Level V Evidence

Platelet-Rich Plasma: The PAW Classification System

Jeffrey M. DeLong, B.Sc., Ryan P. Russell, M.A., and Augustus D. Mazzocca, M.S., M.D.

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 theorthopaedic community. Protocols for PRP preparation vary wide!)' between authors and are oftennot well documented in the literature, making results difficult to compare or replicate. A classificationsystem is needed to more accurately compare protocols and results and effectively group studiestogether for meta-analysis. Although some classification systems have been proposed, no singlesystem takes into account the multitude of variables that determine the efficacy of PRP. In this articlewe propose a simple method for organizing and comparing results in the literature. The PAWclassification system is based on 3 components: (1) the absolute number of Platelets, .(2) the mannerin which platelet Activation occurs, and (3) the presence or absence of White cells. By analyzingthese 3 variables, we are able to accurately compare publications.

Despite the promising effects of platelet-rich plasma(PRP) therapy, most studies conducted have lacked

accurate measurements and documentation of the PRPcomponents and delivery methods used. This lack ofstandardization and consistency is prevalent throughoutthe literature and has frustrated attempts to compareresults between articles. To determine the efficacy ofPRP from system to system and patient to patient, thePRP components and the means by which they aredelivered to the target tissue site should be identified anddocumented.1 Without these fundamental prerequisites,

From the Medical University of South Carolina (J.M.D.),Charleston, South Carolina; and Department of Orthopaedic Sur-gery, University of Connecticut (R.P.R., A.D.M.), Farmington,Conneciicut, U.S.A.

The authors report the following conflict of interest in relation tothis article: A.D.M. received research support and is a consultantfor Arthrex, Inc., Naples, Florida.

Received March 20, 2012; accepted April 25, 2012.Address correspondence to Augustus D. Mazzccca, M.S., M.D.,

Department of Orthopaedic Surgery, University of Connecticut, Med-ical Arts and Research Building, Room 4017, 263 Farmington Ave,Farmington, CT 06034-4037,' U.S.A. E-mail: admazzocca@yahoo, com

© 2012 by the Arthroscopy Association of North America0749-8063/12184/$36.00http://dx.doi.Org/10.1016/j.anhro.2012.Q4.148

the evolution of PRP as a safe and effective treatment fororthopaedic disorders may not progress efficiently.

IDENTIFYING CONTENT OF PRP

Several essential factors exist that need to be identifiedto adequately determine the effects of PRP treatment.

• The most essential factor is to ensure accurate anddefinitive concentration measurements of platelets.Without precise quantification of the cellular compo-nents, validation and accurate comparison of studieswill remain extremely difficult, ultimately impeding dis-covery of optimum dosing. Many studies published inthe recent literature lack this most basic requirement.

• The presence or absence of platelet activators, as wellas the type of activator used, is another importantelement requiring documentation. The way in whichthe platelets are applied to the tissue will undoubtedlyaffect the response of the tissue. For example, anexogenous platelet activator may be necessary to gen-erate a clot in certain procedures, whereas endogenousplatelet activation without the use of an external clot-ting factor may be ideal in other indications.

• Whether the administered PRP treatment includeshighly concentrated leukocytes above baseline

Arthroscopy: The Journal of Arthroscopic and Related Surgery, Vol 28, No 7 (July), 2012: pp 99S-I009

PRESIDENTIAL ADDRESS 997

cepted the responsibility to transfer the orb with pas-sion and determination, ensuring an even brighter andstronger future for those that follow.

I'll share a few final thoughts in closing.-A numberof individuals have come up to me and stated withconfidence that, "one of the best days of your life isthe day you become immediate past president!" Withone exception, nothing could be further from the truthfor me. This has been the most enjoyable and reward-ing year of my professional career. The opportunity towork with colleagues of great talent and a desire togenuinely contribute to the betterment of the organi-zation has been truly inspiring. What more could oneask for than to roll up your sleeves daily with friendswho want nothing more than to serve our organizationwell? I mentioned one exception—my stepping downmeans that Dr. Nick Sgaglione assumes the presi-dency of The Arthroscopy Association of NorthAmerica. I could not be more excited for his tenure.He is a man of immense talent, great character, and isone of the most outstanding natural leaders I have evermet. Dr. Thomas Byrd will follow Nick and is a man

wise beyond his years, respected throughout the worldfor his contributions to hip arthroscopy, and is theepitome of a "Southern Gentlemen." This organiza-tion could not be in better hands.

So, I am able to stand before you today and makethree statements with great certainty. First, the LadyAANA is in robust and radiant health. Secondly, thetrade winds are fair for the continued exploration foreducational treasures. Finally, there is no finer groupof individuals to transfer the golden orb of AANA'sculture to the next generation of young orthopaedicsurgeons than those of you sitting in this audiencetoday!

I offer my sincere thanks to you for the opportunityto serve as your president this past year.

RICHARD L. ANGELO, M.D.

Address correspondence and reprint requests to Richard L. Angela,M.D., 12911 120th Ave NE, Bldg H, Suite 210, Kirldand, WA 98034.E-mail: rlamdortho@comca.ft.net.

PLATELET-RICH PLASMA CLASSIFICATION 999

TABLE 1. Plasma-Based and Buffy Coat-Based PRP Systems

Device Name

Plasma-based PRP systemsArthrex (Naples, FL)/

ACP (Edison, NJ)Cascade/MTF Fibrinet

BTI (Vitoria-Gasteiz, Spain)/PRGF

Buffy coat-based PRP systemsBiomet (Warsaw, IN)

GPS II/IIIHarvest (Plymouth, MA)

SmartPReP 2/DePuy(Warsaw, IN) Symphony II

Arteriocyte Medtronic(Minneapolis, MN)/Magellan

Emcyte (Fort Myers, FL)/Genesis CS/Exactech(Gainsville, FL) Accelerate

CentrifugeTime (min)

5

6 (plasma)21 (clot)

S

12-15

12-15

14-20

12

Initial BloodVolume

(mL)

16

9

9

30 or 60

20 or 60

30 or 60

30 or 60

Final PRPVolume

(mL)

4-7

4.5 (plasma)2 (clot)

2-3

3 or 6

3 or 7- 10

3-10

3 or 10

PlateletConcentration From

• Baseline

2X-3X

1.3X-1.7X (plasma)

2X-3X

2X-SX

3X-7X

3X-7X

7X-10X

WBC Content

Minimal to none

Minimal to none

Minimal to none

Increased overbaseline

Increased overbaseline

Increased overbaseline

Increased overbaseline

References

22

14, 23-25

26-28

29-33

24, 32-35

14, 33, 36, 37

3S-40

Abbreviations: ACP, autologous conditioned platelets; BTI, Biotechnologymusculoskeletal transplant foundation; PRGF, platelet rich growth factor.

Institute; GPS, gravitational platelet separation; MTF,

levels or leukocyte-deficient PRP below baselineshould also be documented. This will identify whichtype of PRP system was used, plasma based or buffycoat. Buffy-coat systems contain both red blood cells(RBCs) and white blood cells (WBCs), whereas plas-ma-based systems exclude them. There is consid-erable debate over the necessity of includingwhite cells, with several studies suggesting thatthey may in fact be harmful to the healing pro-cess.2'11 Neutrophils, in particular, have been hy-pothesized to impede healing. It is likely that theneed to include WBCs in the PRP preparationwill vary by indication, and the WBC concentra-tion should be noted as above or below baselinein the "Methods" section of articles. Further iden-tifying neutrophil levels above or below bas'elmem'a^proye^to be a key IFl;gJvjn.gI^surrounding the efficacy of PRP richjr^ieukp-cytes.

• IiTa33ItIon to documentation of the components ofthe PRP end product, it is also important to recordthe delivery technique and whether additional fac-tors were distributed to the tissue site.

UNDERSTANDING PRP METHODSAND SYSTEMS

PRP can be manufactured in 2 basic formats: plasma-based and buffy-coat preparations. Both begin with

whole blood but differ in the centrifugation process,which isolates and concentrates different blood-cellcomponents.12

Plasma-based methods work to isolate only plasmaand platelet components and remove WBCs. Protocolsfor these preparations leave some platelets behind andfocus on intentionally excluding leukocytes, which arethought to be detrimental to the healing process.2"11 Themain goal of this method is to capture only plateletsduring the centrifugation; thus a slower and shorter spinregimen is used. This yields platelet concentrations typ-ically around 2X to 3X those of baseline whole bloodlevels (300,000 to 500,000 platelets//^) (Table 1).

Buffy coat-based methods isolate a platelet-poorplasma layer and a buffy-coat layer, which contains bothleukocytes and erythrocytes. Protocols for buffy-coatsystems seek to capture all available platelets during thecentrifugation and obtain a high concentration of WBCs;thus high spin rates and long spin regimens are used.Leukocytes and RBCs are harvested in an effort to obtainthe highest platelet concentration levels possible. Thetypical platelet concentration yields are between 3 X and8X those of baseline levels (500,000 to 1,500,000 plate-lets//^) (Table 1).

To complicate comparisons, each commercially avail-able PRP system uses a different spin protocol. Proto-cols, number and length of spins, platelet and leukocyteconcentrations, and delivery platform vary between these

1000 J. M. DELONG ET AL.

devices, making no 2 PRP products identical (Table 1).These variances lead to different amounts of. anabolicand catabolic proteins released to the target tissues afterinjection.13 For instance, Castillo et al.14 tested 3 differ-ent PRP separation systems, and each system yielded asimilar platelet concentration (approximately 600,000platelets//xL) and RBC, active transforming growth fac-tor (TGF) j3I, and fibrinogen levels. However, eachsystem produced significantly different levels of platelet-derived growth factor (PDGF) AB, PDGF-BB, vascularendothelial growth factor (VEGF), and WBC concentra-tion. Although the effects of these bioactive factors ontissue were not tested, it is possible that these variationscould result in considerable and dramatically distincteffects on healing.12 Lack of standardization of PRPpreparations may therefore lead to inconsistent results inthe literature.15

Additives also alter the content and effect of PRP.For example, anticoagulants and local jmesthetics alterthe pH of PRP; understanding the effect of this alter-ation on tissue response is important. Variations in pHhave been shown to affect in vitro proliferation, andconsideration must be given to the desired responsebefore choosing to mix PRP with an additive.16*17

Local anesthetics, in particular, appear to jjroduce anegative; effect_6ii~PRPjre^ment in_yitro _and_ shouldie avoided when possible.17-18

PRP can even be altered by the metals used in medicaldevices or implants as well as the centrifuge material.Tanaka et al.19 studied the effects that various metals hadon platelet adhesion. The study found that platelet adhe-sion and aggregation can both be inhibited and enhancedby different types of metal. Test tube materials are alsoimportant. Michelson20 reported in his comprehensivebook on platelets that polypropylene .tubes are.superior toeither polystyrene or polycarbonate when used.for plate-let preparation and/or storage. In addition, he noted thatuncoated glass may artificially activate platelets and af-fect results.20 A study conducted by Grottum et al.21

determined the effect of polystyrene particles on PRP.Incubation of PRP with polystyrene particles inducedsurface contact between platelets and particles, uptake ofparticles, and changes in platelet morphology. After in-jection into rabbits, Grottum et al, identified increasedplatelet aggregation, which may have resulted from areduction in platelet surface charge due to interactionwith polystyrene.21 For these reasons, it is imperativethat the protocol chosen to manufacture PRP in eachstudy be strictly adhered 'to, and materials cannot bereefy substituted.

UNDERSTANDING CELLULAR COMPONENTS

Platelet Concentration

Few studies have compared the healing effects ofdifferent PRP platelet concentrations for the sameindication.14*41 This may prove to be the most signif-icant aspect in identifying the true effectiveness ofPRP and in choosing the proper protocol.

Low: Less Than IX (Less Than Baseline): Plate-let concentrations below baseline may not allow for asufficient cellular response.42 Often used as a control,platelet-poor plasma has only shown the sk'ghtest benefit.

Moderate: Greater Than Ix to Less Than 4x(Greater Than Baseline to 750,000 platelets//*!,):Plasma-based PRP systems typically produce plateletconcentrations between baseline and 3X baseline. Theabsolute platelet number obtained by this method isgenerally equal to or less than 750,000 platelets/jtL.

In vitro, in vivo, and clinical studies have beenconducted and published by Anitua and Sanchez, aswell as their colleagues, showing jhe.effectivenessof PRP with a platelet concentration of 2X to3 X .26.23.43-49 Sanchez et al.28 injected exogenouslyactivated PRP with a 3X platelet concentration intosurgically repaired human Achilles tendons. Theyfound significant improvement and an earlier return tosports as compared with the control group. The sameresearchers performed an uncontrolled retrospectivecase study in which they treatedj_6 aseptic nonunionsintraoperatively with a moderate PRP platelet concen-tration (2X to 3X) with a bone, allograft and anautologous fibrin membrane. All subjects went on tobony union.47 Another study showed enhanced tendongraft ligamentization during anterior cruciate ligamentsurgery.41 Histology at the 6- and 24-month marksshowed increased connective tissue remodeling whencompared with the untreated grafts.

Anitua-and Sanchez are not the only researchers whohave"shown positive-responses'to PRP in the 2X to 3Xbaseline range. Graziani et al.50 evaluated the effect of ,PRP on the function of osteoblasts and fibroblasts^Aftera 72-hour incubation period, the 2.5X (approximately55MjOO_piatelets//xL') PPJ^grnup-resulted in a-statisti-cal 1 y-sigfiincantrfncrectsti in cblr count[orrosteubl;ibU> and

control. The authors concluded, that a platelet concentra-tion gf 2,5X^y-ialded-ep^rmal rcsnlteT-feraddition. Torri-celli et al.51 evaluated the effect of PRP for the treatmentof musculoskeletal overuse injuries in competitionhorses. With the placebo effect nullified, they found thatPRP with a platelet concentration of 750,000 plate-

PLATELET-RICH PLASMA CLASSIFICATION 1001

lets/,uL accelerated healing and allowed an earlier returnto competition.

High: 4X to 6x (>750,000 to 1,800,000 platelets/juiL): Literature suggests that successful buffy coat-based PRP treatments typically produce platelet con-centrations greater than 3 X and primarily in the 4X to6X range.14-24*32 The absolute platelet number is gen-erally greater than 750:000 to 1,800,000 platelets/^L.Successful reports in this range include that of He etal.,52 who found accelerated bone healing with PRPplatelet concentrations of approximately 4X to 5Xversus controls in patients who underwent transforma-tional lumbar interbody fusions. An in vivo rabbitstudy conducted by Weibrich et al.^ analyzed theeffect of platelet count in PRP on boae_r&gsneration.They found significant bone regeneration with a plate-let concentration up to 6X (1,729,000 platelets//xL).Giusti et al.54 studied endothelial cells and found thatthe optimal concentration for cell proliferation was

_ _Super: Greater Than 6x (>1,800,000 platelets/

:- Concenfaations— too— h-igb__-rriay h^dgjrjmeiital-Overwhelming the healing milieu with an excessiveamount of platelets may lead_tojirjoj}tasis, growth faster

•preceptor downregulation, and receptor desensitization,whicrTrnay result in a paradoxical inhibitory effect.42™5

Several studies have shown this. ..Weibrich et al.53

showed that highly concentrated platelets (6X to 11X)( I,845,000jo_3.2n0.n00 platelets/uLlJiad-aiLinhibitorveffect on osteoblast activity when compared wjth lowerconcentrations. In a study on alveolar bone cells, Choi etal.56 concluded -that. .the. high, concentration of plateletsused may have resulted in adverse effects on bonegrowth.

Platelet Count

A single individual's platelet count can vary con-siderably on different days.18 There is also a- signifi-cant variation in platelet count-between individuals.For example, the normal platelet count varies between150000 and 350,000 platejels/j^L. An individual witha low normal count receiving PRP with a concentra-tion of 1 million platelets//xL would see an approxi-mate 6.5 X increase. Arnndividual with a high normalcount receiving PRP with a concentration of 1 million

would seean approximate 3X increase.Variations in an inch victual's baseline platelet countlead to inconsistency in quantifying a "fold" increase,making PRP products different between both individ-uals and treatments, even when identical protocols areused. For this reason, documenting both the absolute

number of platelets per microliter contained in thePP^_ preparation., and Jhe. individual's own plateletcount on the day of treatment is important in compar-ing effectiveness.- • - .. . ......

Centrifugation force, duration, and frequency arealso important elements that may result in varyingplatelet concentrations and alteration of platelet mor-phology.57 Jo et al.58 determined optimum PRP gelformation by varying time and gravitational forcesduring centrifugation. The optimal conditions werefound to be 900g for 5 minutes and 1,500# for 15minutes for the separating centrifugation step and thecondensing centrifugation step, respectively. In addi-tion, Barrett and Erredge59 found that the number ofcentrifugations varied platelet capture significantly.They determined that a single centrifugation spin pro-duced 1,254,000 platelets//xL whereas a double spinproduced 2,017,000 platelets//uL.

The process for measuring platelet count may con-tribute to variation as well. Most hematology analyzersystems are designed to operate in ranges found withinwhole blood, and PRP may exceed the upper limit ofthe linear range of platelets that can be counted. Inaddition, adequate resuspension of the PRP and propersample preparation are required for accurate plateletcounts. Platelet clumping or lack of even distributionmay result in inaccuracies.1 (

Woodell-May et al.1 determined the average plateletcount to be significantly less when samples were mea-sured immediately after preparation of the PRP thanwhen samples were resuspended on a rocker (P < .05).This study suggests that for accurate platelet counts to beachieved, the_entire PRP sample must be remove^ andallowed to sit on a rocker for ajjeast 5 minutes beforecounting. Furthermore, this study recommends usingmanual mode in the hematology analyzer because auto-matic counting .modes are. more Jikely to allow the sam- 'pie to settle, reducing the absolute platelet count.32

Leukocyte Content

The effect of highly concentrated WBCs containedwithin PRP preparations60 has been hotly debated. PRPsystems that use a buffy coat contain an increased concen-tration of WBCs above baseline levels, whereas plasma-based methods do not. Although normal levels of WBCshave a positive immunomodulatory effect, heightenedlevels in some PRP preparations may have a deleteriousimpact. Literature suggests that excessive leukocytes,specifically neutrophils, may be contributing to theseundesired results.zrn~Ho\*t'everrth'5"efficaciy

treatments still remains unclear and may be

1002 J. M. BELONG E

dependent on indication. PRP used to treat opewounds and prevent infection may rcauirejjupraiigf-mal WBC levelg,61-64 whereas^PRP used to minimize

WBCcontent should always be documented in any classifi-cation system.

UNDERSTANDING DELIVERY METHOD

Activation Methods

Platelets can be activated endogenously or throughthe addition of an exogenous clotting factor to anycommercially available system. Each type of activatormay produce varying effects and significantly influ-ence growth factor kinetics. Accurately documentingthe deliver}' method and activation scheme used isanother key to a successful classification system.

Exogenous: Exogenous activation results in rapidcoagulation of platelets and quick clot formation. Forthis reason, clots formed in this manner are best ap-plied manually to the tissues, rather than administeredby injection. They often can be sutured to repairs.Proposed benefits of a preformed clot include theability to more accurately localize growth factor re-lease, as well as decreased diffusion when used intra-articularly. Advocates of preclotted PRP also theorizea more sustained growth factor release because growthfactors are thought to elute from the clot slowly overthe span of several days. The effect of exposure of theclot to synovial fluid has not been well documented,and it is possible that the clot is quickly dissolved inthe joint.66-67

Endogenous: The addition of external clotting fac-tors to PRP may not be needed to significantly activateplatelets. Not only will tissue collagen cause activa-tion of platelets but simple_agitation jjf p]atelets? suchas centrifugation, as well as needle-induced bleedingduring PRP injection, may provide the appropriateendogenous clotting factors needed for activation. En-dogenous activation has the potential for slower ag-gregation of platelets and release of growth factors byallowing collagen within the tissue to operate as theactivator providing a natural release pattern.68 Clotformation occurring after injection provides the ben-efit of administration through a needle and may allowa more precise delivery to, and within, the targettissue.

Platelet Activators

Thrombin: Thrombin causes rapid aggregation ofplatelets. Rapid activation may lead to excessive con-

densing of the fibrin matrix and significant retraction.of cloTs, which m^nilTiriierior with respect to cellmigration and growth factor enmeshment when com-pared with less condensed physiological activa-tion.69'72 A rapid activation may also lead to a de-crease in the total amount of growth factors availableat the tissue site over time.short half-life minutes d-will^&^ade-beforeadditional tissue receptors become available if they arenot immediately .used upon release from a platelet.68-73

Additional potential negative effects include an immune-

tion against bovine-derived thrombin.68

CatctmTTT^hloride: Calcium chloride has beenadded exogenously to PRP preparation in lieu of bo-vine thrombin and may result in the formation of a lesscondensed fibrin matrix. The fibrin matrix may pro-vide a trapping mechanism for platelets, resulting insmaller amounts of thrombin formation endogenously,allowing a slower release of growth .factors over a7-day period, which may enhance cell migration andhealing .7^-74;?? Injections. containing-cakJAjm-Gbloadehave a low pH amTcause significantLpaJn and a burn-ing . sensation .to the . patient.

Calcium Chloride Plus Thrombin: Calcium chlo-ride is a citrate inhibitor and allows the plasma tocoa^uiaLe^_an.dJ±LrQnibin causes fibrin to polymerizeinto, an insoluble gel: platelets then degranulate andrelease growth factors.57 When calcium chloride andthrombin are combined with PRP a gel or _ .scaffoldmatrix is produceo7~TEs^^nmy^)ffer_the benefit of a

Type I Collagen: Endogenous type I collagen hasbeen found to be equally effective as thrombin inactivating platelets and stimulating the release ofgrowth factors. In an in vitro study of PRP fromhuman donors, clotting was performed with type Icollagen or bovine thrombin. Type I collagen resultedin similar release of PDGF and VEGF but a moreextended and overall greater release of TGF-/3 thanthrombin. Clots formed by use of type I collagen alsoexhibited far less retraction than those formed withbovine thrombin. In addition, both type I collagen andbovine thrombin stimulated similar release of PDGF andVEGF between days 1 and 10, whereas thrombin re-sulted in a greater release of TGF-/3 during days 1 to 5 .7S

Delivery Technique

The technique used during delivery of PRP is an-other fundamental variable that should be understoodand addressed. Individual tissues may have ideal an-

PLATELET-RICH PLASMA CLASSIFICATION 1003

TABLE 2. Types ofPRP Delivery

PRP Platform Specific Activator/Modality'

Liquid injection

Spray

Gel

Clot (fibrin matrix)

EndogenousCaCI2

EndogenousCaCl2 + thrombinThrombinCaCl2 + thrombinThrombinCaCl2 + centrifugationCaCl2 + thrombinThrombin

Abbreviation: CaCU. calcium chloride.

atomic locations for delivery of PRP. For example,PRP injection into the osseotendinous, midsubstance,or myotendinous zone of a tendon may produce vary-ing results.46 An in vivo rabbit model study deter-mined the effect of PRP on insulin-like growth factor(IGF) 1 expression in the epitenon and endotenon ofrabbit Achilles tendons. At-week 4, histologic analysisshowed superior expression of IGF-1 in the epitenonof the PRP group versus the saline solution group,which produced superior IGF-1 levels in the endote-non (P < .0001).77

The PRP deliver}' platform (liquid, spray, gel, orclot) should be selected based on procedure type (open

y artriroscopic) and whether slow or fast activation ofplatelets is desired (Table 2).

PAW CLASSIFICATION SYSTEM

With all of the previous information being takeninto consideration, the PAW classification system ofPRP is based on 3 components: (1) the absolute num-ber of Platelets, (2) the manner in which plateletActivation occurs, and (3) the presence or absence ofWhite cells. By analyzing these 3 variables, we are ableto accurately compare publications (Tables 3 and 4).

Platelets and White Cells

The first part of the classification system identifiesthe specific cellular components of platelets and whitecells contained within the PRP preparation and shouldbe documented as follows (Fig 1). Platelet concentra-tion should be measured in platelets per microliter andcategorized as follows: PI, less than or equal to baselinelevels; P2, greater than baseline levels to 750,000 plate-lets/juL; P3, greater than 750,000 to 1,250,000 platelets/juL; and P4, greater than 1,250,000 platelets/pL.

Total WBC content is identified as either above (A)or below/equal to (B) baseline levels. Systems desig-nated with an "A" are buffy-coat systems, whereasplasma-based systems fall under "B." Because the

TABLE 3. PAW Classification of Plasma-Based Systems and Buffy Coat-Based Systems

WBCs PAW Classification

Device NamePlatelet Activation Total WBC Neutrophil

Concentration Method* Content Content Endogenous Exogenous References

Plasma-based systemsArthrex/ACPCascade/MTF FibrinetBTI/PRGF

Buffy coat-based systemsfBiomet GPS II/III

Harvest SmartPReP 2/DePuySymphony II

Arteriocyte/MedtronicMagellan

Emcyte GenesisCS/Exactech Accelerate

P2P2P2

P2P3P4P2P3P4P2P3P4P4

* B /3 P2-B0* B /3 P2-Bj3'* B p P2-B/3

* A a P2-AaP3-AaP4-Aa

* A a P2-AaP3-Aa:P4-Aa

* A a P2-A«P3-AaP4-Ao;

* A a P4-Aa

P2-X-B/3P2-X-B/3P2-X-B/3

P2-x-AaP3-x-AaP4-x-AaP2-x-Aa

P3-x-AaP4-x-AaP2-x-AaP3-x-AaP4-x-AaP4-x-Aa

2214, 23-2526-2S

29-33

24, 32-35

14, 33, 36, 37

38-40

""Ultimately, researchers can choose to activate platelets endogenously or through the addition of an exogenous clotting factor to-anycommercially available system.

|Buffy coat-based systems typically produce highly variable platelet concentrations.

TABLE 4. PAW Classification of Clinical Studies*

Condition Treated

Medial/lateralepicondylitis

Achillestendinopflthy/rupture

Patellartendinopathy

Authors

Hechtman et al.7S

{Orthopedics,2011)

Thanasas ct al 79

(Am J SportsAM/, 2011)

Peerbooms el a I.,80

1-yr follow-up(Am J SportsMed, 2010)

Gosens et al.,31 2-yrfollow-up (Am JSports Med,2011}

Mishra andPavelko81 (Am JSports Med,2006)

de Vosetal.*6 (BrJSpans Med,2011)

de Jnngc ct al.,83

1-yr follow-up(Am J SportsMed, 2011)

Schepull et al «(Am J SporlsAM;, 201 1)

Filardo ct al.85

(Orthopedics,2010)

Sanchez ct al.38

(Am J SportsMed. 2007)

Filardo ct al.86 (In!.Onhop, 2010}

EvidenceLevel Study Type

IV Case series, prospectivestudy

1 Randomized controlledsingle-blind trial

1 Randomized controlledStudy

I Randomized controlledStudy

II Prospectivecomparative study

I Double-blindrandomized placebo-controlled study

I Double-blindrandomized placebo-control led study

II Randomized controlledsingle-blind study

IV Case study

III Case- control,descriptivelaboratory study

11 Prospectivecomparative study

No. of Patients

PRP group previouslyunresponsive to nonsurgicaltreatment (n = 31)

PRP group (n = 14) vautologous whole bloodgroup (n = 14)

PRP group (n = 51) vcortices leroid group(n = 49)

PRP group (n = 51) i-i corti co steroid group

(n = 49)

PRP group (n = 15) vbupivacainc group (n = 5)

PRP group (n = 27) vplacebo-saline solutioninjection (n = 27)

PRP group (n = 27) vplacebo-saline solutioninjection (n — 27)

PRP group (n = 16) v controlgroup (n = 14)

PRP group (11= 1}

PRGF athlete group (n = 6)

PRP group with 3 injections(n = 15) v exercise-onlygroup (n = 16)

PRP Outcome

(+) Improved pain and functionscores, thus avoiding surgery

(+) Effective for chronic lateralelbow epicondylilis

(+) Reduced pain, increasedfunction

(•I-) Reduced pain, increasedfunction

(+) Reduced pain in chronicsevere tendinosis in patients inwhom nonoperative treatmenthas failed

(Neutral) PRP injection did notresult in greater improvementin pain and activity overplacebo injection

(Neutral) PRP injection did notresult in greater improvementin pain and activity overplacebo injection

(-} PRP not useful for treatmentof Achilles tendon ruptures;lower Achilles tendon totalrupture score, thus suggestingdetrimental effect

(+) Fast tissue repair and returnto full function

(•f) Earlier ROM recovery andreturn to activity

(+) PRP has potential to achievesatisfactory clinical outcome.even in difficult cases with

System

Cascade MTF

Biomct GPSIII

Biomel

Biomct

Biomct GPS

Biomel GPSIII

Biomel GPSIII

NA

NA

BTI/PRGF

NA

PlaleletsVL

NA

1,292.5005.5 X

NA

NA

3,310,0005.39X

NA

NA

3,673 ± 1,051 x10"

17X

6.5 X I06

6.1X ± 1.6

NA

6.5 X 10s

6.1X ± 1.6

ActivationMethod

Exogenous CaClj

Endogenous typeI collagen

Endogenous typeI collagen

Endogenous typeI collagen

Endogenous type1 collagen

Endogenous typeI collagen

Endogenous type1 collagen

Endogenous typeI collagen

Exogenous CaG2

Exogenous CaCl2

Exogenous CaCl2

WBCs

Below

Above

Above

Above

Above

Above

Above

NA

NA

Below

NA

PAW

NA-x-B/J

P4-Aa

NA-Aa

NA-Art

P4-NA-A«

NA-Aor

NA-An

P4-NA

P4-X-NA

NA-x-B/3

P4-X-NA

OO-P-

st=-fSj

bt~-<p-SQhi

t̂^t— <

Kon et al.sj (Injury,2009)

Rotator cuff Jo et al.8S (/1m Jreconstruction Sports Med,

2011)

Randelli et al.89 (JShoulder Elbow

IV Prospective study PRP group {n = 20) evaluatedat 6 mo :

II Prospective cohon PRP group (n = 19) v controlstudy group (n = 23) -

I Prospective randomized PRP augmentation groupcontrolled study, (n = 26) v control group2-yr follow-up (n = 27)

chronic refractory tcndinopathyafter previous classicaltreatments have failed

(4-) Aided regeneration of tissuewhich otherwise has lowhealing potential

(Neutral) Did not clearly showaccelerated recovery clinicallyor anatomically

(+) However, improvement ininternal rotation

(+) Reduced pain in firstpost opera live months; long-term results of subgroups ofgrade 1 and 2 tears suggestthat PRP positively affectedcuff rotator healing

NA

COBE spectraLRS Turbo(Lake wood,CO)

6 X I0r'fix

1,400 X I03

(adjusted viasaline solution to1,000 X 103)

Exogenous CaCl2 NA 1'4-x-NA

Biomet GPS II NA

ExogenousCalciumGluconnle

Exogenous CaCl2

4- thrombin

NA P3-X-NA

Above NA-x-Aa

PLATELET-RICH PLASMA CLASSIFICATION 1005

^ ^ U os- fl 6= # L. CL

.^.25 ™ e S P S^ ~ •— ^-« -— E ^- ?

C 3,s c*H tQ

61) "g"

t: 3U C CT'^ C CU

•i

PRP "PAW" Classification Systemooo\S

ACTIVATION

METHOD

exogenous

M/HITE BLOOD CELLS

Total WBC's NEUTROPHILS

Abovebaseline

Below or-tobaseline

abovebaseline

pelow or=tobaseline

B

b

example: P 2 - B P or P2 - B

example: P 3 - x - A a

FIGURE 1. PRP PAW classification system.

PLATELET-RICH PLASMA CLASSIFICATION 1007

inclusion or exclusion of neutrophils willbecome animp ortant variableLa_gubcategory for neujroghtl counthag been createdlbr^sYstems that concentrate WBCs.If neutrophils are included in the buffy coat then_a(abp_ye) is added. If neutrophils are filtered out,J_hen /3fbelov.0 is ad4&l Thf»Tftfnr&-hiifly=f:nat systems ..willhave a designation of either Aa or A/3 in our system.

For example, a PRP preparation consisting oF900,000 platelets//nL with a total WBC and neutrophilcontent above baseline levels will be documented as

Activation Method

Ultimately, researchers can choose to activate plate-lets endogenously or through the addition of an exog-enous clotting factor to any commercially availablesystem. Endogenous activation is not given a desig-nation. However, if an exogenous external activator isused, it is documented with an x. Combining thepreviously described PRP preparation with this acti-vation method will provide the complete classifica-tion: either P3-Aa for endogenous activation or P3-x-Aa for exogenous activation.

CONCLUSIONS

PRP continues to occupy both orthopaedic literatureand the lay press, and more funding is being dedicatedto unraveling its mysteries; a simple method for com-paring published data based on the content of PRPneeds to be established. Our system offers a simple,effective method for quickly documenting the cellularcomponents and activation method used. The acronymPAW serves as a pneumonic for Platelets, Activation,and White cells, and the subcategories are thought-fully organized to enhance recall. Using a classifica-tion system will speed the process of identifying theoptimal PRP preparation for each indication and allowother investigators to replicate published data or per-form meta-analyses.

Acknowledgment: The following individuals are ac-knowledged for their substantial contribution in the devel-opment of the classification system: Bryan T. Hanypsiak,M.D., David O. Shepard, M.B.A., C.T.B.S., and Brandon L.Roller, M.D. All are employees of Arthrex, Naples, Florida.

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Systematic Review

Open Capsular Shift and Arthroscopic Capsular Plication forTreatment of Multidirectional Instability

Mark E. Jacobson, M.D., Michael Riggenbach, MX)., Adam N. Wooldridge, B.A., B.S., andJulie Y. Bishop, M.D.

Purpose: To compare the results of open inferior capsular shift with arthroscopic capsular plicationfor multidirectional instability in patients without a Bankart lesion. We hypothesized that there is nodifference with regard to the specific clinical outcomes evaluated, including recurrent instability,range of motion, return to sport, and complications. Methods: We conducted a comprehensiveliterature search. Databases searched included PubMed from 1966 to 2010, the Cochrane Databaseof Systematic Reviews and Controlled Trials, CINAHL (Cumulative Index to Nursing and AlliedHealth Literature) from 1982 to 2010, and SPORTDiscus from 1975 to 2010. Limits included Englishlanguage, human subjects, and title. Results: We found 7 articles with a total of 197 patients (219shoulders) that met our inclusion criteria. The data did not clearly show open treatment to be superiorto,arthroscopic treatment. No study reported a consistent loss of greater than 40° of external rotation.No technique showed significantly less external rotation loss over the other. Whereas there was aslight trend toward increased return to sport for patients treated arthroscopic ally, no clear conclusioncan be drawn given the variability of reporting in the reviewed studies. Analysis of complicationsshows that both procedures are reliably safe with minimal complications. Conclusions: When one isevaluating patients with traumatic or atraumatic onset of shoulder instability in 2 directions and nostructural lesions, arthroscopic capsular plication yields comparable results to open capsular shiftwith regard to recurrent instability, return to sport, loss of external rotation, and overall complica-tions. Level of Evidence: Level IV, systematic review of Level IV studies.

In 1980, Neer and Foster1 coined the term "mul-tidirectional instability" (MDI) and proposed

specific surgical treatment to patients in whom con-servative management has failed. In this classicarticle they report preliminary results of the inferiorcapsular shift as a means to address the patulous

From the Division of Shoulder Surgery, Department of Ortho-paedics, The Ohio State University, Columbus, Ohio, U.S.A.

The authors report that they have no conflicts of interest in theauthorship and publication of this article.

Received September 30, 2011; accepted December 6, 20] 1.Address correspondence to Julie Y. Bishop, M.D., Department of

Orthopaedics, The Ohio State University Medical Center, 2050Kenny Kd. Ste 3300, Columbus, OH 43221, U.S.A. E-mail: Julie, bishop @osumc. edu

© 2012 by the Arthroscopy Association of North America0749-8063/1162 7/$36.00doi:10.1016/j.arthro.201L12,006

inferior capsule that they believed to be the respon-sible pathology. Although open inferior capsularshift remains the standard in surgical treatment ofMDI, multiple alternative procedures have been de-veloped. In 1993, Duncan and Savoie2 first reportedpreliminary results of arthroscopic capsular plica-tion.

In all patients presenting with MDI, a regimentedcourse of physical therapy directed at strengtheningof scapular stabilizers, the rotator cuff, and thedeltoid is warranted.1*3-4 Burkhead and Rockwood4

reported good or excellent results in 88% of patientswith atraumatic instability treated with an exerciseprogram; however, more recent results have beenless encouraging, at 30% to 61%.3'5 If these recentreports more adequately represent our current pa-tient population and its expectations, it is reason-

1010 Arthroscopy: The Journal of Arthroscopic and Related Surgery, Vol 28, No 7 (July), 2012: pp 1010-1017