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Platelet Rich Plasma (PRP) - Why Platelet Dosing Matters

Here is something you’re definitely going to want to ask your healthcare provider before you get a platelet rich plasma treatment. What is my final PRP platelet concentration and how many platelets will I have in my PRP? This study looked at how many platelets are necessary to get the BEST outcomes when treating knee arthritis. Let’s look at what they found and I’ll explain why platelet counts are critically important to PRP success.

Over the last few years, studies have consistently shown that platelet rich plasma injections are excellent at reducing pain and symptoms related to knee arthritis. Just a few weeks ago, another systematic review and meta-analysis looking at the use of PRP for knee arthritis concluded that “PRP improves pain and function in patients with knee osteoarthritis for up to 12 months and is superior to hyaluronic acid injections.”

But occasionally, one study will publish conflicting results. One of these studies was the RESTORE trial published in JAMA in November of 2021. And I want to use the RESTORE trial as a perfect example on why the number of platelets in your PRP is critical to achieving the best outcomes.

Let’s first look at what they concluded. After one year of follow up, the RESTORE trial found that PRP injections did NOT result in significant difference in symptoms for knee osteoarthritis when compared to saline placebo injections at 12 months. So first of all, the RESTORE trial was a very well designed and very well conducted study. The big problem with the study is that it had a fatal flaw from the very beginning. They used a PRP preparation kit that obtained about 1 billion platelets per injection. And we’re going to soon learn why their low PRP platelet count resulted in inferior outcomes.

But let me first give you another example on how this would matter. Let’s say I have someone with high blood pressure and I give them a 10 milligram dose of a blood pressure medication. Now let’s say the actual therapeutic dose is 100 milligrams. So when my patient comes back and tells me hey this medication didn’t work. Is it because the medication truly is not effective for high blood pressure or is it because we just didn’t prescribe a high enough dose?

This is exactly what happened in the RESTORE trial. They used a PRP preparation kit that gave them a small dose of platelets, which came out to around 1 billion platelets per injection. Now let’s look at this recent study that argued you need 10 billion platelets in your PRP to maximize effects. This would be ten TIMES the amount of platelets compared to the RESTORE trial.

So this other study randomized 150 patients to either get one PRP injection or one hyaluronic acid injection and then measured outcomes at 1 month, 3 months, 6 months, and 12 months. Their PRP preparation included taking 50 cc’s of blood and concentrating it down to a total volume of 8 cc’s of PRP. This gave a total count of around 10 billion platelets. No activating agent was used. For their control group, subjects got hyaluronic acid, specifically Monovisc, which is a high molecular weight HA preparation that is commonly used in the United States.

The researchers found that at 1 month, both the PRP and the HA group had significant improvements to functional and pain scores. However after one month, the initial improvements from the HA group steadily declined and were back to baseline by 6 months. In contrast the PRP group continued to have significantly better scores all the way out to 1 year of follow up.

The authors go on to conclude that “application of PRP with absolute counts of 10 billion platelets alleviates symptoms compared to control in knee osteoarthritis.”

Ok so here are my thoughts on this study. There is a big trend in PRP research recognizing that platelet count is incredibly important to patient outcomes. Every new clinical trial publishing data on platelet rich plasma is expected to report their PRP composition which includes platelet numbers and concentration. And this is critically important as the RESTORE trial has shown us. We need to make sure that if a study concludes that PRP has no benefits, that it’s because PRP really doesn’t work, NOT because they used a subtherapeutic dose of platelets.

So the question now is, how many platelets do you actually need? The study we just reviewed suggested we should aim for 10 billion platelets in one PRP injection. However, another recent study comparing PRP to hyaluronic acid for hip arthritis found benefits with 7 billion platelets. This next study compared a single PRP injection to a single treatment of adipose derived mesenchymal stem cells for knee arthritis. They had 21 billion platelets in their PRP and they found that PRP was equivalent to stem cells. This study compared a single PRP injection to a single treatment of bone marrow derived mesenchymal stem cells. They had 9 billion platelets in their PRP and they too found that PRP was equivalent to stem cells.

What’s really fascinating is that when we use more platelets, not only are we getting better outcomes and even similar outcomes to stem cell injections, we’re learning that one PRP injection can provide improvements to symptoms for up to 1 year.

So why do previous studies suggest you need 2 or even 3 injections? Here’s a perfect example. This study found that giving three PRP injections resulted in clinically significant functional improvements for up to 1 year. The study found platelet rich plasma injections had better improvements to symptoms when compared to hyaluronic acid as well as to placebo saline injections. But they used a kit that isolated around 1 to 2 billion platelets per PRP injection. So three injections would give us a total of around 3 to 6 billion platelets over the course of treatment. This would still be less than newer PRP preparations that allow us to harvest 7 to 10 billion platelets in a single treatment. But why would we want to do multiple shots if just drawing more blood and concentrating it in a newer system produces better results?

I really hope you’re starting to see why the emphasis on platelet count is so important. Technology is allowing us to increase the number of platelets and growth factors retained in our PRP. It really seems like the more platelets and growth factors we get, the better the outcomes. And we would only need to do the injection once a year.

Now the other thing that I want to point out is that our study found that at one year of follow-up, 38% of patients in the PRP group required retreatment as symptoms had increased closer back to baseline. This is still much less than the 53% in their control group. Again these results are consistent with what previous trials have shown and this is why many healthcare providers including myself recommend repeat PRP treatment at around 1 year.

So for those of you looking at getting PRP injections, make sure you ask your healthcare provider some very important questions. How many platelets will be in your PRP? What kit are they using? It really seems like you want to target a minimum of 5 to 10 billion platelets. Anything lower than that, you may need more than one injection to get the same outcomes.

The bigger red flag is if your healthcare provider is unable to answer these questions, then you may want to find someone more experienced in the field of orthobiologics and cellular therapy. PRP treatments are still relatively new and you want to make sure you don’t make the same mistake the RESTORE trial made.


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