The initial FDA approval for pathogen-reduced (PR) platelets was supported by data from the SPRINT trial1,2 showing PR platelets to be noninferior to control platelets with respect to the incidence of bleeding after transfusion to thrombocytopenic patients; only about 16% of whom had clinically significant bleeding on study entry. Are PR platelets as effective as non-PR platelets in actively bleeding patients?
A recent article by Fontaine et al. addressed this question in a single-center trial.3 The study population consisted of adult cardiac-surgery patients after discontinuation of cardiopulmonary bypass who had either clinically significant bleeding or clinical bleeding and a ROTEM EXTEM amplitude at 10 min less than 40 mm. Each patient was given a PR unit of platelets in PAS or a non-PR unit in PAS that was negative by bacterial culture, depending on product availability. The primary outcome was the maximum amplitude (MA), a thromboelastography (TEG) metric directly related to the platelet contribution to clot. The change in maximum amplitude (ΔMA) was defined as the MA 60 minutes after transfusion less the MA before transfusion.
As a trade-off for the increased bacterial safety of PR platelets, they were considered noninferior to non-PR platelets if they produced a ΔMA at least half of that produced by non-PR platelets. To achieve the desired power to detect noninferiority, each arm of the study needed 51 patients. Of the 150 patients who consented to be study subjects, 60 were excluded for various reasons, mostly for not needing platelets. Forty-two of the remaining patients received non-PR platelets, and 48 received PR platelets. The 90% confidence interval for the mean ΔMA ratio was (0.29, 0.89). Because a statistical test could not reject the margin of 0.5, PR platelets did not meet the criterion of non-inferiority to non-PR platelets. However, if the study had been designed as an equivalence trial in which the difference between the ΔMA for PR platelets and that for non-PR platelets was compared to zero, the associated test’s p-value would have been 0.052, and the ΔMA values for the two platelet types would have not been significantly different.
After each patient received an initial platelet unit of a specific type, each subsequent unit could be of either type, depending on availability (Jun 29, 2025 e-mail from Magali Fontaine to Barry Siegfried; unreferenced, see “Note”). Given that over half of the patients in each arm received 1-5 additional platelet units, this practice would minimize differences between the arms and may explain why the arms had no difference in chest tube drainage; the units of platelets, RBCs, FFP, and cryoprecipitate transfused; and prothrombin complex concentrate and Factor VIIa used during the 24 hours after surgery. Why fibrinogen concentrate was given to more patients in the PR arm (52%) than in the non-PR arm (12%) could not be explained.
This study suggests that PR platelet units may contribute less to clot strength but has limitations. The desired statistical power was not achieved. The extent to which the lower platelet dose and lower 1-hour CCI in PR products2 may have accounted for their reduced ΔMA was not determined. The mean pre-transfusion MAs in both arms were within the normal reference range4 and above platelet transfusion triggers used successfully in other cardiac surgery studies.5,6 If the starting MAs had been lower, the effect of PR platelets on ΔMA, chest tube drainage, and additional blood product use might have been different.
In summary, PR platelets demonstrated a trend towards an inferior contribution to clot strength by TEG when compared to non-PR platelets. Future studies may reveal whether this trend has a clinically significant impact on hemostatic function, especially for patients with a higher degree of pre-transfusion coagulopathy. Controlling for the known effects of PR on platelet dose and recovery may or may not reveal an intrinsic defect in treated platelets transfused into bleeding patients.
References
1. U.S. Food & Drug Administration [Internet]. Silver Spring (MD): U.S. Food and Drug Administration; [cited 2025 Jun 28]. Summary of safety and effectiveness data (SSED); 2014 Dec 18. In: Internet Archive Wayback Machine [Internet]. San Francisco (CA): Internet Archive; [cited 2025 Jun 28]. 43 p. Available from: https://wayback.archive-it.org/7993/20190208123649/https://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/PremarketApprovalsPMAs/UCM431243.pdf
2. McCullough J, Vesole DH, Benjamin RJ, Slichter SJ, Pineda A, Snyder E, Stadtmauer EA, Lopez-Plaza I, Coutre S, Strauss RG, Goodnough LT, Fridey JL, Raife T, Cable R, Murphy S, Howard F 4th, Davis K, Lin JS, Metzel P, Corash L, Koutsoukos A, Lin L, Buchholz DH, Conlan MG. Therapeutic efficacy and safety of platelets treated with a photochemical process for pathogen inactivation: the SPRINT Trial. Blood. 2004;104:1534-41.
3. Fontaine MJ, Lasola JJM, Martinez-Hernandez A, Marshall JN, Bentzen S, Zhan M, Lokhandwala PM, Tanaka K, Villa CH, Jones A, Atreya CD, Henderson RA. A prospective non-inferiority trial of pathogen reduced platelets compared to non-pathogen reduced platelets for correction of viscoelastic platelet function testing in cardiac surgery. Transfusion. 2025 May 15. Epub ahead of print.
4. Walsh M, Thomas SG, Howard JC, Evans E, Guyer K, Medvecz A, Swearingen A, Navari RM, Ploplis V, Castellino FJ. Blood component therapy in trauma guided with the utilization of the perfusionist and thromboelastography. J Extra Corpor Technol. 2011 Sep;43(3):162-7.
5. Royston D, von Kier S. Reduced haemostatic factor transfusion using heparinase-modified thrombelastography during cardiopulmonary bypass. Br J Anaesth. 2001 Apr;86(4):575-8.
6. Redfern RE, Fleming K, March RL, Bobulski N, Kuehne M, Chen JT, Moront M. Thrombelastography-Directed Transfusion in Cardiac Surgery: Impact on Postoperative Outcomes. Ann Thorac Surg. 2019 May;107(5):1313-1318.
Note
By e-mail to Dr Barry Siegfried on Jun 29, 2025, Dr Magali Fontaine gave permission for this information to be included in this article.
