
During 2019–2021, consecutive bleeding patients in the two small
rural hospitals were included. In 2021, a third regional hospital was
added and included three additional patients. Frozen platelets were
used in clinical indications in bleeding adult patients. They were
not used for prophylactic transfusions. Inclusion of patients, clinical
effect, as subjectively assessed by the treating anesthesiologist or
surgeon as improved clotting or stopped bleeding, and laboratory
parameters pre- and post-transfusion, were all documented in a
protocol, Appendix 1. The involved staff evaluated the logistics,
including time and work efforts, using a laboratory protocol,
Appendix 2. The transfused blood components and laboratory data
were collected from the laboratory systems.
Preparation, transportation, and thawing of
cryopreserved platelets
For cryopreservation, a total of 30 newly produced platelet units
derived from pooled buffy coats were transferred to a freezing bag
(Macopharma) using a sterile connection device (Terumo BCT,
Lakewood, CO, USA). A mixture of 25% DMSO/NaCl (50 ml) was
then sterile docked, and the solution was added to the platelet
concentrates. After centrifugation at 1,200 gfor 10 min, as much
supernatant as possible was removed, leaving 0.5 ml freezing medium
in ∼10 mL of platelets. The freezing bags, containing ∼10 ml
of platelet (5% DMSO), were immediately frozen in sheet metal
boxes using a fast-uncontrolled freezing rate protocol at −80◦C.
The frozen units were transported on dry ice to the receiving
hospitals using a transport courier and immediately placed in a low-
temperature freezer at −80◦C. When a platelet unit was requested,
the cryopreserved platelets were thawed in a thawing bath maintained
at 37◦C for 1 min. The thawed and cryopreserved platelets were then
sterile docked and gently reconstituted with compatible fresh thawed
plasma to a total volume of 200 ml. The platelet unit was resting,
non-agitated, until transfusion.
Laboratory parameters pre- and
post-transfusion
The hospital laboratories performed routine cell count and
coagulation tests, including fibrinogen (g/L) (Clauss coagulation
photometry), prothrombin time (PT) international normalized ratio
(INR), and activated partial thromboplastin time (APTT). Analysis
by thromboelastography (TEG) (Haemonetics Corp Boston, Mass.
USA) was performed during the study, but not used in routine in the
two small hospitals. ROTEM (GmbH, Leipzig, Germany) was used in
the largest hospital.
TABLE 1 Patient characteristics.
Included patients 23
Male/female 16/7
Age mean ±SD, min, max 64.6 ±14,3;
27,90
Diagnosis
Gastrointestinal bleeding 9
Trauma bleeding 4
Peroperative bleeding (hysterectomi, pancreactomi,
cholecystectomy+liver, liver, mesenterial)
5
Bleeding due to septicemia, DIC 2
Bleeding due to thrombocytopenia 2
Bleeding due to sinus thrombosis and anti-coagulant therapy 1
Statistical analyses
The mean values and standard deviation are given unless
otherwise indicated. A t-test was assessed to determine the statistical
significance of the differences in laboratory values pre- and post-
transfusion. The analyses were carried out using GraphPad Prism
version 9.0 (121) (GraphPad San Diego CA USA).
Ethics
The study was approved by the Swedish Regional Ethics
Review Boards Dno 2019-00350 and 2020-05579. Signed approval
was obtained from the participating centers. In accordance with
the ethical approval, informed consent was not required from
the patients.
Results
Included patients
The study included 23 bleeding patients over the course of
more than 2 years, as shown in Table 1. Nine patients (39%) were
treated for gastrointestinal bleeding, five (22%) for perioperative
bleeding, and four (17%) for trauma bleeding. Twelve (52%) of
the patients were included at the smallest hospital, where they
had no other platelets in stock, eight at the middle-sized hospital,
and three at the larger hospital joining the last period of the
study. Cryopreserved platelets were used on all bleeding patients
in the smallest hospital, during the study period. In the middle-
sized hospital, 518 platelet units were transfused during the study
period of which ∼130 units were to bleeding patients and the rest
to prophylactic transfusions to hematology and oncology patients.
Wastage of platelets, due to expiry, was close to 40% in this
hospital located on an island. The largest hospital participating in
the last 6 months of the study of interest to test the feasibility
of cryopreserved platelets as a backup stock included three of 22
bleeding patients.
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FIGURE 1
Cell count, concentration of coagulation factor, and viscoelastography properties pre- (Base) and post-treatment. Cell count, fibrinogen (g/L) (Clauss
coagulation photometry), prothrombin time (PT) international normalized ratio (INR), and activated partial thromboplastin time (APTT) analysis presented
pre-treatment and post-treatment of platelet transfusion. Bar graphs show mean ±SD for (n=) pre-treatment and post-treatment of platelet
transfusion. ns indicates non significant dierence compared to pre-treatment.
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FIGURE 2
Viscoelastography properties pre- (Base) and post-treatment. Thromboelastography (TEG) output for reaction rate (R) (min), kinetics time (K) (min), angle
(α) (degrees), maximum amplitude (MA) (mm), and functional fibrinogen (FF). Bar graphs show mean ±SD for n=4 pre-treatment and post-treatment of
platelet transfusion.
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TABLE 2 Outcome.
Blood transfusions
Red blood cells units mean ±SD; min,max
Plasma units mean ±SD; min,max
4.9 ±3.3; 0, 13
3.2 ±2.3; 0, 9
Platelet units total mean ±SD; min, max
Platelet units cryopreserved mean ±SD;min, max
1.9 ±2.2; 1, 11
1.5 ±1.2; 1, 6
Complications
Reoperation 1
Abscess
Transfusion reactions
Mortality
Length of stay mean ±SD; min, max
1
1
2
11.8 ±14.4; 1, 47
Laboratory data, blood transfusions, and
complications
In 6 of the 23 patients, the platelets were assessed to have
a visible effect (improved clotting or stopped bleeding), in nine,
there was no visible effect, and in eight, there was no comment
in the protocol by the treating clinician (Appendix 1). There was
no significant statistical difference in laboratory values, referring
to platelet count, fibrinogen, INR, APTT, and TEG (used in one
hospital) and ROTEM (used in one hospital, data not shown)
parameters, pre- and post-transfusion (Figures 1,2). The collection
of samples was not consistently done according to the protocol,
resulting in missing data. The time of the blood sampling in relation
to the transfusion of the platelet unit, other blood components, and
fibrinogen was unclear, making the laboratory results difficult to
interpret. Viscoelastic testing was not part of the normal routine in
the two smaller hospitals, and was then not at all used in the smallest
hospital and not consistently used in emergent situations in the other
hospital. In the largest hospital, ROTEM was used. The results from
viscoelastic testing were few and difficult to interpret for the same
reason as other laboratory analyses. In total, 14 of the 23 patients
were transfused with only one frozen platelet unit, six patients were
transfused with two frozen platelet units, two patients were also
treated with one unit of fresh platelets, and one trauma patient was
treated with five fresh and six frozen platelet units, in mixed order.
Two patients did not survive, one was transported to a university
hospital due to surgical complications and died there, and one died
in septic shock. The transfusion needs were 4.9 ±3.3 red blood cell
units, 3.2 ±2.3 plasma units, and 1.9 ±2.2 platelet units, whereof
cryopreserved were 1.5 ±1.1 (mean ±SD) (Table 2). There was a
mild allergic reaction in one patient, possibly due to the plasma unit.
No other complications associated with the platelet transfusions were
seen. The length of stay in the hospital was 11.8 ±14.4 (mean ±SD),
with a range of 1–46 days.
Storage and logistics
The mean time from the order of platelets to transfusion was
64 min, with a range from 25 to 180 min (Table 3). In the two
rural hospitals in our study, there was only one biomedical scientist
working night and weekends, responsible for all laboratory analyses
and blood product requests, that is, blood counts, coagulation
TABLE 3 Clinical eect and logistics.
Clinical opinion
Visible effect 6
No visible effect
No comment
9
8
Logistics time from order to delivery (min)
mean ±SD; min, max 66.0 ±37.2; 25, 180
tests, blood type, and type and screen, as well as requested blood
units, in bleeding patients. After initial training and practice, the
opinion was that the procedure to prepare the cryopreserved platelets
was simple. Tested with trained personnel, the procedure was
done in <15 min, provided thawed plasma is available. If platelets
are not locally available, the transport of fresh platelets to the
smallest hospital in the study is ∼2 h from the time of order.
To the hospital on the island, transport is often not possible for
many hours and is available only in the daytime. Cryopreserved
platelets stored locally can be transfused within 30–60 min from
the order.
Discussion
In this study, in three remote hospitals, we show the feasibility
of using cryopreserved platelets in the treatment of bleeding. The
primary aim of the study was to evaluate the logistics of using
cryopreserved platelets in acute bleeding, and the secondary aims
were to assess indications and clinical effects. The preparation of the
cryopreserved platelets and distribution on dry ice from a university
hospital to the receiving hospital and the local storage in a −80◦C
freezer were performed without difficulties. For the local preparation
of the platelet units, the staff needs training and instructions, and
the time from request to transfusion varied between 25 and 180 min
in the study, but with trained personnel, it is done in 15–30 min.
The indications for platelet transfusions can vary depending on the
level of healthcare offered in hospitals, and in our study reflecting
general care, the indications were due to gastrointestinal bleeding,
complications in elective surgery, and trauma, which are probably
representative of smaller hospitals. Two of the hospitals have also
obstetric wards, but no obstetric patients were included during
the study period. We could not show the difference in laboratory
values pre- and post-transfusion, after transfusion of one to two
platelet units in bleeding patients, which was expected. Samples
were not collected consistently pre- and post-transfusion, and the
administration of red blood cells, plasma, and fibrinogen in relation
to blood sampling was not documented, making the results difficult
to interpret. The clinical assessment was that the platelets were
hemostatic, supported by an adequate ratio of platelets to red cells
and plasma before bleeding was controlled. No one died of bleeding.
There was one mild allergic reaction, and no other adverse reactions
were seen, supporting previously published data on safety. The
inclusion of patients was slower than expected and the planned
protocol was often violated, resulting in missing data and reflecting
the challenges with research studies in small hospitals with limited
staff resources and rotating physicians. Despite that, the subjective
opinion from the clinicians was that the cryopreserved platelets
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were hemostatic and offered an increased therapeutical arsenal and
redundancy at the hospital.
Platelets are important in the treatment of bleeding but are often
not available or of insufficient supply in many rural hospitals in our
country as well as other countries and thus bleeding patients may
not be optimally treated (2,21). Initially, we included patients in
two remote hospitals. One of the hospitals has normally no platelets
in stock, due to high wastage and high costs. The annual usage is
estimated to be 10–20 platelet units, the majority was prophylactic
transfusions. Transport time of platelets is 2 h from the nearest
larger hospital. The other hospital is located on an island in the
Baltic Sea, with challenging transportation. The hospital has normally
2–4 platelet units in stock, resulting in ∼40% wastage but often
deficiency in acute bleeding situations. A third regional hospital
expressed interest to participate and evaluate cryopreserved platelets
as a backup to a normal stock of 10 units, which may be important in
mass causality situations.
The quality and in vitro function of cryopreserved platelets have
been extensively studied by us and others, in many publications
(10,11,15). The platelets are activated and affected in the freezing and
thawing procedures, but still contain adequate hemostasis function
when measured by viscoelastography (13,15). Cryopreserved
platelets have been used clinically on special indications since the
1970s (9). In an early clinical study by Khuri et al. from 1999,
where bleeding patients were randomized to either cryopreserved or
standard platelets, the conclusion was that cryopreserved platelets
were superior to liquid platelets in reducing blood loss and the
need for blood transfusions (18). Despite the promising results,
cryopreserved platelets have not been widely implemented, but
recently, there is a growing interest both for military use and in
remote hospitals where transportation and logistics are complicated.
Until now many hundreds of cryopreserved platelet units have been
transfused with safe results (20). There is no increased incidence of
adverse reactions shown. The final results from ongoing prospective
randomized clinical trials in Australia and New Zealand addressing
non-inferiority to standard platelets will be important (19,20).
Limitations of this study include the study being done in small
hospitals with limited staff resources and a limited number of
bleeding patients. The initial aim included laboratory analyses pre-
and post-transfusion, which often were missed. Analysis by TEG was
offered but not used in one of the hospitals and rarely in the other. We
were careful not to delay platelet transfusions to bleeding patients, so
there were no recommendations to prioritize cryopreserved platelets
more than in the hospital where no other platelets were available.
Patients were included based on the availability of fresh platelets,
which were often prioritized, by the working clinicians, In addition,
the information of the study to deputy clinicians, common in
rural hospitals, was often insufficient. Thus, the clinical effects of
cryopreserved platelets cannot be evaluated from our study, but
nothing is contradicting previous results reporting effect and safety
(9,17,18,20), from larger studies.
We conclude that cryopreserved platelets in remote hospitals are
feasible and that cryopreserved-thawed platelets may theoretically be
transfused within 30 min and were most often transfused in an hour
in our small study. The ability to have platelets in stock increases
the safety for bleeding patients, where the alternative may be delayed
treatment with many hours of transport of platelets from a larger
hospital. In addition, cryopreserved platelets can be used as a backup
stock in larger hospitals, e.g., during long weekends when it is difficult
to predict the need, in mass causality situations, and in military
preparedness. There is potential to further improve the freezing and
thawing procedures and to increase the storage time from today’s
1 to 4 years to a longer time, that is, 12 years reported in a recent
study (8). Our study describes the logistics of using cryopreserved
platelets in small remote hospitals and supports the potential
of having platelets available in all hospitals occasionally treating
bleeding patients. However, preparation and thawing procedures can
be further improved, and additional studies of in vitro and in vivo
performance of cryopreserved platelets are warranted.
Data availability statement
The original contributions presented in the study are included in
the article/Supplementary material, further inquiries can be directed
to the corresponding author.
Ethics statement
The studies involving human participants were reviewed and
approved by Swedish Regional Ethics Review Boards nos. 2019-00350
and 2020-05579. Written informed consent for participation was not
required for this study in accordance with the national legislation and
the institutional requirements.
Author contributions
AW, LÖ, KB, HS, and P-OF designed the study. LÖ, KB, HS,
A-MH, and RH included the patients. BD, PH, and P-OF supported
the logistics in the lab. PS produced the cryopreserved platelets. AW
and PS wrote the first draft of the manuscript. All authors contributed
to the writing and approved the final version of the manuscript.
Funding
The study was funded by ALF grant (no. 510751) from the region
of Stockholm and the Swedish Armed Forces Science and Technology
fund (no. AT9221011).
Acknowledgments
Warm thanks to the staff at Visby Hospital, Torsby Hospital,
and Karlstad Hospital, and especially to Marie Stenberg, Karin Holst,
Helena Lindberg, and Marita Bengtsson.
Conflict of interest
The authors declare that the research was conducted in the
absence of any commercial or financial relationships that could be
construed as a potential conflict of interest.
Publisher’s note
All claims expressed in this article are solely those
of the authors and do not necessarily represent those of
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Wikman et al. 10.3389/fpubh.2022.1073318
their affiliated organizations, or those of the publisher,
the editors and the reviewers. Any product that may be
evaluated in this article, or claim that may be made by
its manufacturer, is not guaranteed or endorsed by the
publisher.
Supplementary material
The Supplementary Material for this article can be found
online at: https://www.frontiersin.org/articles/10.3389/fpubh.2022.
1073318/full#supplementary-material
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