Creating the Perfect PRP
Dr. J. Corey Orava
What is the optimal composition of Platelet Rich Plasma? I have been asked this question countless times and my answer is always the same. It depends. It depends on the injury. Is it acute or chronic? Is the wound clean or contaminated? Is the structure a joint or a tendon? It should be obvious to anyone with medical training that there is no single formulation of PRP that will work best for each condition. In the coming weeks I will review the scientific literature and summarize what is known about the various cellular components of PRP, namely: leukocytes, platelets and erythrocytes. Today we will address white blood cells.
Likely the most contentious topic in PRP today is leukocytes. Should I use leuko-depleted? Leuko-rich? When PRP started gaining traction around a decade ago leukocytes were considered synonymous with inflammation. ‘If you have white cells you have an increased risk for a joint flare’ was commonly heard amongst huddled clinicians. It soon became dogma that PRP should be leuko-depleted. In some circles, that dogma has persisted.
A quick search of PubMed for the term “platelet rich plasma” reveals over 11,000 hits. Rather than try to evaluate every condition for which PRP has been used, we will focus on tendon injuries and osteoarthritis. Even still, adding the terms “tendinopathy” or “osteoarthritis” to the search yielded over 500 and 700 hits, respectively. Amongst all these papers there are very few that actually compared leuko-RICH to leuko-POOR. Fortunately, systematic reviews and meta-analyses have been performed. These studies combine multiple clinical trials in one big study. Given sufficient data these studies can investigate variables, such as leukocytes, to determine if one type of PRP is more likely to be associated with positive outcomes.
Beginning with tendon injuries, Fitzpatrick et al, academics from Australia with no declared conflicts, reviewed 18 randomized controlled trials, totaling over 1,000 patients. Their conclusion:
“Our systematic review and network meta-analysis found strong evidence that LR-PRP improves outcomes in tendinopathy”
That is, with tendon injuries leuko-RICH PRP was more likely to be associated with a positive outcome. Dogma confirmed? Not so fast. We need to address PRP and osteoarthritis. In this case we have four papers to evaluate. Some of their conclusions:
“LP-PRP was the highest ranked treatment for both measures of clinical efficacy” – Riboh et al
“it appears … avoidance of leukocytes should be preferred.” – Milants et al
In the meta-analysis by Dai et al, they noted that overall PRP performs better than hyaluronic acid for osteoarthritis. However, when then investigated subgroups they observed that leuko-RICH PRP did not provide the same pain relief.
Further, a recent publication by Wakayama et al directly compared a leuko-RICH PRP with a leuko-POOR PRP for knee osteoarthritis. They found that adverse events were more common and lasted longer when leuko-RICH PRP was used.
In summary, not all PRP is created equal. The current best evidence suggests that when used for tendon injuries, PRP should contain leukocytes. In contrast, when used for osteoarthritis, PRP should be leuko-POOR.
Dai, W-L et al. Efficacy of Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis: A Meta-analysis of Randomized Controlled Trials. Arthroscopy 2017, Vol 33, No 3 (March): pp 659-670.
Fitzpatrick, J et al. The Effectiveness of Platelet-Rich Plasma in the Treatment of Tendinopathy A Meta-analysis of Randomized Controlled Clinical Trials. Am J Sports Med 2016, Vol. 45, No. 1.
Milants, C et al. Responders to Platelet-Rich Plasma in Osteoarthritis: A Technical Analysis. BioMed Research International 2017, Article ID 7538604.
Riboh, J et al. Effect of Leukocyte Concentration on the Efficacy of Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis. Am J Sports Med 2016 Mar;44(3):792-800.
Wakayama, T et al. Quality comparison between two different types of platelet-rich plasma for knee osteoarthritis. Regen Med Res 2020, 8, 3.
Click here to visit our PRP page for basic information on platelet rich plasma (PRP).
About the author: Dr. J. Corey Orava is the Chief Science Officer for both Enso Doctors and Enso Discoveries. In his capacity as CSO he oversees all scientific affairs. This includes designing, developing, and validating new medical devices. Dr. Orava is a sought-after lecturer for regenerative medicine, both nationally and internationally. He has lectured on both human and veterinary topics in Beijing, Bangkok and most recently the 47th Annual Conference of Orthopedic Surgeons Society in Tirupati, India.
Dr. Orava received his Doctor of Veterinary Medicine degree with honors from the Ontario Veterinary College. He then furthered his education with an intensive year-long internship at the Atlantic Veterinary College at the University of Prince Edward Island.
First introduced to regenerative medicine in the early 2000s, Dr. Orava was so impressed and inspired by the transformative therapy, he left his position as an equine veterinarian at a progressive sports horse practice to pursue full-time work focused on regenerative medicine.
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