Cold-Stored vs Room Temperature Platelets for Cardiac Surgery

(PLTS-1 Trial)

Recruiting at 1 trial location

Overseen By Deep Grewal

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University Health Network, Toronto

Must not be taking: Warfarin, Antiplatelets, Direct oral anticoagulants

Disqualifiers: Hemostatic disorders, Pregnancy, Hemodynamic instability, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 1 day

150 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before surgery. You must not be on warfarin or direct oral anticoagulants within 3 days prior to surgery, and you must not take antiplatelet drugs (except aspirin) within 5 days prior to surgery.

What data supports the effectiveness of the treatment Delayed Cold-Stored Buffy Coat Platelets in cardiac surgery?

Research suggests that cold-stored platelets may have better blood-clotting properties compared to room temperature platelets, which could be beneficial in surgeries like cardiac surgery. Additionally, cold storage may extend the shelf life of platelets, making them more available for use. ^{1 2 3 4 5}

Is it safe to use cold-stored or room temperature platelets in humans?

Research suggests that both cold-stored and room temperature platelets have been used in humans, with cold-stored platelets potentially having a shorter survival time in the body compared to room temperature platelets. However, both types have been studied in healthy volunteers and used in cardiac surgery, indicating they are generally considered safe for human use. ^{1 3 6 7 8}

How is the treatment of cold-stored vs room temperature platelets for cardiac surgery different from other treatments?

This treatment is unique because it involves storing platelets at cold temperatures (1-6°C) instead of the standard room temperature (20-24°C), which may extend their shelf life and improve their ability to stop bleeding during cardiac surgery. ^{1 2 4 9 10}

What is the purpose of this trial?

PLTS-1 is a multicentre, randomized, controlled, pilot trial, using a conventional, parallel group, two-armed design at 2 cardiac surgery centres in Canada. The study is designed to assess the feasibility of a future, definitive RCT to determine the non-inferiority of cold-stored platelets compared to conventional platelets with respect to hemostatic effectiveness (total number of allogeneic blood products transfused within 24 hours after CPB), as well as safety.

Research Team

Jeannie Callum, MD

Principal Investigator

Queen's University

Justyna Bartoszko, MD

Principal Investigator

University Health Network, Toronto

Eligibility Criteria

This trial is for adults over 18 who need elective cardiac surgery with CPB (heart-lung machine support). It's specifically for those at high risk of bleeding, like patients with low platelet counts or undergoing complex surgeries such as multiple valve repairs or aorta replacement.

Inclusion Criteria

I am scheduled for complex surgery or have a low platelet count.

I have had a complex heart surgery involving valves or aorta.

I am 18 or older and scheduled for heart surgery with a heart-lung machine.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either cold-stored or room temperature-stored platelets during cardiac surgery

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Treatment Details

Interventions

• Delayed Cold-Stored Buffy Coat Platelets
• Room Temperature Buffy Coat Platelets

Trial Overview The PLTS-1 study compares two types of platelet storage methods: cold-stored and room temperature. The goal is to see if cold-stored platelets are just as good at preventing bleeding after heart surgery using CPB as the standard room temp stored ones.

Participant Groups

Group I: Intervention Group Experimental Treatment 1 Intervention

Patients randomized to the Delayed Cold-Stored Platelet Group will receive ABO-identical buffy-coat platelets (pathogen reduced products) maintained at 22°C for up to 4 days then placed at 4°C for a minimum of 1 day (24 hours), with expiration at 14 days after collection.

Group II: Control Group Active Control 1 Intervention

Those randomized to the Room Temperature Platelet Group will receive ABO-identical buffy-coat platelets (pathogen reduced products) maintained at 22°C for up to 7 days (as per current standard of care).

Delayed Cold-Stored Buffy Coat Platelets is already approved in United States, Canada for the following indications:

Approved in United States as Cold-Stored Platelets for:

• Trauma patients with hemorrhagic shock
• Cardiac surgical patients with acute bleeding

Approved in Canada as Cold-Stored Platelets for:

• Cardiac surgical patients with acute bleeding

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Queen's University

Collaborator

Trials

382

Recruited

122,000+

Canadian Blood Services

Collaborator

Trials

24

Recruited

39,200+

Queen's University

Collaborator

Kingston Health Sciences Centre

Collaborator

Trials

312

Recruited

112,000+

Findings from Research

In a study of 713 adults undergoing cardiac surgery, delayed cold-stored platelets were linked to higher rates of postoperative transfusions compared to room temperature-stored platelets, with 44% of patients receiving delayed cold-stored platelets requiring additional transfusions within the first 24 hours.

Despite the increased transfusion rates, there were no significant differences in clinical outcomes such as reoperation for bleeding or chest tube output, suggesting that while delayed cold-stored platelets can be used in critical situations, they may not be the best first choice for transfusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative Transfusions after Administration of Delayed Cold-stored Platelets versus Room Temperature Platelets in Cardiac Surgery: A Retrospective Cohort Study. Klompas, AM., Zec, S., Hanson, AC., et al.[2023]

Cold-stored platelets (CSP) have been shown to maintain better hemostatic function and adhesion properties compared to standard room-temperature platelets (RTP), making them potentially more effective for patients undergoing cardiac surgery.

CSP also offer advantages such as a longer shelf-life and a lower risk of bacterial contamination, but further large clinical trials are necessary to confirm their benefits in treating acute bleeding situations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cold-stored platelets for acute bleeding in cardiac surgical patients: a narrative review. Lu, J., Karkouti, K., Peer, M., et al.[2023]

Buffy coats (BCs) stored in containers with low gas permeability showed significant accumulation of CO2 and a rapid decrease in pH, which can negatively affect the quality of platelet concentrates (PCs).

Continuous mixing during storage led to increased red cell damage without clear benefits, suggesting that BCs should ideally be stored for 24 hours or less to maintain platelet viability and minimize activation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Storage of buffy coat preparations at 22 degrees C in plastic containers with different gas permeability. Eriksson, L., Eriksson, G., Högman, CF.[2019]

Cold-stored platelets can be stored for up to 20 days, showing better preservation of certain platelet functions compared to standard room temperature-stored platelets, particularly in terms of integrin activation and mitochondrial integrity.

However, platelet recovery declines significantly after 10 days of cold storage, indicating that while cold storage may extend shelf life, its effectiveness in clinical applications still needs to be validated in bleeding patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of storage time prolongation on in vivo and in vitro characteristics of 4°C-stored platelets. Stolla, M., Bailey, SL., Fang, L., et al.[2020]

Cold-stored platelets (CS-PLTs) were approved for use in actively bleeding trauma patients, with initial FDA approval for a 3-day storage period without agitation, highlighting their potential for improved hemostatic outcomes compared to room temperature platelets.

Despite the approval, a high discard rate of 80.9% was observed due to clot formation during storage, indicating a need for advancements like pathogen-reduced solutions to extend shelf life and reduce contamination risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cold platelets for trauma-associated bleeding: regulatory approval, accreditation approval, and practice implementation-just the "tip of the iceberg". Stubbs, JR., Tran, SA., Emery, RL., et al.[2018]

Platelet concentrates prepared from buffy coats stored at 4 degrees C showed significantly lower recovery and survival rates in vivo compared to those from platelet-rich plasma stored at 22 degrees C, with recovery rates of 30.5% vs. 41.4% and survival times of 2.4 days vs. 7.0 days, respectively.

The study involved 8 healthy volunteers and highlights the importance of storage temperature for optimizing the efficacy of platelet concentrates, suggesting that storage at 22 degrees C is preferable for better platelet survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival in vivo of platelets stored for 48 hours in the buffycoat at 4 degrees C compared to platelet rich plasma stored at 22 degrees C. Pietersz, RN., Loos, JA., Reesink, HW.[2019]

Storing buffy coats overnight at room temperature results in a higher platelet yield and white blood cell count compared to fresh buffy coats held for only 2 hours, indicating a potential advantage for platelet concentrate production.

However, the overnight storage also leads to increased levels of lactate and LDH, suggesting that while the yield is higher, there may be some storage-related changes that could affect the quality of the platelets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative analysis of platelet concentrates prepared after two hours and overnight storage of buffy coat at room temperature. Ojha, S., Tirlotkar, A., Gupta, AM., et al.[2021]

Platelet concentrates (PCs) prepared from buffy coats (BCs) held at room temperature for up to 12 hours maintain their quality for up to 5 days in plasma, showing no detrimental effects on key quality indicators like pH and morphology.

Extending the holding time from 3 to 12 hours improved the preservation of platelet activation markers and enhanced thrombin-induced aggregation, suggesting that longer holding times can be beneficial for platelet function without compromising safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of a 12-hour, 22 degrees C holding period for buffy coats on the preparation of platelet concentrates stored in plasma. Boeri, N., Saleun, S., Pelissier, E., et al.[2019]

Cold-stored platelets and delayed-cold platelets (stored at room temperature for 4 days before refrigeration) maintained similar platelet counts and activation profiles over a 21-day period, indicating that delayed-cold storage could be a practical alternative.

Transferring platelets to refrigerated storage near their expiry date may help maximize platelet inventories without compromising their quality, making it a potential strategy for managing platelet supplies effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maximising platelet availability by delaying cold storage. Wood, B., Johnson, L., Hyland, RA., et al.[2019]

Platelet concentrates (PCs) made from overnight-stored buffy coats showed similar platelet yield to those made from fresh blood, suggesting they could be effectively used in clinical settings.

Stored PCs from overnight-stored buffy coats demonstrated better aggregation at lower temperatures (25 degrees C) compared to higher temperatures (37 degrees C), indicating potential advantages in storage conditions for maintaining platelet function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Storage of platelet concentrates from overnight-stored blood and overnight-stored buffy coat: in vitro studies. Rácz, Z., Baróti, C.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Postoperative Transfusions after Administration of Delayed Cold-stored Platelets versus Room Temperature Platelets in Cardiac Surgery: A Retrospective Cohort Study. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Cold-stored platelets for acute bleeding in cardiac surgical patients: a narrative review. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Storage of buffy coat preparations at 22 degrees C in plastic containers with different gas permeability. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Effects of storage time prolongation on in vivo and in vitro characteristics of 4°C-stored platelets. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Cold platelets for trauma-associated bleeding: regulatory approval, accreditation approval, and practice implementation-just the "tip of the iceberg". [2018]

6. Germany pubmed.ncbi.nlm.nih.gov

Survival in vivo of platelets stored for 48 hours in the buffycoat at 4 degrees C compared to platelet rich plasma stored at 22 degrees C. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Comparative analysis of platelet concentrates prepared after two hours and overnight storage of buffy coat at room temperature. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Influence of a 12-hour, 22 degrees C holding period for buffy coats on the preparation of platelet concentrates stored in plasma. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Maximising platelet availability by delaying cold storage. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Storage of platelet concentrates from overnight-stored blood and overnight-stored buffy coat: in vitro studies. [2019]