Study reference 

Study characteristics 

Patient characteristics  

Intervention (I) 

Comparison / control (C)  

Follow-up 

Outcome measures and effect size  

Comments 

McGuinness, 2022 

Type of study: pilot RCT 

Setting and country: double-blind, parallel group, single center pilot trial, New Zealand. 

Funding and conflicts of interest: the authors declare no conflicts of interest.  

Inclusion criteria: 

Cardiac surgery patients at high risk of platelet transfusion identified using the TRUST score. 

Exclusion criteria: 

Patients who received a platelet transfusion earlier during that hospital admission, women of childbearing age (to avoid the risk of rhesus immunization), when death was deemed inevitable in <24 hours (as mortality was a study end point), patients who had been enrolled previously in this study or in a clinical trial of a medication (with the exception of aspirin) thought to influence bleeding, patients with a known bleeding diathesis associated with abnormal clotting on investivations taken immediately preoperatively, patients who object to receipt of human blood products, patients with intellectual impairment making them unable to consent to surgery, or if their treating clinician believed participation was not in their best interest. 

N total at baseline: 

Intervention: 10 

Control: 13 

Important prognostic factors2: 

age (mean IQR) 

I: 69 (59 – 77) 

C: 73 (64-77) 

Sex:  

I: 90% M 

C: 38.5% M 

Groups comparable at baseline? Between-group baseline imbalances were seen in sex, weight and incidence 

of diabetes (Table 1). Intraoperative complexity was equivalent 

(Table S1). 

Describe intervention (treatment/procedure/test): 

Cryopreserved platelets 

When required for transfusion, the platelet–plasma unit is placed in a 37 °C water bath until reaching a temperature of 30 °C, at which point the plasma is gently mixed with the platelets to disperse 

any clumps. Reconstituted cryopreserved platelets contain more than 40% of the platelets in the original component, and have a 6-h shelf life. 

Describe  control (treatment/procedure/test): 

Patients randomized to receive liquid-stored platelets were transfused 

leucocyte-depleted apheresis or pooled whole-blood derived platelets in either additive solution or plasma, according to the available supply. The hospital blood bank selected the ABO and Rh group 

according to its standard practice. 

Length of follow-up: 

28-days 

Loss-to-follow-up: 

No patients were lost to follow-up.  

One patient randomized to liquid-stored platelets was transfused one unit of open-label (liquid stored) platelets before subsequently 

receiving 3 units of study platelets. This patient was 

retained in the intention-to-treat analysis as part of the liquid-stored platelet group. 

Incomplete outcome data:  

Not reported.  

Outcome measures and effect size (include 95%CI and p-value if available): 

Blood loss 

There were no differences in the median intra- or postoperative blood 

loss between study groups up to 48 h (Figure 3 and Table S2). 

Transfusion requirement 

There were no significant differences in the quantities of blood components transfused. 

Complications (adverse events) 

There were no pro-thrombotic arterial or venous complications, 

including acute myocardial infarction, in either study group. No adverse events were reported to the Data and Safety Monitoring 

Committee (DSMC). 

Mortality 

Two patients in the 

cryopreserved platelet group, but none in the liquid-stored group, had died by 28-days postoperatively. 

Conclusion 

This pilot randomized controlled trial demonstrated the feasibility of the 

protocol and adds to accumulating data supporting the safety of this intervention. 

Given the clear advantage of prolonged shelf-life, particularly for regional hospitals in New Zealand, a definitive non-inferiority phase III trial is warranted. 

Limitations 

Finally, transfusion of a unit of cryopreserved platelets was 

accompanied by the mandatory transfusion of plasma (109 ml) in which 

the platelets were resuspended. The trial could, therefore, be a comparisonof platelets plus plasma versus platelets alone. 

Strandenes, 2020 

Type of study: pilot RCT 

Setting and country: single center two-stage pilot RCT, Norway 

Funding and conflicts of interest: Dr. Spinella reports ongoing financial relationships with Secure Transfusion Services (South San Francisco, California), 

Cerus (Concord, California), Entegrion (Durham, North 

Carolina), KaloCyte (Baltimore, Maryland), and Haima 

(Cleveland, Ohio), and a past financial relationship with 

Hemanext (Lexington, Massachusetts). The opinion or assertions 

contained herein are the private views of the authors and 

are not to be construed as official or as reflecting the views of the U.S. Department of the Army, the U.S. Department of Defense or the Norwegian Armed Forces Medical Services. 

The remaining authors declare no competing interests. 

Inclusion criteria: 

The inclusion screening criteria were scheduled 

elective or semiurgent cardiothoracic surgery with either 

expected CPB time over 120 min or use of dual platelet 

inhibition drugs less than 48 h before surgery. 

Informed consent was obtained from patients who fulfilled the screening criteria; however, only the subset of consented patients who developed indications for platelet 

transfusion and had orders for study platelets received by 

the blood bank were enrolled into the study. 

Exclusion criteria: 

Patients with 

congenital coagulopathies or hemostatic disorders were 

ineligible. 

N total at baseline: 

Intervention: 25 

Control: 25 

Important prognostic factors2: 

age ± SD: 

I: 65 (57-71) 

C: 61 (46-67) 

Sex:  

I: 68% M 

C: 64% M 

Groups comparable at baseline? Yes 

Describe intervention (treatment/procedure/test): 

Cold-stored platelets (2°C to 6°C). Stored for up to 7 days. 

Describe  control (treatment/procedure/test): 

Platelets stored at room temperature (20°C to 24°C). Stored for up to 7 days. 

Length of follow-up: 

28 days. 

Loss-to-follow-up: 

Not reported. 

Incomplete outcome data:  

Intervention: 

4 patients were excluded (2 reoperation, 1 iatrogenic spleen bleeding, 1 transfused pooled buffycoat platelets). 

Control:  

4 patients were excluded (1 reoperation, 1 transfused incorrectly processes platelets, 2 transfused room-temperature stored platelets instead of cold-stored platelets. 

Outcome measures and effect size (include 95%CI and p-value if available): 

Blood loss 

As shown in figure 2, postoperative blood loss measured as median chest drain output was 720 ml (485 to 1,170, 180 to 2,340) for room temperature, 645 ml (460 to 800, 90 to 1,785) for cold-stored up to 7 days. 

In the post hoc analysis, the median chest drain output was 720 ml (490 to 1,020, 180 to 2,340), and 590 ml (450 to 720, 90 to 960), for room temperature, cold storage for up to 7 days. 

The difference in medians between the room temperature and cold-stored up to 7 days arm was 75 ml (95% CI, -220, 425). 

Blood product usage 

There were no statistically 

significant differences in total units of transfused platelets 

(P = 0.124), plasma (P = 0.079), or red cells (P = 0.543) in the room temperature– and cold-stored up to 7 days arms. 

Fibrinogen: 

I: 11 (44%) 

C: 15 (60%) 

Prothrombin: 

I: 4 (16%) 

C: 2 (8%)  

Platelet function 

Platelet count increased after 

platelet transfusion for all study arms (P < 0.05).  

Multiple electrode aggregation response to all agonists increased after platelet transfusion for all study arms (P < 0.05). 

Median thromboelastography 

Maximum amplitude 

remained within normal ranges in all study arms 

Adverse events 

No transfusion reactions related to platelet transfusions 

were observed. 

Mortality 

Overall 28-day hospital mortality of three deaths (12%) in the room temperature group, two (8%) in the cold-stored 

7 days arm.  

Length of stay 

For the evaluation of length of stay in intensive care, one patient in the room 

temperature arm, two patients in the cold-stored up to 7 days arm, and two patients in the cold-stored for 8 to 14 days arm remained in intensive care at the conclusion of the 

28-day study period. 

Trombose (arterial + venous) 

I: 6 

C: 8 

Conclusion 

This pilot trial supports the feasibility of platelets stored cold for up to 14 days and provides critical guidance for future pivotal trials in high-risk cardiothoracic bleeding patients. 

Limitations 

Most patients received the first transfusion episode 

during surgical hemostasis when multiple blood components and hemostatic products were transfused simultaneously.This might influence results. 

The number of patients 

having previous sternotomies was higher in the cold-stored 

up to 7 days arm. History of previous sternotomies is associated with increased bleeding and might influence the results; especially chest drain output and blood product use. 

Fase II: cold-stored platelets for 8 to 14 days. 15 patients were included.  

Reade, 2019 

Type of study: pilot RCT 

Setting and country: double-blind, parallel-group, standard-care controlled multicenter pilot trial conducted in four Australian tertiary academic hospitals  

Funding and conflicts of interest: The authors have disclosed no conflicts of interest. 

Inclusion criteria: 

Adult patients (aged 18 years) were eligible for the study if they 

were scheduled to undergo cardiac surgery and at least three of the TRUST criteria (which predict a high risk of red blood cell 

[RBC] transfusion) were present. 

Exclusion criteria: 

Patients were excluded if they had received a PLT 

transfusion earlier during the same hospital admission; if they were women of childbearing age (18-55 years); if death was deemed inevitable in less than 24 hours; if they had been previously enrolled in this study or a clinical trial of a 

medication (with the exception of aspirin) or technique thought to influence bleeding; if they had a known bleeding 

diathesis (for example, hemophilia or Von Willebrand disease)or hematologic malignancy associated with abnormal clotting on blood investigations taken in the immediate pre 

operative 

period (i.e., PLT count <100 X10^3 

international 

normalized ratio >1.5, activated partial thromboplastin time >1.5× upper limit of normal); if they had a known allergy to DMSO; if they had a known objection to receipt of human blood products; if they had intellectual impairment such 

that they were unable to consent for surgery themselves; or 

if their treating physician believed that it was not in their best interest to participate in the trial. 

N total at baseline: 

Intervention: 23 

Control: 18 

Important prognostic factors2: 

age ± SD: 

I: 71 (66-77) 

C: 70 (65-75) 

Sex:  

I: 70% M 

C: 67% M 

Groups comparable at baseline? Study groups were generally well balanced at baseline. 

Describe intervention (treatment/procedure/test): 

Cryopreserved platelets 

In the hospital blood bank, 

cryopreserved PLTs were thawed in a water bath at 37C and reconstituted using AB or group-specific plasma either thawed 

specifically for the purpose or maintained prethawed for emergencies. 

Plasma was transferred to the PLT bag using sterile tubing inserted into the access port. PLTs could be transfused up to 4 hours after reconstitution. 

Describe  control (treatment/procedure/test): 

Liquid stored platelets. 

Patients randomized to receive liquid-stored PLTs were transfused pooled buffy coat PLTs or (if a suitable buffy coat 

PLT unit was unavailable) apheresis PLTs prepared by the ARCBS and distributed to hospital blood banks according to routine practice. The hospital blood bank selected the PLT 

ABO group to be infused according to its standard practice. 

Length of follow-up: 

28 days 

Loss-to-follow-up: 

No patients were lost to follow-up. 

Incomplete outcome data:  

Intervention: 

3 patients received open-label platelets before 3 study platelet units. 

Control: none. 

Outcome measures and effect size (include 95%CI and p-value if available): 

Blood loss 

There were no differences in any measure of intra- or post 

operative blood loss (Table 3 and Fig. 2). 

Blood products used 

There were several differences in quantities of blood 

products transfused between the groups (Table 4). Whole 

blood was not available for use during the study. RBC transfusion was not different, 

although numerically fewer 

patients in the cryopreserved group were transfused in the 

OR and were transfused one fewer unit overall. Patients in 

the cryopreserved group were significantly more likely to be 

transfused FFP, and overall a greater median volume of FFP 

was transfused to this group. However, among only those 

patients transfused FFP, the median number of FFP units 

was not different. Patients in the cryopreserved group 

received a median of 1 more unit of study PLTs. Very few 

patients received nonstudy open-label PLT transfusions, 

and this did not differ between groups. The only difference 

in laboratory variables the day after surgery was the PLT 

count, which was significantly lower in the cryopreserved 

PLT group (Table 5). 

Adverse events 

No transfusion reactions related to platelet transfusions 

were observed. 

Mortality 

None of the patients died. 

Hospital length of stay 

I: 18 (10-28) days 

C: 23 (16-34) days 

Study reference 

(first author, publication year) 

Was the allocation sequence adequately generated? 

Definitely yes 

Probably yes 

Probably no 

Definitely no 

Was the allocation adequately concealed? 

Definitely yes 

Probably yes 

Probably no 

Definitely no 

Blinding: Was knowledge of the allocated 

interventions adequately prevented? 

Definitely yes 

Probably yes 

Probably no 

Definitely no 

Was loss to follow-up (missing outcome data) infrequent? 

Definitely yes 

Probably yes 

Probably no 

Definitely no 

Are reports of the study free of selective outcome reporting? 

Definitely yes 

Probably yes 

Probably no 

Definitely no 

Was the study apparently free of other problems that could put it at a risk of bias? 

Definitely yes 

Probably yes 

Probably no 

Definitely no 

Overall risk of bias 

If applicable/necessary, per outcome measure 

LOW 

Some concerns 

HIGH 

McGuinness, 2022 

Definitely yes; 

Reason: Patients were 

Randomly allocated 

1:1 to study groups 

Using computer-generated permuted block randomization 

Unclear; 

Reason: No more details about the randomization process are presented in the paper.  

Definitely no; 

Reason: Clinicians in our trial were blinded using an opaque shroud that could be removed easily. 

This shroud was temporarily removed by a clinician not involved in the 

care of the patient to facilitate correct patient identification prior to transfusion. 

Blinding of patients, data collectors, outcome assessors, and data analysts is not reported.  

Definitely yes; 

Reason: no patients were lost to follow-up.  

Definitely yes; 

Reason: All relevant outcomes were reported;  

Definitely no; 

Reason: The major limitation of the trial is its small size, also because it is a pilot RCT. 

High risk of bias (all outcomes) 

Reason: due to the very limited sample size and because it is a pilot RCT. 

Strandenes, 2020 

Definitely yes; 

Reason: The study weeks were randomized to maintain an inventory for the study without excessive waste. A randomization 

list for study weeks was generated by use of electronic software. 

Definitely yes; 

Reason: The randomization list was only available to study co-workers at the Department of Immunology 

and Transfusion Medicine. Surgeons screening the patients 

for eligibility were blinded to the randomization, as were 

the clinical personnel responsible for the treatment and follow 

up of the patients. Clinicians were blinded to patient 

randomization when deciding whether to transfuse and 

when ordering platelets. 

Definitely no; 

Reason: Study coworkers from the Department 

of Immunology and Transfusion Medicine who obtained 

written informed consent, collected data from electronic 

medical records, and registered information in the study 

database were not blinded. 

Definitely yes; 

Reason: a few patients were excluded in the post-hoc analyses. Reasons are given and are similar between the groups.  

Definitely yes; 

Reason: All relevant outcomes were reported;  

Definitely no; 

Reason: The major limitation of the trial is its small size, also because it is a pilot RCT. A formal sample size calculation was not performed.  

High risk of bias (all outcomes) 

Reason: due to the very limited sample size and because it is a pilot RCT. 

Reade, 2019 

Definitely yes; 

Reason: Patients were randomized 1:1, stratified by site, using computer 

generatedpermuted block randomization. 

Unclear; 

Reason: No more details about the randomization process are presented in the paper.  

Probably yes; 

Reason: When a PLT transfusion was ordered, an unblinded blood bank scientist supplied study PLT units to operating room (OR) or ward staff. 

Study PLTs were supplied with 

an opaque shroud that obscured the storage method. 

Definitely yes; 

Reason: none of the patients were lost to follow-up.  

Definitely yes; 

Reason: All relevant outcomes were reported;  

Definitely no; 

Reason: The major limitation of the trial is its small size, also because it is a pilot RCT. Sample size was not calculated.  

High risk of bias (all outcomes) 

Reason: due to the very limited sample size and because it is a pilot RCT.