3 PRP Injection Mistakes That Ruin Your Results

By Dr. Jeffrey Peng, MD

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I've identified three critical mistakes people often make with PRP injections, and these can directly translate into disappointing outcomes. Fortunately, all of these mistakes are entirely preventable. I'm going to share what I believe are the most common PRP problems and how you can avoid them. The goal is to help you achieve the best possible outcomes from your platelet-rich plasma treatments.

I'm a sports medicine physician currently practicing in the San Francisco Bay Area, and I've helped thousands of patients navigate orthobiologic treatments like PRP injections. Clinical trials continue to show that platelet-rich plasma consistently outperforms many treatments for osteoarthritis, tendon tears, and tendinopathies. But it's also important to understand that not all PRP is the same. Many variables affect success rates and can lead to poor outcomes.

Why does low-dose PRP fail?

Mistake number one is platelet dosing. Like 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 and the PEAK trial.

The RESTORE trial concluded that:

The PEAK trial concluded that:

Now, both of these were really well-designed and well-executed studies, but they both had an important limitation. Both used PRP injections that were considered low dose PRP. One study made their PRP using a 10 cc blood draw, which ballparks to around 1 to 2 billion platelets. The other study used a 15 to 20 cc blood draw, which ballparks to around 2 to 3 billion platelets.

Let's compare that with a 2022 study by Chu and colleagues that used a much higher dose of PRP. That study started with a 50 cc blood draw and, after processing, ended up with a platelet concentration 4.3 times that of whole blood. Their platelet counts were around 4 to 5 billion platelets per injection. The results showed that PRP was superior to placebo for pain, function, and overall arthritis symptoms, and that 3 high-dose PRP injections significantly decreased inflammatory markers in the knee joint and slowed arthritis progression by up to 50% compared with placebo.

This matters because most orthopedic surgeons, sports medicine physicians, and clinicians who offer PRP still don't understand the nuances of platelet dosing. And I've seen a lot of orthopedists still use low-dose PRP. 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, the reason they didn't notice any changes is that they got a low dose PRP.

We actually have review articles now that highlight the importance of platelet dosing. For example, a 2024 review by Berrigan and colleagues writes that "dose-response relationship between platelet dose and PRP effectiveness for knee OA treatment, pinpointing an optimal threshold of greater than 10 billion platelets for favorable clinical outcomes."

We see similar effects with soft tissue injections. Platelet dosing is critical to ensure optimal outcomes when treating partial tendon tears and tendinopathies. A 2023 review by Everts and colleagues found that studies using higher platelet doses produced significantly better outcomes than studies using low-dose PRP.

How much blood should be drawn?

So, here's what you need to do to prevent a dosing error. Number 1: You MUST ask your provider how much blood they will draw for your PRP treatment. This will give you a good estimate of how many platelets will end up in your injection. The more blood that is drawn, the higher the dose of platelets you are getting.

I've found large joint injections such as knees and hips do far better with a 50 or 60 cc blood draw to get around 10 billion platelets. I'm even seeing benefits of doing 120 cc blood draws to get closer to 20-24 billion platelets with great results. Smaller targets like tendons or ligaments may require fewer platelets than large joints. With that said, I still think they need at least 5 billion platelets, which is at least a 30 cc blood draw.

Number 2: a larger initial blood draw does NOT guarantee that the centrifuge process will efficiently recover platelets. Some single-spin protocols might get less than 50% platelet recovery, which means you still aren't getting a high dose. Double-spin centrifuge protocols have significantly higher platelet recovery, which translates into a higher dose and better outcomes.

Lastly, number 3: once you've ensured you're getting high-dose PRP and the processing is ideally done with a double-spin centrifuge protocol, it's crucial to inject the entire sample into a single spot. I've encountered numerous cases where the sample was split into five syringes and dispersed around the intended site. Think about this. If the target needs 10 billion platelets, and you divide that into 5 syringes, you are now injecting 2 billion into each area. This means you are back to injecting a low-dose PRP, and this will result in suboptimal outcomes. You must deliver all 10 billion platelets directly to the target.

Why does imaging guidance matter?

Imaging guidance is essential for platelet-rich plasma injections. It doesn't matter how many years of experience your doctor has. Even the most skilled and seasoned orthopedic providers can miss their injections. And you certainly don't want to be the one that they miss.

Landmark-based accuracies often range in the low to mid 60s. Ultrasound guidance almost always ensures accuracy. The last thing you want to do is undergo a medical procedure only for your health care provider to do a landmark-based injection and then miss the target.

Moreover, for PRP injections for soft tissue conditions like partial tendon tears and tendinopathy, accurate platelet placement is essential for success. The most dependable way to ensure PRP reaches the right spot is with imaging guidance. Don't let anyone convince you that they can simply 'feel' the problem area and accurately inject the PRP. They don't have X-ray vision, and they can't 'feel' where a tear is. That's not how it works.

Clinical trials show that imaging guidance leads to better outcomes. Researchers from de Castro and colleagues (2023) performed ultrasound-guided tendon debridement followed by either PRP injections or a saline placebo. Remarkably, 87% of the PRP-treated group experienced a reduction in tear size by the six-month mark, with 79% achieving complete healing. In contrast, only 32% of tears in the saline placebo group decreased in size, and just 21% reached full healing.

These results just aren't possible with the old-school method of using landmark-based injection techniques. To replicate these results, you must perform the procedure with imaging guidance. So here's what you need to do. Ask whether your PRP injection will be done with imaging guidance. If you get pushback, consider finding another provider who has the technical skills to ensure correct placement.

Should I stop NSAIDs before PRP?

The last mistake when it comes to PRP injections is taking NSAID medications. Common medications in the NSAID class of drugs include aspirin, ibuprofen, naproxen, diclofenac, and indomethacin. Platelets release growth factors that are crucial for the healing process. Because of their mechanism of action, NSAIDs inhibit platelet function, potentially reducing the effectiveness of the growth factors PRP therapy relies on to initiate tissue repair.

A 2019 study by Jayaram and colleagues found that daily use of low-dose aspirin reduced vascular endothelial growth factor, platelet-derived growth factor, and TGF beta-1 expression in platelet-rich plasma. This means that if you take NSAIDs before your PRP procedure, your platelets may not be able to initiate the growth-factor release cascade needed for a proper response.

In addition, while chronic inflammation can be harmful, acute inflammation is an essential part of the body's natural healing process. NSAIDs reduce inflammation, but in the context of PRP therapy, this may not always be beneficial. The initial inflammatory response after a PRP injection is a crucial step in healing, as it signals the body to begin repairing injured tissue. By dampening this response, NSAIDs could hinder the effectiveness of PRP therapy.

This is exactly what we see in a 2022 animal study by Sok and colleagues. Rats given NSAIDs after orthobiologic injections had significantly worse arthritis when compared to rats that got treatments without NSAIDs. Taking these medications after injections inhibits the release of growth factors, which results in worse outcomes.

Now there are some studies to suggest that selective NSAIDs such as meloxicam and celecoxib may not significantly impair the healing process, but the evidence is still inconclusive. In my opinion, if you are going to get PRP, you might as well try to come off all NSAIDs to minimize disruption to your PRP.

So here's what I recommend: stop taking NSAIDs at least 1 week prior to your PRP injection. Continue to hold them for at least 2 weeks after the treatment and ideally up to 6 weeks. The longer you can hold off taking NSAIDs after a biologic treatment, the better the outcomes.

Bottom Line

In summary, the three most common mistakes made with PRP injections are incorrect platelet dosing, not getting injections with imaging guidance, and not stopping NSAID medications. But many other factors can also negatively affect your platelets and impact results.

If you want help avoiding these mistakes, schedule a consultation at my Campbell clinic.

Related Reading

• PRP platelet count: how many platelets you need for an effective injection

• New study says PRP injections do not work -- why they are wrong

• Does PRP work for bone-on-bone knee arthritis?

• Do PRP injections hurt? What to expect for pain and recovery

References

1. Bennell KL, et al. Effect of intra-articular platelet-rich plasma vs placebo injection on pain and medial tibial cartilage volume in patients with knee osteoarthritis: the RESTORE randomized clinical trial. JAMA. 2021. PMID: 34812863. PubMed 34812863

2. Lewis E, et al. The effectiveness of leucocyte-poor platelet-rich plasma injections on symptomatic early osteoarthritis of the knee: the PEAK randomized controlled trial. Bone Joint J. 2022. PMID: 35638203. PubMed 35638203

3. Chu J, et al. Intra-articular injections of platelet-rich plasma decrease pain and improve functional outcomes than sham saline in patients with knee osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2022. PMID: 35124707. PubMed 35124707

4. Berrigan W, et al. The effect of platelet dose on outcomes after platelet rich plasma injections for musculoskeletal conditions: a systematic review and meta-analysis. Curr Rev Musculoskelet Med. 2024. PMID: 39331322. PubMed 39331322

5. Everts PA, et al. Angiogenesis and tissue repair depend on platelet dosing and bioformulation strategies following orthobiological platelet-rich plasma procedures: a narrative review. Biomedicines. 2023. PMID: 37509560. PubMed 37509560

6. Daniels EW, Cole D, Jacobs B, Phillips SF. Existing evidence on ultrasound-guided injections in sports medicine. Orthop J Sports Med. 2018. PMID: 29511701. PubMed 29511701

7. de Castro RLB, et al. Total healing of a partial rupture of the supraspinatus tendon using barbotage technique associated with platelet-rich plasma: a randomized, controlled, and double-blind clinical trial. Biomedicines. 2023. PMID: 37509489. PubMed 37509489

8. Jayaram P, et al. Effects of aspirin on growth factor release from freshly isolated leukocyte-rich platelet-rich plasma in healthy men. Am J Sports Med. 2019. PMID: 30888847. PubMed 30888847

9. Sok D, et al. NSAIDs reduce therapeutic efficacy of mesenchymal stromal cell therapy in a rodent model of posttraumatic osteoarthritis. Am J Sports Med. 2022. PMID: 35420503. PubMed 35420503

This content is for educational purposes only and does not substitute for the medical advice of a physician. Always consult your healthcare provider before beginning any new treatment program. The information presented reflects the opinion of Dr. Jeffrey Peng and does not represent the views of his employers or affiliated hospital systems.