Platelet-rich plasma is not one product. “Leukocyte-poor” and “leukocyte-rich” describe how many white blood cells the preparation retains, and that single variable changes the biology of what is injected.
What it does not appear to change, at least in knee osteoarthritis, is the clinical result. In direct comparisons the two categories have not separated on pain or function — though leukocyte-rich preparations have been associated with more local reactions afterward. Here is what the evidence actually says, and why the label alone still does not tell you what you are receiving.
What the two categories mean
Both preparations start with your own blood. The difference is what happens to the white blood cell fraction during processing: leukocyte-poor preparations remove or filter most of it out, leukocyte-rich preparations keep it in. In the largest randomized comparison, the leukocyte-poor arm was produced with a leukodepletion filter, and the resulting mean leukocyte concentrations differed by roughly five orders of magnitude between the two arms [2].
What leukocytes actually do
Leukocytes are part of the inflammatory phase of healing, and inflammation is not automatically the enemy. One mechanistic paper argues that both platelets and leukocytes matter to repair, specifically because macrophages can switch from the M1 to the M2 fraction, and proposes on that basis that buffy-coat-derived preparations may be more beneficial than detrimental [4].
That is a proposal about mechanism, not a demonstrated clinical advantage. It is a reason to take formulation seriously; it is not a reason to assume one category wins.
What the knee osteoarthritis evidence shows
The randomized head-to-head trial
A double-blind randomized controlled trial (Level 1) enrolled 192 patients with symptomatic knee osteoarthritis, Kellgren-Lawrence grade 1 to 3, and allocated them to three weekly injections of either leukocyte-rich or leukocyte-poor platelet-rich plasma [2].
No differences between the groups were observed in absolute values or in improvement of clinical scores across any follow-up interval. Mean subjective International Knee Documentation Committee scores rose from 45.6 to 60.7 in the leukocyte-rich group and from 46.8 to 62.9 in the leukocyte-poor group at 12 months (P = .626). Fifteen mild adverse events, knee pain or swelling, were reported: 12.2% with leukocyte-rich and 4.7% with leukocyte-poor (P = .101). Failures were 7.8% versus 3.5% (P = .331). The authors concluded the presence of leukocytes did not significantly affect the clinical results [2].
What the pooled reviews add
A systematic review and meta-analysis of 32 studies in knee osteoarthritis found both preparations improved pain and function above the minimal clinically important difference, with no significant difference between groups at 3, 6 or 12 months. Local adverse reactions, however, did differ: pain was significantly more common after leukocyte-rich injection (odds ratio 1.64; 95% CI 1.29 to 2.10; P = .01), as was swelling (odds ratio 1.56; 95% CI 1.22 to 1.99; P = .02) [3].
A 2026 systematic review analyzing 11 in vivo and in vitro studies reached a compatible conclusion: current evidence is insufficient to determine whether adding leukocytes provides a clinical benefit in osteoarthritis, results generally show no significant differences between the two, and there is no conclusive evidence that local reactions are directly caused by leukocytes [1].
Read together, that is an honest and slightly uncomfortable picture. Formulation changes the biology. It has not yet been shown to change the outcome you care about.
Why the label is not enough
Leukocyte content is one variable among several. Preparation also differs by centrifugation time, relative centrifugal force, the volume of blood drawn, the anticoagulant used — ethylenediaminetetraacetic acid and citrate are the most common, and the literature disagrees about which is preferable — and the resuspension medium. Standardized protocols for preparation were lacking, and a proposed standard published in 2022, built from 40 healthy volunteers, examined centrifugation time, relative centrifugal force and required blood volume specifically to address that gap [1].
This is why two trials can both report using “leukocyte-rich” platelet-rich plasma and not be describing the same product. It is also why the useful question in the room is not which category you are getting, but what the preparation is designed to achieve for your tissue.
How formulation fits an evaluation at Regen.MD
At Regen.MD in St. Louis, formulation is decided after the diagnosis, not before it. Our evaluation establishes the tissue target and the stage of the problem first; the preparation is matched to that.
The orthobiologics we offer include intra-articular and tendon platelet-rich plasma in both leukocyte-poor and leukocyte-rich variants, intraosseous and subchondral platelet-rich plasma, bone marrow aspirate concentrate, Lipogems, and intradiscal orthobiologics. For advanced knee osteoarthritis, platelet-rich plasma is discussed as a bridge therapy before joint replacement; no orthobiologic used here is claimed to rebuild lost cartilage. When conservative measures have been exhausted, surgery is part of the pathway, and Dr. Gurpreet Singh Padda, MD, MBA, MHP is a surgeon.
Get the formulation matched to your diagnosis, not to a label
Regen.MD begins with a paid, physician-led Clinical Evaluation — a review of your history, imaging, and metabolic data, and a written roadmap for what to do next. Evaluation is contingent upon review of your data.
Questions? Call (314) 295-3000 or text (314) 886-5902.
Regen.MD, 4477 Woodson Rd, Suite 103, St. Louis, MO 63134, next to St. Louis Lambert International Airport.
What this practice actually uses
The formulation questions above are not left open here. Regen.MD prepares platelet-rich plasma leukocyte-poor — no white blood cells and no red blood cells — activated with calcium chloride, at a platelet concentration of two to three times baseline, with higher dosing in the six to twelve times range.
The target is a measured dose of more than ten billion platelets delivered per joint. Measured rather than assumed: platelet yield varies between patients and between draws, which is why a protocol expressed only as a multiple of baseline can deliver very different absolute doses to two people on the same day. That is the practice’s specification, not a finding from any single trial.
Frequently asked questions
Is leukocyte-rich or leukocyte-poor platelet-rich plasma better for knee osteoarthritis?
Head to head, neither has separated cleanly. A Level 1 randomized trial of 192 patients found no difference in clinical scores at any follow-up interval, and a 2026 systematic review concluded the evidence is insufficient to say that adding leukocytes produces a clinical benefit in osteoarthritis. Which preparation fits your case depends on the tissue being treated, which is part of what we sort out when we evaluate the conditions we treat.
Does leukocyte-rich platelet-rich plasma cause more swelling or pain after the injection?
A systematic review of 32 studies in knee osteoarthritis found local adverse reactions for pain and for swelling were both significantly more common after leukocyte-rich injections than leukocyte-poor ones. A later review noted there is no conclusive evidence that those reactions are caused by the leukocytes themselves. Our education library covers what to expect after an injection.
Why do two clinics using the same label produce different platelet-rich plasma?
Because the label describes one variable and the preparation involves many: centrifugation time, relative centrifugal force, the volume of blood drawn, the anticoagulant, the resuspension medium, and whether leukocytes are filtered out. Standardized preparation protocols were lacking for years. We walk through how each orthobiologic is prepared before anything is scheduled.
What should I ask about formulation at my evaluation?
Ask which leukocyte category is being targeted and why, whether the target is intra-articular, intraosseous or tendon, and how response and adverse reactions will be monitored afterward. Those are questions Dr. Gurpreet Singh Padda, MD, MBA, MHP expects and answers directly.
Sources
- Martín-Vega M, Gómez-Carrión Á, Zaragoza-García I, Ortuño-Soriano I, et al. “Leukocyte-rich versus leukocyte-poor platelet-rich plasma for Osteoarthritis: A systematic review.” Regenerative Therapy, 2026. https://pmc.ncbi.nlm.nih.gov/articles/PMC12955565/ — referenced for the 11 analyzed studies, the insufficiency of evidence on added leukocytes, the absence of conclusive evidence linking local reactions to leukocytes, and the preparation variables including centrifugation parameters, anticoagulant choice and resuspension medium.
- Di Martino A, Boffa A, Andriolo L, Romandini I, Altamura SA, Cenacchi A, Roverini V, Zaffagnini S, Filardo G. “Leukocyte-Rich versus Leukocyte-Poor Platelet-Rich Plasma for the Treatment of Knee Osteoarthritis: A Double-Blind Randomized Trial.” American Journal of Sports Medicine, 2022;50(3):609-617. https://pubmed.ncbi.nlm.nih.gov/35103547/ — referenced for the 192-patient population, Kellgren-Lawrence grade 1 to 3 inclusion, three weekly injections, the leukodepletion filter, the International Knee Documentation Committee scores, the adverse-event and failure rates, and the conclusion on leukocytes.
- Kim JH, Park YB, Ha CW, Roh YJ, et al. “Adverse Reactions and Clinical Outcomes for Leukocyte-Poor Versus Leukocyte-Rich Platelet-Rich Plasma in Knee Osteoarthritis: A Systematic Review and Meta-analysis.” Orthopaedic Journal of Sports Medicine, 2021. https://pmc.ncbi.nlm.nih.gov/articles/PMC8255589/ — referenced for the 32 included studies, improvement above the minimal clinically important difference in both groups, the absence of intergroup difference at 3, 6 and 12 months, and the odds ratios for post-injection pain and swelling.
- Lana JF, Huber SC, Purita J, Tambeli CH, Santos GS, Paulus C, Annichino-Bizzacchi JM. “Leukocyte-rich PRP versus leukocyte-poor PRP — The role of monocyte/macrophage function in the healing cascade.” Journal of Clinical Orthopaedics and Trauma, 2019;10(Suppl 1):S7-S12. https://pubmed.ncbi.nlm.nih.gov/31700202/ — referenced for the proposed role of the inflammatory phase, macrophage M1 to M2 plasticity, and the authors’ proposal regarding buffy-coat-derived preparations.