PRP questions with plain answers

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1. In a controlled laboratory study, blood from five healthy donors was processed through three commercial PRP systems (MTF Cascade, Arteriocyte Magellan, Biomet GPS III). Platelet, red-cell and TGF-beta1 concentrations did not differ significantly between systems, but white-cell counts and PDGF-alpha-beta, PDGF-beta-beta and VEGF concentrations differed significantly across all three. Cascade produced leukocyte-poor PRP while GPS III and Magellan produced leukocyte-rich PRP with correspondingly higher white cells and growth factors.

   Castillo TN, Pouliot MA, Kim HJ, et al. — Comparison of growth factor and platelet concentration from commercial platelet-rich plasma separation systems. American Journal of Sports Medicine, 2011. DOI: 10.1177/0363546510387517.

2. The PAW classification was proposed because PRP preparation protocols 'vary widely between authors and are often not well documented in the literature, making results difficult to compare or replicate'. It sorts preparations by three variables: the absolute number of Platelets, the manner of Activation, and the presence or absence of White cells - the three levers that make two injections both called 'PRP' materially different products.

   DeLong JM, Russell RP, Mazzocca AD — Platelet-rich plasma: the PAW classification system. Arthroscopy, 2012. DOI: 10.1016/j.arthro.2012.04.148.

3. A systematic review that screened 876 studies and extracted standardised data from 33 commercially available PRP systems and protocols found that final product concentrations of platelets, white cells and growth factors varied widely between systems, as did the preparation protocols themselves. Platelet concentration correlated directly with the volume of blood drawn and with the centrifugal force of the device. The authors called the heterogeneity between separation systems something that 'must be resolved for proper study of this promising treatment'.

   Fadadu PP, Mazzola AJ, Hunter CW, et al. — Review of concentration yields in commercially available platelet-rich plasma (PRP) systems: a call for PRP standardization. Regional Anesthesia and Pain Medicine, 2019. DOI: 10.1136/rapm-2018-100356.

4. A systematic review of 105 clinical PRP studies in orthopaedics published 2006-2016 found that only 11 (10%) described the preparation protocol clearly enough for another investigator to repeat it, and only 17 (16%) reported any quantitative metric of the final PRP composition. The authors concluded that the current reporting of PRP preparation and composition does not allow the PRP products actually delivered to patients to be compared between studies.

   Chahla J, Cinque ME, Piuzzi NS, et al. — A Call for Standardization in Platelet-Rich Plasma Preparation Protocols and Composition Reporting: A Systematic Review of the Clinical Orthopaedic Literature. Journal of Bone and Joint Surgery (American), 2017. DOI: 10.2106/JBJS.16.01374.

5. A prospective fixed-sequence controlled laboratory study in healthy men found that daily low-dose aspirin significantly reduced release of VEGF, PDGF-AB and TGF-beta1 from freshly isolated leukocyte-rich PRP when activated with arachidonic acid. This is the mechanistic basis for the routine instruction to review antiplatelet and NSAID use before a PRP draw - and the authors noted clinical studies are still needed to establish how much this matters in vivo.

   Jayaram P, Yeh P, Patel SJ, et al. — Effects of Aspirin on Growth Factor Release From Freshly Isolated Leukocyte-Rich Platelet-Rich Plasma in Healthy Men: A Prospective Fixed-Sequence Controlled Laboratory Study. American Journal of Sports Medicine, 2019. DOI: 10.1177/0363546519827294.

6. In the RESTORE trial - the largest placebo-controlled PRP trial in knee osteoarthritis - 288 adults aged 50+ with symptomatic Kellgren-Lawrence grade 2-3 medial knee OA received three weekly intra-articular injections of leukocyte-poor PRP from a commercial system or saline placebo. At 12 months the mean change in knee pain was -2.1 points with PRP versus -1.8 with saline (difference -0.4; 95% CI -0.9 to 0.2; P=.17) against a minimum clinically important difference of 1.8, and the change in medial tibial cartilage volume was -1.4% versus -1.2% (difference -0.2%; 95% CI -1.9% to 1.5%; P=.81). Twenty-nine of 31 prespecified secondary outcomes showed no significant between-group difference. The authors concluded the findings do not support use of PRP for knee OA.

   Bennell KL, Paterson KL, Metcalf BR, 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. DOI: 10.1001/jama.2021.19415.

7. The devices used to spin PRP at the point of care are cleared by FDA as clinical centrifuges, product code JQC, a Class I device under 21 CFR 862.2050 - for example the Biomet GPS Platelet Separation Kit (K030555, cleared 2003) and the Harvest SmartPrep2 / SmartPrep Platelet Concentration System (K103340, cleared 2010). That clearance covers the equipment that separates blood. It is not an FDA approval of platelet-rich plasma as a treatment for osteoarthritis, tendinopathy or any other orthopedic condition, and copy must never blur the two.

   U.S. Food and Drug Administration (Center for Devices and Radiological Health) — 510(k) Premarket Notification database and Product Classification: JQC, Centrifuges (Micro, Ultra, Refrigerated) For Clinical Use, 21 CFR 862.2050. FDA accessdata (CDRH device databases), 2003.