1. Publication
- Title: Cryopreserved vs Liquid-Stored Platelets for the Treatment of Surgical Bleeding: The CLIP-II Randomized Noninferiority Clinical Trial
- Acronym: CLIP-II
- Year & Journal: JAMA, epublished December 8, 2025 (print: 2026;335(7):600-608)
- Citation: Reade MC, Marks DC, Howe BD, et al; CLIP-II Investigators. JAMA. 2026;335(7):600-608. doi:10.1001/jama.2025.23355
2. Context & Rationale
Background: Liquid-stored platelets (22°C, 5-7 day shelf-life) cause periodic shortages and wastage. DMSO-cryopreserved platelets (-80°C, up to 2-year shelf-life) could improve availability in remote/military/regional settings if proven noninferior.
Research Question/Hypothesis: In cardiac surgery patients at high bleeding risk, is cryopreserved platelet transfusion noninferior to liquid-stored platelets for reducing postoperative chest-drain bleeding within 24h of ICU admission?
3. Design & Methods
- Study Type: Multicenter, randomized, double-blind, parallel-group noninferiority trial
- Setting & Centers: 11 Australian tertiary hospitals; Aug 2021–Apr 2024
- Population: Cardiac surgery patients at high risk of platelet transfusion (ACSePT score); 879 screened, 388 randomized, 202 received study platelets
- Intervention: Cryopreserved platelets, up to 3 units (n=196)
- Comparator: Liquid-stored platelets (n=192)
- Statistical Power & Follow-Up: Noninferiority margin: <20% greater bleeding. Primary: postsurgical chest-drain bleeding, first 24h post-ICU-admission.
4. Key Results
Outcome | Cryopreserved | Liquid-Stored | Effect Size | 95% CI | Notes |
Chest-drain bleeding, 24h (primary) | 605 mL | 535 mL | Ratio 1.13 | 0.96–1.34 | Did not meet noninferiority |
Intraoperative/total perioperative blood loss | Higher | — | — | — | Additional endpoints indicated diminished hemostatic effectiveness |
Cost-effectiveness (companion study) | More costly, less effective | — | — | — | Per JAMA Netw Open companion analysis |
5. Internal Validity Assessment
Double-blind, adequately conducted noninferiority trial across 11 centers; consistent secondary endpoints support the primary noninferiority failure as a genuine, credible finding rather than chance. Overall: Strong.
6. External Validity Assessment
Australian high-bleeding-risk cardiac surgery population — directly relevant to the intended use case (regional/remote/military blood supply).
7. Strengths & Limitations
Strengths: Double-blind noninferiority design; companion cost-effectiveness analysis; definitive answer to a genuine logistics question.
Limitations: Substantial pre-randomization attrition (879→388→202 receiving platelets) may affect generalizability of the treated subgroup.
8. Interpretation & Practice Impact
Does not support routine substitution of cryopreserved for liquid-stored platelets in elective high-risk cardiac surgery — despite the logistics appeal (2-year vs 5-7 day shelf-life), cryopreserved platelets showed diminished hemostatic effectiveness and were more costly and less effective per the companion cost-analysis.
9. Controversies & Subsequent Evidence
Accompanying JAMA editorial ("An Oasis in the Platelet Desert?") frames the practical tension between logistics benefit and hemostatic performance. Investigators note this clarifies (rather than eliminates) cryopreserved platelets' role — likely still valuable in true platelet-desert settings (military, remote) where liquid platelets are simply unavailable, despite inferior performance vs same-day liquid product.
10. Summary & Executive Takeaway
Summary: CLIP-II randomized 388 high-bleeding-risk cardiac surgery patients across 11 Australian hospitals to cryopreserved or liquid-stored platelets. Cryopreserved platelets did not meet the noninferiority threshold for 24h chest-drain bleeding (ratio 1.13, 95% CI 0.96-1.34), with diminished hemostatic effectiveness on additional endpoints and higher cost.
Overall Takeaway: Cryopreserved platelets are hemostatically inferior to liquid-stored platelets and more costly — not a substitute where liquid platelets are readily available, though they likely retain a role specifically where liquid platelets are logistically unavailable (remote, military, disaster settings).
11. Bibliography
- Orman Z, Reade MC, Marks DC, et al. Cost-Effectiveness of Cryopreserved vs Liquid-Stored Platelets. JAMA Netw Open. 2025;8(12):e2554363.
- Neal MD, Spinella PC, Kornblith LZ. An Oasis in the Platelet Desert? [editorial]. JAMA. 2025.