AABB24: CLIP-II Trial Examines Cryopreserved Platelets

One of the many challenges in transfusion medicine is the short lifespan of platelets stored at room temperature. At the Saturday afternoon session, “Cryopreserved Platelets: From Bench to Bedside,” AABB meeting attendees heard the first report from investigators involved in the Cryopreserved vs. Liquid Platelets (CLIP-II) trial. CLIP-II was a phase III multicenter, blinded, randomized, controlled, clinical non-inferiority trial. The study compared cryopreserved platelets vs. conventional liquid-stored platelets for the management of surgical bleeding. Other settings for platelet transfusion were also included in the trial. Both speakers at the Saturday session were among the study investigators.

Cryopreservation of Platelets—Why and How
First to present was Denese Marks, PhD, from the Australian Red Cross Lifeblood in Alexandria, NSW, Australia. She reviewed the impact of platelet insecurity and how cryopreservation of platelets might mitigate those impacts. Marks also explained the platelet cryopreservation process, which involves the following steps:

•    Collection by apheresis
•    Addition of DMSO
•    Centrifugation
•    Removal of supernatant
•    Resuspension
•    Vacuum packing
•    Freezing at –80 C
•    Shipping in protective container/carrier

Marks also described the thawing process (at 37 C for platelets and plasma separately, agitation at room temperature for 15 minutes for both bags separately, and then reconstitution of both together). She detailed post-thaw platelet damage and recovery as well.

Changes in Functionality and Use
Marks also noted that the CLIP-II Trial results showed changes in platelet functionality. Some effects represented increases in platelet properties, while other effects indicated decreases in platelet properties. She pointed out current uses of cryopreserved platelets including the following:

•    Civilian. Autologous platelets to support thrombocytopenic patients undergoing chemotherapy. Ten years of data showed that platelet increments were achieved.
•    Military. Casualty care in Afghanistan with cryopreserved platelets. No adverse effects were experienced and patients who needed massive transfusion had a lower death rate if cryopreserved platelets were used.

Economic Considerations
Of course, costs for any treatment must be in balance with the benefits. Marks identified potential reasons why a blood provider or a hospital may not benefit from the introduction of a cryopreserved platelet inventory. Some of the considerations include the following:

•    Clinical-grade DMSO
•    Equipment for processing and testing
•    Plasma for reconstitution
•    Trained staff
•    A –80 C freezer for storage

In her concluding comments, Marks noted that costs of providing and administering cryopreserved platelets are incurred by both the blood supplier and the hospital end user.

CLIP-II Trial Collaboration and Methods
The session continued with a discussion of the CLIP-II trial results, presented by Michael Reade, MBBS, MPH, DPhil, DMedSc from the University of Queensland Medical School, Brisbane, QLD, Australia. Reade, the principal investigator for the study, noted its collaborative nature—involving participation by the Australian and New Zealand Intensive Care Society Clinical Trails Group, the Australian and New Zealand College of Anaesthesiologists Clinical Trials Network, the Australasian Society of Cardiac and Thoracic Surgeons, the Australian Red Cross and the New Zealand Red Cross.

Reade shared with the session attendees basic data about the CLIP Trial. The study involved 388 cardiac surgery patients in 11 Australian hospitals from August 2021 to April 2024. Patients were to receive up to 3 units of either Group O cryopreserved platelets or conventional liquid-stored platelets if their clinicians determined that platelet transfusion was needed either intraoperatively or within the 24 hours following surgery. Of the total number of patients enrolled in the study, 104 were randomly assigned to the group receiving cryopreserved platelets. A total of 202 cryopreserved platelet units were administered.

Of the enrolled patients in CLIP-II, almost one-third (30.2%) underwent urgent or emergency surgery. The most common procedure was aortic valve replacement (51%), followed by aortic root surgery (38%) and coronary artery bypass grafting (35%). In many cases, the surgery included a combination.

Trial Results
The primary outcome for the study was bleeding in the first 24 hours after admission to the Intensive Care Unit. Such bleeding in the group that received cryopreserved platelets did not exceed the non-inferiority threshold of 605 mL vs. 535 mL (ratio = 1.13; 95% confidence interval = 0.96-1.34; p = 0.13). No difference in any prespecified safety outcome was observed.

However, Reade noted that intraoperative and total perioperative blood loss were higher for the group that received cryopreserved platelets. The higher blood loss was also associated with a need for transfusion of red cells, plasma and cryoprecipitate. He also reported that secondary endpoints of CLIP-II suggest that cryopreserved platelets might be less effective in reducing bleeding in settings other than cardiac surgery.

In closing, Reade observed that even though cryopreserved platelets proved to be 30% less effective in restoring hemostatic balance, their use can be of benefit in military, rural and other settings in which liquid platelets are not available. He mentioned a New Zealand study and one in the United States that, when completed, may shed additional light on the possibilities for use.