Advertisement

Platelet-Rich Plasma: The PAW Classification System

      Abstract

      Platelet-rich plasma (PRP) has been the subject of hundreds of publications in recent years. Reports of its effects in tissue, both positive and negative, have generated great interest in the orthopaedic community. Protocols for PRP preparation vary widely between authors and are often not well documented in the literature, making results difficult to compare or replicate. A classification system is needed to more accurately compare protocols and results and effectively group studies together for meta-analysis. Although some classification systems have been proposed, no single system takes into account the multitude of variables that determine the efficacy of PRP. In this article we propose a simple method for organizing and comparing results in the literature. The PAW classification system is based on 3 components: (1) the absolute number of Platelets, (2) the manner in which platelet Activation occurs, and (3) the presence or absence of White cells. By analyzing these 3 variables, we are able to accurately compare publications.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Arthroscopy
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Woodell-May J.E.
        • Ridderman D.N.
        • Swift M.J.
        • Higgins J.
        Producing accurate platelet counts for platelet rich plasma: Validation of a hematology analyzer and preparation techniques for counting.
        J Craniofac Surg. 2005; 16: 749-759
        • Brickson S.
        • Ji L.L.
        • Schell K.
        • Olabisi R.
        • St Pierre Schneider B.
        • Best T.M.
        M1/70 attenuates blood-borne neutrophil oxidants, activation, and myofiber damage following stretch injury.
        J Appl Physiol. 2003; 95: 969-976
        • Crinnion J.N.
        • Homer-Vanniasinkam S.
        • Parkin S.M.
        • Gough M.J.
        Role of neutrophil-endothelial adhesion in skeletal muscle reperfusion injury.
        Br J Surg. 1996; 83: 251-254
        • Diegelmann R.F.
        • Evans M.C.
        Wound healing: An overview of acute, fibrotic and delayed healing.
        Front Biosci. 2004; 9: 283-289
        • Dovi J.V.
        • He L.K.
        • DiPietro L.A.
        Accelerated wound closure in neutrophil-depleted mice.
        J Leukoc Biol. 2003; 73: 448-455
        • Grøgaard B.
        • Gerdin B.
        • Reikerås O.
        The polymorphonuclear leukocyte: Has it a role in fracture healing?.
        Arch Orthop Trauma Surg. 1990; 109: 268-271
        • Martin P.
        • Leibovich S.J.
        Inflammatory cells during wound repair: The good, the bad and the ugly.
        Trends Cell Biol. 2005; 15: 599-607
        • Schneider B.S.
        • Tiidus P.M.
        Neutrophil infiltration in exercise-injured skeletal muscle: How do we resolve the controversy?.
        Sports Med. 2007; 37: 837-856
        • Simpson D.M.
        • Ross R.
        The neutrophilic leukocyte in wound repair.
        J Clin Invest. 1972; 51: 2009-2023
        • Toumi H.
        • Best T.M.
        The inflammatory response: Friend or enemy for muscle injury?.
        Br J Sports Med. 2003; 37: 284-286
        • Tidball J.G.
        Inflammatory processes in muscle injury and repair.
        Am J Physiol Regul Integr Comp Physiol. 2005; 288: R345-R353
        • Redler L.H.
        • Thompson S.A.
        • Hsu S.H.
        • et al.
        Platelet-rich plasma therapy: A systematic literature review and evidence for clinical use.
        Phys Sports Med. 2011; 39: 42-51
      1. Kon E. PRP for the treatment of cartilage defects. Presented at the AAOS (American Academy of Orthopaedic Surgeons) Now 2011 PRP Forum, San Diego, CA, February 14, 2011.

        • Castillo T.N.
        • Pouliot M.A.
        • Kim H.J.
        • Dragoo J.L.
        Comparison of growth factor and platelet concentration from commercial platelet-rich plasma separation systems.
        Am J Sports Med. 2011; 39: 266-271
        • Kon E.
        • Filardo G.
        • Di Martino A.
        • Marcacci M.
        Platelet-rich plasma (PRP) to treat sports injuries: Evidence to support its use.
        Knee Surg Sports Traumatol Arthrosc. 2011; 19: 516-527
        • Wahlström O.
        • Linder C.
        • Kalén A.
        • Magnusson P.
        Variation of pH in lysed platelet concentrates influence proliferation and alkaline phosphatase activity in human osteoblast-like cells.
        Platelets. 2007; 18: 113-118
        • Borg T.
        • Modig J.
        Potential anti-thrombotic effects of local anesthetics due to their inhibition of platelet aggregation.
        Acta Anaesthesiol Scand. 2008; 29: 739-742
        • Mazzocca A.D.
        • McCarthy M.B.
        • Chowaniec D.M.
        • et al.
        Platelet-rich plasma differs according to preparation method and human variability.
        J Bone Joint Surg Am. 2012; 94: 308-316
        • Tanaka Y.
        • Kurashima K.
        • Saito H.
        • et al.
        In vitro short-term platelet adhesion on various metals.
        J Artif Organs. 2009; 12: 182-186
        • Michelson A.D.
        Platelets. Ed 2. Elsevier/Academic Press, San Diego2007
        • Grottum K.A.
        • Jorgensen L.
        • Jeremic M.
        Decrease in platelet surface charge during phagocytosis of polystyrene latex particles or thorium dioxide.
        Scand J Haematol. 1972; 9: 83-96
        • Arthrex
        ACP: Autologous conditioned plasma double syringe system.
        Arthrex, Naples, FL2011
        • Cascade Medical/MTF
        Releasing the power of growth factor healing.
        Cascade Medical/Musculoskeletal Transplant Foundation, Edison, NJ2008
        • Leitner G.C.
        • Gruber R.
        • Neumüller J.
        • et al.
        Platelet content and growth factor release in platelet-rich plasma: A comparison of four different systems.
        Vox Sang. 2006; 91: 135-139
        • Mazzucco L.
        • Balbo V.
        • Cattana E.
        • Guaschino R.
        • Borzini P.
        Not every PRP-gel is born equal.
        Vox Sang. 2009; 97: 110-118
        • Anitua E.
        • Aguirre J.J.
        • Algorta J.
        • et al.
        Effectiveness of autologous preparation rich in growth factors for the treatment of chronic cutaneous ulcers.
        J Biomed Mater Res B Appl Biomater. 2008; 84: 415-421
        • Sánchez M.
        • Anitua E.
        • Azofra J.
        • Aguirre J.J.
        • Andia I.
        Intra-articular injection of an autologous preparation rich in growth factors for the treatment of knee OA: A retrospective cohort study.
        Clin Exp Rheumatol. 2008; 26: 910-913
        • Sánchez M.
        • Anitua E.
        • Azofra J.
        • Andía I.
        • Padilla S.
        • Mujika I.
        Comparison of surgically repaired Achilles tendon tears using platelet-rich fibrin matrices.
        Am J Sports Med. 2007; 35: 245-251
        • Biomet
        GPS III platelet separation system process steps.
        Biomet, Warsaw, IN2009
        • Biomet
        GPS III platelet separation system.
        Biomet, Warsaw, IN2007
        • Eppley B.L.
        • Woodell J.E.
        • Higgins J.
        Platelet quantification and growth factor analysis from platelet-rich plasma: Implications for wound healing.
        Plast Reconstr Surg. 2004; 114: 1502-1508
        • Kevy S.V.
        • Jacobson M.S.
        Comparison of methods for point of care preparation of autologous platelet gel.
        J Extra Corpor Technol. 2004; 36: 28-35
        • Roukis T.S.
        • Zgonis T.
        • Tiernan B.
        Autologous platelet-rich plasma for wound and osseous healing: A review of the literature and commercially available products.
        Adv Ther. 2006; 23: 218
        • Harvest Technologies
        Developing technologies for accelerating healing, naturally.
        Harvest Technologies, Plymouth, MA2000
        • Sclafani A.P.
        • Romo T.R.
        • Ukrainsky G.
        • et al.
        Modulation of wound response and soft tissue ingrowth in synthetic and allogeneic implants with platelet concentrate.
        Arch Facial Plast Surg. 2005; 7: 163-169
        • Christensen K.
        • Vang S.
        • Brady C.
        • et al.
        Autologous platelet gel: An in vitro analysis of platelet-rich plasma using multiple cycles.
        J Extra Corpor Technol. 2006; 38: 249-253
        • Medtronic
        Magellan autologous platelet separator.
        Medtronic, Minneapolis, MN2005
        • Exactech
        Accelerate concentrating system platelet rich plasma preparation guide.
        Exactech, Gainesville, FL2010
        • Exactech
        Analysis of Accelerate platelet concentrating system: Preparation of concentrated platelet product.
        Exactech, Gainesville, FL2010
        • Exactech
        Accelerate PRP sport preparation technique.
        Exactech, Gainesville, FL2010
        • Sánchez M.
        • Anitua E.
        • Andia I.
        Poor standardization in platelet-rich therapies hampers advancement.
        Arthroscopy. 2010; 26: 725-726
      2. Haynesworth SE, Kadiyala S, Liang LN, et al. Mitogenic stimulation of human mesenchymal stem cells by platelet release suggest a mechanism for enhancement of bone repair by platelet concentrates. Presented at the 48th Meeting of the Orthopedic Research Society, Boston, MA, 2002.

        • Anitua E.
        • Andía I.
        • Sanchez M.
        • et al.
        Autologous preparations rich in growth factors promote proliferation and induce VEGF and HGF production by human tendon cells in culture.
        J Orthop Res. 2005; 23: 281-286
        • Anitua E.
        • Orive G.
        • Pla R.
        • Roman P.
        • Serrano V.
        • Andía I.
        The effects of PRGF on bone regeneration and on titanium implant osseointegration in goats: A histologic and histomorphometric study.
        J Biomed Mater Res A. 2009; 91: 158-165
        • Anitua E.
        • Sánchez M.
        • Nurden A.T.
        • et al.
        Platelet-released growth factors enhance the secretion of hyaluronic acid and induce hepatocyte growth factor production by synovial fibroblasts from arthritic patients.
        Rheumatology (Oxford). 2007; 46: 1769-1772
        • Anitua E.
        • Sánchez M.
        • Zalduendo M.M.
        • et al.
        Fibroblastic response to treatment with different preparations rich in growth factors.
        Cell Prolif. 2009; 42: 162-170
        • Sánchez M.
        • Anitua E.
        • Azofra J.
        • Prado R.
        • Muruzabal F.
        • Andia I.
        Ligamentization of tendon grafts treated with an endogenous preparation rich in growth factors: Gross morphology and histology.
        Arthroscopy. 2010; 26: 470-480
        • Sánchez M.
        • Anitua E.
        • Cugat R.
        • et al.
        Nonunions treated with autologous preparation rich in growth factors.
        J Orthop Trauma. 2009; 23: 52-59
        • Sánchez M.
        • Azofra J.
        • Anitua E.
        • et al.
        Plasma rich in growth factors to treat an articular cartilage avulsion: A case report.
        Med Sci Sports Exerc. 2003; 35: 1648-1652
        • Graziani F.
        • Ivanovski C.
        • Cei S.
        • Ducci F.
        • Tonetti M.
        • Gabriele M.
        The in vitro effect of different PRP concentrations on osteoblasts and fibroblasts.
        Clin Oral Implants Res. 2006; 17: 212-219
        • Torricelli P.
        • Fini M.
        • Filardo G.
        • et al.
        Regenerative medicine for the treatment of musculoskeletal overuse injuries in competition horses.
        Int Orthop. 2011; 35: 1569-1576
        • He H.T.
        • Majd M.E.
        • Holt R.T.
        • et al.
        Do autologous growth factors enhance transforaminal lumbar interbody fusion?.
        Eur Spine J. 2003; 12: 400-407
        • Weibrich G.
        • Hansen K.
        • Kleis W.
        • Buch R.
        • Hitzler W.E.
        Effect of platelet concentration in platelet-rich plasma on peri-implant bone regeneration.
        Bone. 2004; 34: 665-671
        • Giusti I.
        • Rughetti A.
        • D'Ascenzo S.
        • et al.
        Identification of an optimal concentration of platelet gel for promoting angiogenesis in human endothelial cells.
        Transfusion. 2009; 49: 771-778
        • Gruber R.
        • Varga F.
        • Fischer M.B.
        • Watzek G.
        Platelets stimulate proliferation of bone cells: Involvement of platelet-derived growth factor, microparticles and membranes.
        Clin Oral Implants Res. 2002; 13: 529-535
        • Choi B.H.
        • Zhu S.J.
        • Kim B.Y.
        • et al.
        Effect of platelet-rich plasma (PRP) concentration on the viability and proliferation of alveolar bone cells: An in vitro study.
        Int J Oral Maxillofac Surg. 2005; 34: 420-424
        • Nikolidakis D.
        • Jansen J.A.
        The biology of platelet-rich plasma and its application in oral surgery: Literature review.
        Tissue Eng Part B Rev. 2008; 14: 249-258
      3. Jo CH, Roh YH, Kim JE, et al. Optimizing platelet-rich plasma gel formation by varying time and gravitational forces during centrifugation. J Oral Implantol in press, available online 11 April, 2011.

        • Barrett S.
        • Erredge S.
        Growth factors for chronic plantar fasciitis.
        Podiatry Today. 2004; 17: 37-42
        • Dohan Ehrenfest D.M.
        • Rasmusson L.
        • Albrektsson T.
        Classification of platelet concentrates: From pure platelet-rich plasma (P-PRP) to leucocyte- and platelet-rich fibrin (L-PRF).
        Trends Biotechnol. 2009; 27: 158-167
        • Saad Setta H.
        • Elshahat A.
        • Elsherbiny K.
        • Massoud K.
        • Safe I.
        Platelet-rich plasma versus platelet-poor plasma in the management of chronic diabetic foot ulcers: A comparative study.
        Int Wound J. 2011; 8: 307-312
        • Rappl L.M.
        Effect of platelet rich plasma gel in a physiologically relevant platelet concentration on wounds in persons with spinal cord injury.
        Int Wound J. 2011; 8: 187-195
        • Frykberg R.G.
        • Driver V.R.
        • Carman D.
        • et al.
        Chronic wounds treated with a physiologically relevant concentration of platelet-rich plasma gel: A prospective case series.
        Ostomy Wound Manage. 2010; 56: 36-44
        • Moojen D.J.
        • Everts P.A.
        • Schure R.M.
        • et al.
        Antimicrobial activity of platelet-leukocyte gel against Staphylococcus aureus.
        J Orthop Res. 2008; 26: 404-410
        • Martin P.
        • D'Souza D.
        • Martin J.
        • et al.
        Wound healing in the PU.1 null mouse—Tissue repair is not dependent on inflammatory cells.
        Curr Biol. 2003; 13: 1122-1128
        • de Vos R.J.
        • Weir A.
        • van Schie H.T.
        • Verhaar J.A.
        • Weinans H.
        • van Schie H.T.
        No effects of PRP on ultrasonographic tendon structure and neovascularisation in chronic midpoint Achilles tendinopathy.
        Br J Sports Med. 2011; 45: 387-392
        • Mishra A.
        • Woodall J.
        • Vieira A.
        Treatment of tendon and muscle using platelet-rich plasma.
        Clin Sports Med. 2009; 28: 113-125
        • Harrison S.
        • Vavken P.
        • Kevy S.
        • Jacobson M.
        • Zurakowski D.
        • Murray M.M.
        Platelet activation by collagen provides sustained release of anabolic cytokines.
        Am J Sports Med. 2011; 39: 729-734
        • Mosesson M.W.
        • Siebenlist K.R.
        • Meh D.A.
        The structure and biological features of fibrinogen and fibrin.
        Ann N Y Acad Sci. 2001; 936: 11-30
        • Alsousou J.
        • Thompson M.
        • Hulley P.
        • Noble A.
        • Willett K.
        The biology of platelet-rich plasma and its application in trauma and orthopaedic surgery: A review of the literature.
        J Bone Joint Surg Br. 2009; 91: 987-996
        • Dohan D.M.
        • Choukroun J.
        • Diss A.
        • et al.
        Platelet-rich fibrin (PRF): A second-generation platelet concentrate.
        Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006; 101: e37-e44
        • Foster T.E.
        • Puskas B.L.
        • Mandelbaum B.R.
        • Gerhardt M.B.
        • Rodeo S.A.
        Platelet-rich plasma: From basic science to clinical applications.
        Am J Sports Med. 2009; 37: 2259-2272
        • Bir S.C.
        • Esaki J.
        • Marui A.
        • et al.
        Angiogenic properties of sustained release platelet-rich plasma: Characterization in-vitro and in the ischemic hind limb of the mouse.
        J Vasc Surg. 2009; 50: 870-879.e2
        • Batoni G.
        • Maisetta G.
        • Brancatisano F.L.
        • Esin S.
        • Campa M.
        Use of antimicrobial peptides against microbial biofilms: Advantages and limits.
        Curr Med Chem. 2011; 18: 256-279
        • Carrol R.J.
        • Arnoczky S.P.
        • Graham S.
        • et al.
        Characterization of autologous growth factors.
        Musculoskeletal Transplant Foundation, Edison, NJ2005
        • Fufa D.
        • Shealy B.
        • Jacobson M.
        • Kevy S.
        • Murray M.M.
        Activation of platelet-rich plasma using soluble type I collagen.
        J Oral Maxillofac Surg. 2008; 66: 684-690
        • Lyras D.N.
        • Kazakos K.
        • Georgiadis G.
        • et al.
        Does a single application of PRP alter the expression of IGF-I in the early phase of tendon healing?.
        J Foot Ankle Surg. 2011; 50: 276-282
        • Hechtman K.S.
        • Uribe J.W.
        • Botto-vanDemden A.
        • Kiebzak G.M.
        Platelet-rich plasma injection reduces pain in patients with recalcitrant epicondylitis.
        Orthopedics. 2011; 34 (92-92)
        • Thanasas C.
        • Papadimitriou G.
        • Charalambidis C.
        • Paraskevopoulos I.
        • Papanikolaou A.
        Platelet-rich plasma versus autologous whole blood for the treatment of chronic lateral elbow epicondylitis: A randomized controlled clinical trial.
        Am J Sports Med. 2011; 39: 2130-2134
        • Peerbooms J.C.
        • Sluimer J.
        • Bruijn D.J.
        • Gosens T.
        Positive effect of an autologous platelet concentrate in lateral epicondylitis in a double-blind randomized controlled trial: Platelet-rich plasma versus corticosteroid injection with a 1-year follow-up.
        Am J Sports Med. 2010; 38: 255-262
        • Gosens T.
        • Peerbooms J.C.
        • van Laar W.
        • den Oudsten B.L.
        Ongoing positive effect of platelet-rich plasma versus corticosteroid injection in lateral epicondylitis: A double-blind randomized controlled trial with 2-year follow-up.
        Am J Sports Med. 2011; 39: 1200-1208
        • Mishra A.
        • Pavelko T.
        Treatment of chronic elbow tendinosis with buffered platelet-rich plasma.
        Am J Sports Med. 2006; 34: 1774-1778
        • de Jonge S.
        • de Vos R.J.
        • Weir A.
        • et al.
        One-year follow-up of platelet-rich plasma treatment in chronic Achilles tendinopathy: A double-blind randomized placebo-controlled trial.
        Am J Sports Med. 2011; 39: 1623-1629
        • Schepull T.
        • Kvist J.
        • Norrman H.
        • Trinks M.
        • Berlin G.
        • Aspenberg P.
        Autologous platelets have no effect on the healing of human Achilles tendon ruptures: A randomized single-blind study.
        Am J Sports Med. 2011; 39: 38-47
        • Filardo G.
        • Presti M.L.
        • Kon E.
        • Marcacci M.
        Nonoperative biological treatment approach for partial Achilles tendon lesion.
        Orthopedics. 2010; 33: 120-123
        • Filardo G.
        • Kon E.
        • Della Villa S.
        • Vincentelli F.
        • Fornasari P.M.
        • Marcacci M.
        Use of platelet-rich plasma for the treatment of refractory jumper's knee.
        Int Orthop. 2010; 34: 909-915
        • Kon E.
        • Filardo G.
        • Delcogliano M.
        • et al.
        Platelet-rich plasma: New clinical application: A pilot study for treatment of jumper's knee.
        Injury. 2009; 40: 598-603
        • Jo C.H.
        • Kim J.E.
        • Yoon K.S.
        • et al.
        Does platelet-rich plasma accelerate recovery after rotator cuff repair?.
        Am J Sports Med. 2011; 39: 2082-2090
        • Randelli P.
        • Arrigoni P.
        • Ragone V.
        • Aliprandi A.
        • Cabitza P.
        Platelet rich plasma in arthroscopic rotator cuff repair: A prospective RCT study, 2-year follow-up.
        J Shoulder Elbow Surg. 2011; 20: 518-528
        • Castricini R.
        • Longo U.G.
        • De Benedetto M.
        • et al.
        Platelet-rich plasma augmentation for arthroscopic rotator cuff repair: A randomized controlled trial.
        Am J Sports Med. 2011; 39: 258-265
        • Randelli P.S.
        • Arrigoni P.
        • Cabitza P.
        • Volpi P.
        • Maffulli N.
        Autologous platelet rich plasma for arthroscopic rotator cuff repair.
        Disabil Rehabil. 2008; 30: 1584-1589
        • Barber F.A.
        • Hrnack S.A.
        • Snyder S.J.
        • Hapa O.
        Rotator cuff repair healing influenced by platelet-rich plasma construct augmentation.
        Arthroscopy. 2011; 27: 1029-1035
        • Everts P.A.
        • Devilee R.J.
        • Brown Mahoney C.
        • et al.
        Exogenous application of platelet-leukocyte gel during open subacromial decompression contributes to improved patient outcome.
        Eur Surg Res. 2008; 40: 203-210
        • Kon E.
        • Mandelbaum B.
        • Buda R.
        • et al.
        Platelet-rich plasma intra-articular injection versus hyaluronic acid viscosupplementation as treatments for cartilage pathology: From early degeneration to osteoarthritis.
        Arthroscopy. 2011; 27: 1490-1501
        • Kon E.
        • Buda R.
        • Filardo G.
        • et al.
        Platelet-rich plasma: Intra-articular knee injections produced favorable results on degenerative cartilage lesions.
        Knee Surg Sports Traumatol Arthrosc. 2010; 18: 472-479
        • Silva A.
        • Sampaio R.
        Anatomic ACL reconstruction: Does the platelet-rich plasma accelerate tendon healing?.
        Knee Surg Sports Traumatol Arthrosc. 2009; 17: 676-682
        • Peerbooms J.C.
        • de Wolf G.S.
        • Colaris J.W.
        • Bruijn D.J.
        • Verhaar J.A.
        No positive effect of autologous platelet gel after total knee arthroplasty.
        Acta Orthop. 2009; 80: 557-562