Why Two PRP Injections Called the Same Thing Behave So Differently: Platelet Dose, Leukocytes and Preparation Method

Same Three Letters, Very Different Results: What Actually Varies Between PRP Preparations

I hear this one often in clinic: "I had PRP somewhere else and it did nothing."

My first question back is usually this. Do you know what was in the syringe that day?

Almost nobody does, and that is not the patient's fault. PRP (Platelet-Rich Plasma, a concentrate made by spinning your own blood and drawing off the platelet-rich layer) is not a bottle with a fixed specification. It is made on the spot from your blood. How much blood is drawn, how it is spun, which layer is taken, how much volume ends up in the syringe: every one of those steps changes the product. So "I have had PRP" carries less information than people assume.

This is not a new problem in the literature either. When DeLong and colleagues proposed the PAW classification in 2012, built on the platelet count itself, the way activation happens, and the presence or absence of white cells, they put it plainly: preparation protocols vary widely between authors and are often not well documented in published work, which makes results hard to compare and hard to reproduce. If studies cannot be lined up against each other, it is no surprise that the same name means different things in different clinics.

1. "Concentrated five times" is the phrase most easily misread

What most people are told is a multiple. Five times. Eight times.

A multiple is relative to your own baseline platelet count. Two people both given a five-fold concentrate do not receive the same amount if their baselines differ, and the body responds to the amount, not the ratio.

So the question is not the multiple. It is the dose: how much blood was drawn, what final volume went in, and roughly how many platelets were in it.

When Magalon and colleagues proposed the DEPA classification in 2016, covering the dose of injected platelets, efficiency of production, purity and activation, they applied it retrospectively to twenty published PRP preparations. The dose of injected platelets ran from 0.21 billion to 5.43 billion, roughly a 25-fold spread. One name, a 25-fold range underneath it.

Key point: A concentration multiple is a ratio. The number of platelets that actually goes in is the dose. Two people given the same multiple can receive very different amounts.

2. Dose matters, but not identically at every site

So how much is enough?

Berrigan and colleagues published a systematic review and meta-analysis in 2024 looking at platelet dosage across musculoskeletal indications. In knee osteoarthritis they found a possible dose-response relationship and identified a threshold above 10 billion platelets as associated with more favourable clinical outcomes, with the pattern more pronounced for functional measures than for pain. The same paper is candid about the rest: for other conditions the evidence is unclear, a lower dose may be sufficient, and the literature does not yet give an answer.

That is why I do not apply one fixed recipe everywhere. The volume a knee joint space holds, the size of a rotator cuff lesion, the room around the median nerve inside the carpal tunnel: the amount and concentration each needs are simply not the same. Whether PRP is the right starting point for you, or whether something else should come first, is covered in who is and is not suitable for regenerative treatment. Response still varies with individual tissue condition and needs an in-person assessment.

3. Whether to keep leukocytes in is still an open question

During centrifugation white cells are either carried up with the platelets or left behind, which gives leukocyte-rich LR-PRP and leukocyte-poor LP-PRP (Leukocyte-Poor PRP, filtered with an extra step to remove white blood cells, producing a gentler inflammatory response).

You will often hear that joints must always have the leukocyte-poor version or inflammation gets worse. There is physiological reasoning behind that, but the evidence is less settled than the confidence suggests. Nie and colleagues pooled 21 randomised controlled trials in knee osteoarthritis in 2021 and ran an indirect comparison of LR against LP; they found no significant difference between the two, and concluded that larger, higher-quality trials are needed to separate them.

So the honest version is this. Leukocyte content is a choice that should be recorded and explained, not a question with a settled answer. If someone tells you it is settled, it is fair to ask what they are basing that on.

4. Red-cell carryover and production efficiency rarely come up

The same DEPA review measured two things nobody usually mentions.

The first is purity. Most preparations carry residual red blood cells. Of the twenty assessed, only three reached an A grade, meaning platelets made up over ninety per cent of the cellular content. Red cells left in the mix are not neutral; they add inflammatory stimulus of their own.

The second is efficiency. No device was able to recover more than ninety per cent of the platelets from the blood drawn. In other words the conversion rate between how much blood comes out of your arm and how good the product is varies considerably between systems, and that part tends not to appear in any promotional material.

5. What is actually moving underneath the same name

This table is not there so you can quiz your doctor. It is there so that when two courses of PRP give very different results, you know the difference usually sits in one of those six rows rather than in "your body just does not respond to PRP".

6. Preparation is half of it. The other half is where it lands

However carefully the composition is described, a needle that misses is the same as no injection at all.

Lesions in ligaments, tendon insertions and the tissue around nerves are often only a few millimetres across, with vessels and nerves right beside them. Injected blind, the fluid may settle in the fat layer or outside the joint capsule, and the finest preparation in the world will do nothing there. That is why we perform joint and soft-tissue injections under high-grade ultrasound guidance: see the lesion and the structures around it first, then decide the path the needle takes, and watch the spread while injecting to confirm it reached where it should. Work around nerves depends on that confirmation even more, because there is no margin for error there.

Seeing it is what makes it safe to treat. That holds for injection work exactly as it holds for minimal-incision surgery.

Key point: PRP outcomes are the product of two things multiplied: what goes in, and where it lands. If either one is uncertain, quality in the other cannot make up for it.

7. What I confirm with you at consultation

Imaging and physical examination first, to establish which layer the pain is coming from: the joint surface, a tendon insertion, or a nerve under compression. Different source, different order of treatment. For some people the right first step is dextrose prolotherapy; for others it is one of the other two joint injections, which this comparison of PRP, hyaluronic acid and steroid sets out in more detail.

Only then do we talk about how the PRP itself will be done: blood volume, final volume, leukocytes rich or poor, how many sessions, what interval. Those get written down, so that at the next visit there is something concrete to compare against and adjust. Treatment without a record cannot accumulate, and that matters more than any single concentration figure.

To find out which situation your knee, shoulder or wrist falls into, you are welcome to arrange an online consultation and individual assessment, or start with the regenerative medicine and pain treatment overview.

Common questions

How do I find out the platelet dose in my own PRP?

Ask directly. Blood volume, final volume, single or double spin: the clinic has all of those numbers. A clinic willing to walk you through the protocol is usually also willing to keep the record. If you cannot even get "how many cc drawn, how many cc injected", the discussion about concentration has no foundation under it.

Is a higher platelet concentration always better?

What the literature supports is a dose threshold in knee osteoarthritis, not an open-ended "more is better". Concentration also has to be read together with volume, since a high concentration in a very small volume can still add up to a low total dose. How it is configured depends on the site and on individual tissue response.

Does a joint injection have to be leukocyte-poor PRP?

Physiologically, the leukocyte-poor version produces a milder inflammatory stimulus inside the joint space, which is why it is a common choice. But the indirect comparison in the pooled analysis has not shown a significant difference between the two, so it is a choice that should come with a reason rather than a rule that must be followed.

Why does the same clinic prepare PRP differently for different sites?

Because the anatomy differs. A joint space accommodates a larger volume; the tissue around a nerve and a tendon insertion do not. Deep joints need imaging guidance to find the correct plane at all. Adjusting the method to the site is normal practice, not inconsistency.

How soon will I know whether it worked?

Repair happens in stages, and tissue needs time to complete the response and remodel, so what we look at is the trend between visits rather than how the joint feels on the day. Comparing concrete situations at review, range of movement, night pain, stairs, tells you more than asking yourself whether it hurts less.

References

1. DeLong JM, Russell RP, Mazzocca AD. Platelet-rich plasma: the PAW classification system. Arthroscopy. 2012;28(7):998-1009. PMID: 22738751. DOI: 10.1016/j.arthro.2012.04.148
2. Magalon J, Chateau AL, Bertrand B, et al. DEPA classification: a proposal for standardising PRP use and a retrospective application of available devices. BMJ Open Sport Exerc Med. 2016;2(1):e000060. PMID: 27900152. DOI: 10.1136/bmjsem-2015-000060
3. Nie LY, Zhao K, Ruan J, Xue J. Effectiveness of Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis: A Meta-analysis of Randomized Controlled Clinical Trials. Orthop J Sports Med. 2021;9(3):2325967120973284. PMID: 33718505. DOI: 10.1177/2325967120973284
4. Berrigan W, Tao F, Kopcow J, 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;17(12):570-588. PMID: 39331322. DOI: 10.1007/s12178-024-09922-x

This article is patient education covering general principles and clinical considerations. It cannot replace an in-person examination. The effect and duration of regenerative injection treatment vary with individual tissue response, and efficacy is not guaranteed; whether it is suitable, which configuration to use and how many sessions are needed require in-person and imaging assessment. Injection may be followed by local soreness, bruising or temporary swelling. It is generally unsuitable during active infection, active malignancy, clotting disorders or pregnancy. To review your own situation, you are welcome to arrange an online consultation and individual assessment.