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1. Autologous Conditioned Plasma in the Treatment of Sports Injuries Ariko Iso, MA, ATC
Pittsburgh Steelers
3. Biologics in Sports Medicine? Platelet rich therapies present significant opportunities as well as significant questions about appropriate clinical applications for this developing therapy & the legality of its use in professional sports ( OK in NFL & NCAA) WADA a different story
A clear understanding of the repair response & the variables that may affect the effectiveness of ACP therapy is necessary to make informed clinical judgments on its use
4. Platelet Rich Therapy Introduction Platelet rich therapies contain “HEALING” (growth) factors that accelerate the biologic processes necessary for repair of soft tissues following acute traumatic & overuse injuries
Methods to deliver high doses of GF to injured tissue
Platelet rich plasma (PRP)
Autologous Condition Plasma (ACP)
Both have in common a reliance on growth factor release from platelets
5. Platelet Rich Therapy Introduction
Most musculoskeletal injuries involve anatomic areas with minimal blood flow & low cell turnover rate
Joint spaces, ligaments & cartilage have a naturally limited blood supply
Muscle & tendons commonly experience decreased local blood flow following injury
This imbalance of growth factor supply & demand hinders the regenerative process
6. Ortho Biologics
Platelet rich therapies allow for an opportunity to utilize the body’s own Healing (growth) Factors to improve the quality & speed of recovery from an injury.
7. What was the turning point ? Hx: January 18, 2009
Pro Bowl wide receiver sustained a valgus stress to his right knee during the AFC Championship game
Diagnosis
Grade 2 MCL Sprain
8. Case #1 MRI Findings MRI performed 1/20/09
Medial retinacular & grade II MCL tear
Reported medial knee discomfort, FAROM, excellent quad sets
Treatment: ACP #1
Game Ready
Grade II MCL Tear
9. Case #1 1/21/09
Reported no changes from yesterday
Fitted for hinge brace
Treatment: US 3MHz 20%
Bike
SLR #5
Game Ready
Hybresis
10. Case #1 1/23/09
Noted some improvement
FAROM, Excellent Quad sets, decreased discomfort and echymosis
Treatment: US 3MHz 50%
Eliptical, Stair Master
SLR #7.5
Game Ready
Hybresis
11. Case #1 1/26/09
ACP #2
Travel to Tampa
Continue treatment and rehab
Participate Super Bowl Functions
1/28/09
Noted improvement
Denies pain or dysfunction
12. Case #1 2/01/09
Pt denied knee pain
Pt was cleared for practice at 10 days
Pt returned to play 14 days after initial injury
Tells Media in front of a national audience he had ACP which allowed him to play
13. Healing Cascade Made Easy
14. What Are Platelets? Fragments of cells originating from bone marrow that live between 5-9 days
They contain growth factors & other molecules to control wound healing and homeostasis (clotting)
When activated they release growth factors when they come in contact with damaged tissue (collagen) Platelet Activation
15. How do GF work ?
16. Basic Biology of GFs GF are proteins secreted by many different body tissues: connective tissue fibroblasts FGF, stem cells G-CSF, white cells cytokines, platelets PDGF VEGF, TGF, EGF, FGF also solid organs liver IGF1
All have a short half life with rapid disappearance
Their effects are confined to the site of delivery
GF are stored in the alpha granules of the platelets
Platelets are the 1st to arrive at the injury site and they mediate the healing response
This is why platelets are used as the delivery tool for GFs
17. What is in ACP ? Platelet derived
Activation leads to a-granule release
a-granules contain:
IGF-1
TGF-ß1
VEGF
PDGF
bFGF
EGF
Plasma derived-HGF,IGF-1
Minimal WBCs
18. Important Growth Factors
19. What Are Growth Factors? Proteins found in the body that assist in the healing and formation of hard and soft tissues.
Functions:
Promote cell migration/proliferation
Promote collagen formation
Stimulate angiogenesis
Modulate matrix formation
20. Growth Factors & Soft Tissue Healing: the literature
Kurtz CA et al IGF-1 accelerates functional recovery from Achilles tendon injury in a rat model. Am J Sports Med 1999; 27(3): 363-9.
25 µg IGF-1 in methylcellulose gel carrier to transected rat Achilles tendons
Restored function and reduced inflammation from 24 hours up to 15 days
21. Growth Factors & Soft Tissue Healing
Hildebrand KA et al. The Effects of PDGF-BB on Healing of the Rabbit MCL. Am J Sports Med 1998; 26(4): 549-54.
Applied low and high doses of PDGF in fibrin sealant to ruptured rabbit MCLs, sham-operated knees in same animals as controls
After 6 weeks, higher ultimate load of femur-MCL-tibia construct for high dose PDGF compared to low dose and fibrin sealant alone
22. Growth Factors & Soft Tissue Healing
PRP applied to ruptured Achilles tendons of a professional basketball & professional football players in conjunction with operative repair led to earlier return to play in 14 weeks
Sanchez et al
23. Growth Factors & Soft Tissue Healing PRP in the treatment of chronic elbow tendinosis resulted in:
60% pain improvement vs 16% in controls at 8 wks
2 year follow-up, PRP treated patients showed 93% improvement in pain, & 94% return to sport/work
Mishra et al Am J Sports Med 2006;34
24. Growth Factors & Soft Tissue Healing In ACP treated human muscle strain injury, there was complete versus partial regression of subjectively assessed MRI findings in ACP treated patients
ACP treated patients RTS at a mean of 16.6 vs. 22.3 days in controls
Wright-Carpenter et al, Int J Sports Med 2004 Wright-Carpenter et. al. reported:Wright-Carpenter et. al. reported:
25. Biologics in Sports Medicine Has primarily focused on improving platelet/plasma delivery to areas of injury
Practical challenges to use of biologics in sports medicine applications
Cost containment
Added time to the procedure
Regulatory control
Cost and time for development
Quantifying results
26. Lets look at the issues
Practical challenges to use of biologics in sports medicine applications
Cost containment - 150 dollars/syringe vs 600-800 PRP
Added time to the procedure - 10 mins vs. 20 mins PRP
Regulatory control - FDA approved for surgical sites
Cost & time for development - done
Quantifying results – many animal studies, human early but good with many centers now involved
27. What are our options
28. Platelet Rich Plasma Methodology first developed by Marx
PRP
The therapeutic outcome of a technique involving centrifugation of autologous blood which allows the extraction of plasma which contains a high concentration of platelets
Additives
Requires addition of an anticoagulant – Dextrose A, in order to prevent platelet activation prior to its use.
Platelets are activated at the time of injection with the addition of Ca and Thrombin.
29. PRP – How Does it Work? 2 Centrifugations
1st separates RBCs/WBCs from Platelets/Plasma
2nd separates Platelet Rich Plasma (PRP) from Platelet Poor Plasma (PPP)
Still has White cells
30. Platelet Rich Plasma PRP extract injected into damaged tissue
Platelets begin secretion of growth factors within 10 min, 95% growth factors released within 1 hour
Platelets are viable for 7 days and continue release of growth factors into tissue
31. Our Answer is ACP by Arthrex Autologous Conditioned Plasma
An easy to use double syringe system to concentrate platelets using a centrifuge
We want the yellow plasma layer on top, not the red and white blood cells on the bottom
Increased concentration of platelets & growth factors in the yellow plasma layer can alter the healing process QuestionQuestion
32. What Does ACP Look Like?
33. ACP VS PRP
34. ACP vs PRP ACP advantages include:
Easy to use system
PRP system often require rep-support due to its complicated process
Quick procedure time
Double centrifugation process for PRP more than doubles procedure time
Inexpensive
PRP devices & syringes cost >2-6x as much as ACP equivalents
Minimal required blood volume
PRP systems require 60-120cc blood, ACP requires 10cc
Has no additives
Reduced level of RBC and WBCs
Similar GF concentration to other systems
35. HOW ACP is MADE
36. Potential Risks of Using Growth Factors in Sports Medicine
37. Potential Complications Fibrosis
TGF-B1 regulates balance between regeneration & fibrosis
Infection same as any injection
Carcinogenesis
Growth factors act on cell surface receptors, do not enter the cell, and do not cause DNA mutation
Systemic effect on serum growth factor levels IGF-1 (HGH) too short a half life, isoformIGF-1Ea in PRP not responsible for muscle hypertrophy(IGF-1Ec &MGF), doses of IGF-1 are subtherapeutic in terms of anabolic action by a factor of 500 ( 300 ng vs. 160 ug) WADA does not get this YET
Question on last paragraphQuestion on last paragraph
38. Therapy vs Doping:IGF-1 content of PRP
The unbound IGF-1 has too short a half-life to be able to exert systemic effects (10 min vs 16 hours)
Isoform IGF-1Ea found in PRP is not the isoform principally responsible for skeletal muscle hypertrophy (IGF-1EC/MGF)
Doses of IGF-1 in PRP are sub-therapeutic in terms of producing systemic anabolic actions by a factor of 500 (300ng vs 160 ug)
39. How can biologics treat these injuries?
40. Clinical Applications for Platelet Rich Therapies
41. Clinical Applications for Platelet Rich Therapies
42. Evaluated Methods of Concentrating Platelets Arthrex Double-Syringe® Autologous Conditioned Plasma (ACP) 10 cc blood/yield = 3cc product
Biomet GPS® II Platelet Concentrate System
27cc blood/yield = 3cc product
Musculoskeletal Transplant Foundation CASCADE® Autologous Platelet System
9cc blood/yield = 2cc product
Platelet Rich Plasma (PRP) – Literature Based Platelet Concentration Method
10cc blood/yield = 1.5 cc product
43. Platelet Concentrations
45. Why with a 4 fold increase in platelets is there no difference in tendon growth?
46. Platelet to White Blood Cell Ratio
47. WHY ? It is all about the ratio of Platelets to WBCs in the solution
2000 (platelets) to 1 (WBC) appears to be the correct ratio
What is the ratio in ACP?
2000 to 1
That is why even though you have more platelets in other preparations you do not get an additive effect on cell proliferation
48. Effects of Leukocytes (WBC) on PRP Effectiveness Contaminating WBCs contribute to the overall GF content of PRP.2,3
WBCs are believed to be contaminants in PRP.2
The # of WBCs in PRP critically effects the production of destructive lysosomes & cytokines in PRP.1
Little is known about in vivo effects of contaminating WBCs in PRP & their specific cytokine & GF content.2
49. HOW WE USE ACP Performed in Team Physician’s Office
Draw 10 ml of blood without ACD-A (less pain with injection)
Use 3-5 ml of platelet extract for injection
Direct injection at site of injury (blind)
Digital MRIs, CT guided or Ultrasound for localization
Typically 2 to 3 injections between 5-7 days apart
50. STEELERS ACP USE
51. Case Example # 2 Date of Injury 8/22/09
History
23 year old, professional NFL quarterback
Right hand dominant
Mechanism of Injury: tackled & landed on right shoulder
52. Case #2 Diagnostic Studies
(8/23/09)
Demonstrate Grade III AC separation
Plan
Ice applied to shoulder
Pt placed into a sling for comfort
53. Case #2 8/24
54. Case # 2 8/25/09
50 hours after initial injury
Athlete received 1st of 3 ACP Injections to right AC joint
55. Case #2 8/25/09
Training Room Clinic Hour
He is doing well with minimum discomfort
Long discussion regarding Dos and Don’ts
With his position and the degree of sprain, although he is exceptionally doing well at this time, we will progress slowly. Focus on passive ROM rehab
56. Case # 2 Patient returns 1 week later and reports no pain with shoulder ROM
Examination
Mild tenderness at AC joint
No pain with shoulder ROM
Plan
Patient given 2nd ACP injection
Patient slowly progressed to throwing
57. Case # 2
58. Case Example # 3 History
27 year old NFL running back c/o pain & a “pop” sensation in hamstring
Unable to return to play due to pain & difficulty running
Date of Injury: 8/6/09
Examination
Non antalgic gait
(+) pain with resistive hamstring strength @ 45 degrees
Good knee ROM
(-) Plank Test
59. Case #3 Diagnostic Studies
Grade II hamstring strain
Plan
Athlete given ACP injection under sterile conditions to hamstring 24hours after injury
60. Case # 3 8/13/09
Athlete returns for second ACP injection
Reports decrease in pain
Examination
+ pain with hamstring manual muscle testing @ 45 degrees
61. Case # 3 Athlete reports he is improving but not yet at 100%
Examination
No pain at 10, 45 or 90 degrees
(-) Plank test
Plan
Athlete given 3rd ACP injection under sterile conditions 8/20/09)
62. Case # 3 Summary
Date of Injury: 8/6/09
Athlete reports significant improvement in hamstring strength 20 days after injury
Examination
5/5 hamstring strength
No pain at 10, 45, or 90 degrees
Plan
Athlete allowed to return to practice/games
63. Case Example # 4 History
Date of Injury: 8/05/09
26 years old NFL WR experienced “grab” while he was accelerating out of a break running pass route
Examination
4/5 hamstring strength
Drag 7/10
No deformity, mass edema or echymosis
MMT: deferred due to pain
64. Case # 4 8/6 09 MRI was performed
Biceps Femoral middle distal 1/3 Grade II strain
First ACP treatment
Rest and Ice
65. Case # 4 8/7/09
Noted pain with normal daily activities
No obvious edema, echymosis
Decreased PROM by 20%
MMT 5-/5 at knee flexion 90 deg.
4/5 at knee flexion 30 deg.
Treatment: Bike
Standing ham curl
Bridging
Walk forward and backward on the field
Game Ready
66. Case # 4 8/11/09
Second ACP injection
Rest and ice, resume rehab on 8/12
8/12 09
PROM hip flexion decreased by 10-15 %
MMT: 5/5 90 deg. hip flexion, 4/5 4/5 hip flexion
Bike
Lower body lifting
Striders and agility drills during practice
67. Case # 4 8/15/09
Participate practice (individual portion)
Denies soreness from previous day rehab
Continue lift and treatment
8/16/09
Participate full practice as pain allows
8/27/09
Injury closed
68. SUMMARY Ageing: the bodies repair system slows
Early studies show ACP can alter it
Basically, kick start the healing process
Follows KISS Principle
This is the evolution from surgical to biologic repair
Amount, frequency & quantity of growth factors are being investigated
69. Conclusion
The use of ACP promises to become a powerful therapeutic modality for use in muscle, tendon, bone & ligament injury
This technology is still in its infancy with respect to musculoskeletal injuries & further studies to characterize its potential role on improving healing are now ongoing
70. Thank You