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Why PRP Injection Platelet Dosing ACTUALLY Matters



Platelet rich plasma injections are one of the best treatments for knee osteoarthritis. But what most people don’t realize is that not all PRP is the same. There is a big difference between low dose PRP and high dose PRP and now we have data from a randomized controlled trial to tell us just how important this distinction is. 


Just like with any other medication, platelet rich plasma has a dose response curve. This means if we don’t administer enough platelets, you won’t see meaningful improvements. We learned this lesson from the RESTORE trial which made headlines in the Journal of the American Medical Association.


The study compared PRP injections to placebo for the treatment of knee osteoarthritis. They concluded that platelet rich plasma injections did NOT result in significant differences in symptoms at 12 months and that their findings do NOT support the use of PRP for knee osteoarthritis.


So even though the trial was well designed and well executed, it had a fatal flaw. The study used commercial kits called RegenLab BCT kits which, according to the manufacturer, involves a 10 cc blood draw and concentrates platelets to 1.6 times baseline levels for around 1 to 2 billion platelets. For comparison a high dose PRP kit would start with a 60 cc blood draw which is 6 times the amount of blood and platelets that is then processed and concentrated for treatment.


Now this next part is really important. The true definition of platelet RICH plasma is a platelet concentration of at LEAST 3 to 4 times higher than the baseline levels in whole blood. Therefore, the product used in the RESTORE trial, which was only a 1.6 times concentration, did not even qualify as platelet RICH plasma. And because they severely underdosed their treatment, this explains why the study found PRP injections were no more effective than placebo.


Now let’s look at what happens when we use a higher dose of platelets. This recent clinical trial directly compared high dose PRP to low dose PRP.


The study was a randomized controlled trial comparing high dose PRP to low dose PRP for the treatment of knee osteoarthritis. 50 to 60 cc of blood was drawn and prepared using a double spin protocol. The final product was a total of 16 ml of PRP which was then divided into two samples of 8 ml PRP per knee. Group A got 4 ml per knee which came out to around 2.82 billion platelets per knee, while Group B got 8 ml per knee which came out to around 5.65 billion platelets per knee. 


The results showed that group B had better improvements in pain and function at 3 months and at 6 months when compared to group A. The findings of this study are so important because it is the first study that actually proves higher dose PRP is more effective than lower dose PRP when it comes to arthritis.


This claim is further supported by a recent systematic review and meta-analysis that analyzed nearly 30 clinical trials studying the use of PRP for knee osteoarthritis. They found that studies that found positive benefits had a mean platelet dose of around 5.5 billion platelets whereas studies that found no benefit had a mean platelet dose of around 2 billion platelets. The authors conclude that higher platelet dose likely results in improved clinical outcomes.


We actually see the same effects when it comes to soft tissue injections. Platelet dosing is critical to ensure optimal outcomes when treating partial tendon tears as well as tendinopathies. This review found that studies using higher platelet dose resulted in significantly better outcomes than the studies that used low dose PRP. 


Take a look at this graphic. Each number is a clinical trial examining the effectiveness of PRP. The X-axis is the dose of platelets used in the trial. The vertical line in the middle is the cutoff at 3 billion platelets. All studies that found PRP was not effective used platelet doses of less than 3 billion platelets. The studies that found PRP resulted in significant outcomes all used doses of greater than 3 billion platelets.


The reality is that platelet rich plasma is quickly becoming the best injection we have for many orthopedic conditions. When it comes to knee osteoarthritis, systematic reviews and meta-analyses continue to find that PRP injections outperform other treatments such as corticosteroids, hyaluronic acid, and placebo. 


Even professional organizations are taking note. For example, the European Society of Sports Traumatology, Knee Surgery and Arthroscopy put out recent a consensus statement that said “according to the results from this consensus group, given the large body of existing literature and expert opinions, PRP was regarded as a valid treatment option for knee OA and as a possible first-line injectable treatment option for nonoperative management of knee OA, mainly for KL grades 1-3.” 


The same is true for American medical societies. Both the American Academy of Orthopedic Surgeons and the American Medical Society for Sports Medicine have acknowledged the effectiveness of PRP. They’ve released summaries and consensus statements highlighting PRP’s significant benefits in reducing pain and enhancing joint function in knee osteoarthritis. 


But I want to reiterate that not all PRP is the same and dosing affects outcomes. The reason this matters to you is because most orthopedic surgeons and sports medicine physicians and clinicians who offer PRP do not understand this yet. The vast majority of providers use similar low dose commercial PRP kits for processing because of cost. And the main reason why they do this is because they assume all PRP kits are the same and so why wouldn’t they go for the cheapest ones to minimize pricing. 


So whenever I see a patient who has tried PRP in the past but did not notice improvement, the first thing I ask is how much blood was drawn. Almost always, only a small volume of blood was used, confirming my suspicion that they received a low dose plasma injection rather than true platelet RICH plasma.


At the time of this video recording, I currently recommend using around 10 billion platelets to treat osteoarthritis of large joints such as knees, hips, and shoulders. Smaller targets like tennis elbow and plantar fasciitis seem to do extremely well with around 5 billion platelets.


The key takeaway from these studies are that platelet dosing really matters when it comes to PRP. It’s one of the most important factors to consider when getting platelet rich plasma treatments.

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