Characteristics of L-PRP preparations for treating Achilles tendon rupture within the PATH-2 study

Abstract

Platelet-rich plasma (PRP) is an autologous preparation that has been claimed to improve healing and mechanobiological properties of tendons both in vitro and in vivo. In this sub-study from the PATH-2 (PRP in Achilles Tendon Healing-2) trial, we report the cellular and growth factor content and quality of the Leukocyte-rich PRP (L-PRP) (N = 103) prepared using a standardized commercial preparation method across 19 different UK centers. Baseline whole blood cell counts (red cells, leukocyte and platelets) demonstrated that the two groups were well-matched. L-PRP analysis gave a mean platelet count of 852.6 x 10⁹/L (SD 438.96), a mean leukocyte cell count of 15.13 x 10⁹/L (SD 10.28) and a mean red blood cell count of 0.91 x 10¹²/L (SD 1.49). The activation status of the L-PRP gave either low or high expression levels of the degranulation marker CD62p before and after ex-vivo platelet activation respectively. TGF-β, VEGF, PDGF, IGF and FGFb mean concentrations were 131.92 ng/ml, 0.98 ng/ml, 55.34 ng/ml, 78.2 ng/ml and 111.0 pg/ml respectively with expected correlations with both platelet and leukocyte counts. While PATH-2 results demonstrated that there was no evidence L-PRP is effective for improving clinical outcomes at 24 weeks after Achilles tendon rupture, our findings support that the majority of L-PRP properties were within the method specification and performance.

Keywords:

• platelet-rich plasma
• Achilles
• tendon
• rupture

Acknowledgements

The PATH-2 trial was funded by the Efficacy and Mechanism Evaluation program, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership (reference 12/206/30). The trial was supported by the NIHR Biomedical Research Centre, Oxford, and the NIHR Fellowship program (DJK, PDF-2016-09-056). SEL receives funding from the NIHR Collaboration for Leadership in Applied Health Research and Care Oxford at Oxford Health NHS Foundation Trust. University of Birmingham staff were funded by the Scar Free Foundation (SFF) and the NIHR Surgical Reconstruction and Microbiology Research Centre (SRMRC). The views and opinions expressed herein are those of the authors and do not necessarily reflect those of the MRC, NHS, SFF, NIHR, or Department of Health and Social Care. The sponsor (University of Oxford) and funders monitored the study but were not involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclosures

We have no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; SEL reports personal fees from Pleuristem, Israel, for consulting on the design of trials of stem cell interventions in hip fracture management and KW declares design royalties from Zimmer Biomet (Warsaw, IN, USA), for intramedullary bone fixation implants, outside the submitted work; KW held the role of medical director for acute care, NHS England, during the conduct of this study.

Author Contributions

JA, DJK, PHa, PHu, SJD, SEL, and KW contributed to the study concept and design. PHa. MD, AW, AD, RD and JD all contributed to the laboratory analysis of PRP and blood samples. All the authors contributed to the acquisition, analysis, and interpretation of data. PHa, JA, DJK and KW drafted the manuscript. All the authors critically revised the manuscript for important intellectual content. HMO’C, MMS, SJD, SEL, JA and KW conducted the statistical analysis. DJK, JA, PHa, PHu, SJD, SEL, and KW obtained funding. SW, SRP, and JYT provided administrative and technical support. SEL and KW supervised the study. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. DJK and KW act as guarantors and take responsibility for the integrity of the data and the accuracy of the data analysis.

Additional information

Funding

This work was supported by the Efficacy and Mechanism Evaluation Programme [12/206/30].