A sound theoretical mechanism and clinical indication are not enough—the case of Platelet Rich Plasma for Achilles tendon ruptures

A global industry has grown around using platelet rich plasma (PRP) in sports medicine. Its appeal has been heightened by use in high profile athletes. PRP has evolved over millennia. As nature’s most refined healing elixir of minute vessels packed with bioactive proteins, it stood every chance of being that new accelerant of tissue healing.

To produce PRP, the patient’s own blood is processed, usually in a specialised centrifuge, to produce a solution containing a supraphysiological concentration of platelets. But where does it lie in the spectrum between another fashionable application and a proven novel regenerative therapy? We set out to sift the evidence from the enthusiasm with an open mind, and to place some robust research quality markers that would allow proper critique.   

Our 2016 paper in The BMJ discussed the uncertainties in this area, and looked at how effective platelet rich plasma injections are in treating musculoskeletal soft tissue injuries. At the time there had been 29 randomised controlled trials, but it was difficult to draw clear conclusions about efficacy, because of PRP use in heterogeneous musculoskeletal conditions, underpowered studies, and poor reporting. [1]

Furthermore, few trials included an analysis of PRP content or quality, yet PRP had been adopted widely in clinical practice. Many commercially available PRP preparation devices had US Food and Drug Administration approval based on device performance and safety, but not clinical efficacy. [2] However, animal and cellular research was providing some encouraging evidence in support of a theoretical mechanism and potential effect. [3] 

It was because of the latter that we embarked upon the PATH-2 trial to investigate the efficacy of PRP. We identified acute Achilles tendon rupture as a suitable human injury to study, as it is common and patients often experience a frustrating recovery, due to slow tissue healing and recovery of muscle function. The case for robust evaluation was clear, however the complexity and cost of a randomised controlled trial were significant. We first conducted a pilot with embedded mechanistic studies to address the limitations of previous trials, then recruited to the largest trial of PRP to date in 19 UK hospitals. To standardise PRP, we provided the same specialist centrifuge to each hospital, standard operating procedures and training in blood sample handling, and tested all blood and PRP samples at a central laboratory. Recruiting participants in busy trauma clinics, and handling the masking of the PRP or dry needle injection were some of the challenges. For our findings to be unequivocal the primary outcome needed to be an instrumented muscle performance test by a blinded assessor; that ensured objective alongside patient-reported outcomes. 

The results of the PATH-2 trial are now published in The BMJ, and show that when subjected to robust evaluation, there is no evidence of patient benefit from injecting high quality PRP for acute Achilles tendon ruptures.

It took years of development, trialling, and evaluation, to deliver this negative finding. Some may think that this was a misplaced effort and resources. But safety and efficacy are paramount as no intervention is without risk or cost, even if autologous. This may not be the end of the PRP story. We assumed nature’s recipe of bioactive proteins released from activated platelets was the ideal, but perhaps some ingredients have more potency than others. There is a clear sense, however, that the many other current musculoskeletal PRP applications now need to be subjected to similar evaluation. There is also a wider message about adopting innovations into practice and the balance with robust clinical trial evaluation. Enthusiasm for using promising technologies and a strong theoretical justification from pre-clinical research are insufficient. This is especially important where new interventions are not subjected to the same regulations as new medicines.

David J Keene, NIHR Postdoctoral Research Fellow, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK. @davidkeenePT

Keith Willett, Professor of Orthopaedic Trauma Surgery, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK. 

Competing interests: See research paper.


  1. Keene DJ, Alsousou J, Willett K. How effective are platelet rich plasma injections in treating musculoskeletal soft tissue injuries? BMJ 2016;352:i517. doi: 10.1136/bmj.i517 
  2. Harm SK, Fung MK. Platelet-rich plasma injections: out of control and on the loose? Transfusion 2015;55(7):1596-8. doi: 10.1111/trf.13160 
  3. Alsousou J, Ali A, Willett K, et al. The role of platelet-rich plasma in tissue regeneration. Platelets 2013;24(3):173-82. doi: 10.3109/09537104.2012.684730