Presentation pdf - Stony Brook University School of Medicine

Marco Palmieri, DO
Assistant Professor
Department of Anesthesiology
Stony Brook University Medical Center
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Composition of Blood
The Healing Process: A Review
What is Platelet Rich Plasma (PRP)?
Current Literature & Clinical Applications of
PRP Therapy
Facet Joint Arthropathy: Current Standard of
Care
Q&A
References
•  Cells:
–  Erythrocytes (4.2mil to 6.1mil/mL)1
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O2 Transport
–  Leukocytes (4k to 11k/mL) 2
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Immune Response
–  Thrombocytes (200k to 500k/mL) 2
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Hemostasis and coagulation
Proteomic function* (>800 proteins)
•  Plasma:
–  Approximately 55% of whole blood is
plasma
–  92% H2O & 8% proteins
Courtesy of http://en.wikipedia.org/wiki/File:Blut-EDTA.jpg
•  The necessary stages of healing:3
–  Inflammatory
–  Proliferative
–  Maturation and/or Remodeling
•  Inflammatory phase lasts for days to one week
•  Involves hemostasis and recruitment of inflammatory mediators
•  Growth factors
•  Transforming growth factors (TGF- β, TGF-α)
•  Basic fibroblast growth factor (bFGF)
•  Platelet derived growth factor (PDGF)
•  Vascular endothelial growth factor (VEGF)
•  Switch from pro-inflammatory to pro-healing activity may determine
effective repair versus failure of repair3
•  A common characteristic of impaired healing is persistent
inflammatory response (prolonged elevation of pro-inflammatory
cytokines and macrophages) 3
•  Typically follows for the next days to two weeks
•  Cell migration, proliferation and differentiation of progenitor cells
occurs in response to various cytokines and growth factors present
•  Progenitor cells of bone, cartilage, muscle, nerve sheath, and
connective tissue
•  Formation of extracellular matrix with angiogenesis, granulation,
contraction, and epithelialization
•  This phase ensues and can last for weeks to over one year
•  Balance between synthesis, deposition, and degradation during this
phase
•  Most dramatic changes occur in the overall type, amount, and
organization of the collagen fibers  results in increased tensile
strength of the tissue3
The physiology of healing of the chronic wound.
From emedicine.com4
•  Platelet Rich Plasma Therapy (PRP)
•  Regenerative Biomedicine (ie. PRP, MSC, prolotherapy, etc.)
–  Current applications for PRP by several medical disciplines,
including plastic surgery, OMFS, ENT, orthopedics, and pain
specialists
–  Prepared by centrifuging autologous, anti-coagulated whole blood
–  Amount of blood withdrawn varies according to application
(20-60mL)
–  Separates into the following:
–  1) plasma layer (platelet poor layer)
–  2) platelets and WBC (buffy coat)
–  3) red blood cells
•  Centrifugation separates PRP aliquot:
–  Platelet-Poor Plasma
•  Platelets < 50,000 per µl:
–  Buffy Coat
•  less than 1% of the total volume of the
blood sample
•  contains most of the white blood cells and
platelets
–  Erythrocytes
•  PRP concentrates platelets 5 times:
–  ~ 200,000 per µl → 1,000,000 per µl
Courtesy of http://doctorricklehman.com/wp-content/uploads/2010/03/current-concepts-and-application-in-sports-medicine.jpg
Courtesy of Harvest Technologies
Courtesy of Harvest Technologies
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Many variations among various commercial PRP preparations
No clinical evidence to support one versus the other
Much variability exists including:
  Inclusion of WBC’s
  Activation with thrombin or calcium chloride
  Concentration of platelets
  Incubation of PRP product (Orthokine)
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PRP is re-introduced to the area of injury
Introduce a supra-physiologic amount of autologous growth
factors
Growth factors influence chemotaxis and cell migration via
mediators
Induce mitosis, extracellular matrix production, and angiogenesis
Signal cell proliferation and influence maturation, differentiation,
and ultimately tissue repair5
“A rich source of cells and proteins that may
optimize the conditions for healing”
•  The “secret” behind PRP
–  Platelet Derived Growth Factor (PDGF)
•  Chemo-attractive for stem cells and endothelial cells
–  Transforming Growth Factor (TGF-α, TGF-β)
•  Promotes differentiation for connective tissue and bone
–  Vascular Endothelial Growth Factor (VEGF)
•  Stimulates angiogenesis and chemo-attractive for osteoblasts
–  Insulin Like Growth Factor I (IGF-1)
•  Anabolic effects, protein synthesis, proliferation of fibroblasts
–  Stromal Derived Factor-1 Alpha (SDF-1α)
•  Chemo-attractive for stem cells and endothelial cells
Table 1: Synopsis of growth factors present in PRP From Peter A.M. Everts et al. Platelet-Rich Plasma and Platelet Gel: A Review6
Absolute Contraindications
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Platelet dysfunction syndrome
Critical thrombocytopenia < 50k
Hypofibrinoginemia
Hemodynamic instability
Septicemia
Relative Contraindications
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*Growth factors act on the cell surface only and do not cause DNA
mutation, therefore there is no mechanism by which growth factors
would result in neoplastic development, and there have been no
reports of this in the literature.6,7 It has been showed that PGF
activate normal not abnormal gene expression.8
Recent use of NSAID’s ≈ 5 – 7 days
Corticosteroid use within 2 weeks
of procedure
Recent fever or illness
Rash at graft donor site or at
receptor site
Cancer — especially hematopoietic
or of bone*
HGB <10 g/dl
Platelet count less than 105/µL
•  Current literature search of “PRP Therapy” yields 1,021
published articles
–  Literature ranges from dental to cardiovascular to veterinary
–  Over 90% of all literature is published after 2009
•  PRP Therapy is in the media
–  “A-Rod: Kobe Bryant considered retirement last season”
–  “Is Platelet-Rich Plasma Therapy Blood Doping?”
Courtesy of http://www.anesthesia-analgesia.org , http://www.latimes.com and http://www.chicagotribune.com/media/photo/2010-04/53411940.jpg
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Athletes from virtually every major professional sport have
undergone PRP therapy
Alex Rodriguez
Kobe Bryant
Tiger Woods
David Wright
Brett Gardner
Rafael Nadal
Troy Polamalu
Hines Ward
Andre Johnson
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Current Uses with or without scientific evidence include among
others:
Chronic Tendinopathies
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Chronic Pain and Osteoarthritis
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Elbow (lateral and medial epicondylitis)
Shoulder (rotator cuff tears)
Hip gluteal, proximal hamstring)
Knee (patellar tendon)
Foot/ankle (Achilles, peroneal, plantar fascia)
Knee (mild to moderate arthritis)
Ankle and foot
Shoulder (glenohumeral and acromioclavicular joint)
Muscle
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Subacute and chronic symptomatic tears
•  Current best evidence literature exists on PRP Therapy in
chronic tendinopathies
–  Mishra and Pavelko (2006)12
–  A prospective cohort comparing PRP injection versus local
anesthetic for refractory lateral epicondylitis
–  Outcome measures included VAS and Mayo elbow scores at 2, 6,
and mean of 25 months
–  Results: 60% pain score improvement at 8wks, 81% at 6 months
and 91% at one year for PRP group
–  No patients treated with PRP worsened; no complications
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Peerbooms et al (2010)13
–  A prospective randomized double blind study comparing PRP
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injection versus corticosteroid for refractory lateral epicondylitis
(>6 months)
Outcome measures included VAS and Disability of the Arm,
Shoulder and Hand (DASH) Scores
Results: Statistically significant improvement at 1 year in the PRP
group (73%) vs. 49% in the steroid group in VAS and DASH.
The PRP group progressively improved while the steroid group
regressed
Conclusions: Treatment of patients with lateral epicondylitis with
PRP reduces pain and significantly increases function exceeding
the benefit from corticosteroid injection
Gosens et al (2011)14
–  2 year follow up
•  Current literature exists on PRP Therapy in osteoarthritis
–  Sanchez et al. (2012)16
–  A preliminary non-controlled prospective study in patients with
hip osteoarthritis underwent PRP injection weekly (x3)
–  Results: Statistically significant reduction in VAS, WOMAC and
Harris hip subscores at 6 months follow up
–  Conclusion: This study supported the safety, tolerability and
efficacy of PRP injections for pain relief and improved function in
a limited number of patients with OA of the hip
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Sampson (2010)17
–  A prospective study to evaluate the clinical effect of PRP in knee
osteoarthritis with 3 PRP injections at 4 week intervals.
–  Outcome measures included VAS, Knee Injury and Osteoarthritis
Scores at 2, 5, 11, 18, and 52 week follow up
–  Study demonstrated significant and almost linear improvement in
VAS, Knee Injury and Osteoarthritis Outcome Scores at 52 week
follow up
–  Conclusions: Positive trends and safety profile could be used to
inspire a larger, blinded, and randomized clinical trial
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Spakova (2012)18
–  Prospective cohort study comparing PRP with HA in treatment of
knee osteoarthritis.
–  Statistically significant improvement in the Western Ontario and
McMaster Universities Osteoarthritis Index in patients receiving
PRP at 3 and 6 months follow up
–  Conclusion: Preliminary findings support the application of
autologous PRP as an effective and safe method in the treatment in
the initial stages of knee osteoarthritis
•  Facet joint arthropathy is a common cause of axial neck and low back
pain
•  Interventions for facet joint arthritis is the second most commonly
performed interventional pain procedure in the US (#1 ESI)
•  Facet joints are true synovial joints
•  Interventional treatment include:
–  Medial Branch Block - diagnostic
–  Intra-articular Steroid Injection
–  Radiofrequency Denervation
–  Surgery
Courtesy of http://www.eorthopod.com/images/ContentImages/spine/spine_lumbar/facet_arthritis/lumbar_facet_arthritis_intro01.jpg
  Based on our current knowledge of PRP therapy and available literature
for use in other synovial joints in the body we plan to perform intraarticular facet joint PRP Therapy for cervical and lumbar facet
arthropathy
  Novel procedure with no published literature available to date
  Pain Team to follow and evaluate patients over 12 months period using
VAS, ODI, Neck Disability Index, and NIH PROMIS
  If initial results are positive, plan for a prospective, randomized, blinded
study comparing PRP Therapy to medial branch radio frequency ablation
(RFA) through the IRB
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%20Values. Retrieved 18 November 2007.
Ganong, William F. (2003). Review of medical physiology (21 ed.). New York: Lange Medical Books/McGraw-Hill. p. 518. ISBN
0-07-121765-7.
Andia I, Sanchez M, Maffulli N. Basic Science: Molecular and Biological Aspects of Platelet-Rich Plasma Therapies. OperTech
Ortho 2012; 22:3-9.
De la Torre j. “The Physiology of Healing of the Chronic Wound”.
http://www.emedicine.com/plastic/topic477.htm #section~the physiology_of_the_chronic_wound. Last updated: May
26,2006.
Nguyen R, Borg-Stein J, McInnis K. Applications of Platelet-Rich Plasma in Musculoskeletal and Sports Medicine: An Evidence
Based Approach. PMR March 2011; 3:226-250.
Everts PAM, Knape JTA, van Zundert A, et al. Platelet Rich Plasma and Platelet Gel: A Review. JECT. 2006. 38: 174-187.
Creaney L and Hamilton B. Growth Factor Delivery Methods in the Management of Sports Injuries: The State of Play. Br J
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Bielecki TM et al. Antibacterial effect of autologous platelet gel enriched with growth factors and other active substances; an in
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Scott JD and Pawson T. Cell communication: The inside story. Sci Am. Jun 2000. pp 54-61
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David et al. Platelet Rich Plasma (PRP) Matrix Grafts. Practical Pain Management. Jan/ Feb 2008. Vol 8 Issue 1: 12-26.
Mishra A, Pavelko T. Treatment of chronic elbow tendinosis with buffered platelet-rich plasma. Am J Sports Med 2006;
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Peerbooms JC, Sluimer J, Bruijn DJ, Gosens T. Positive effect of an autologous platelet concentrate in lateral epicondylitis in a
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Taco Gosens MD/PhD, Joost C Peerbooms MD, Wilbert van Laar, Brenda L den Oudsten PhD.
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 Mar.
Creaney L, Wallace A, Curtis M, et al. Growth factor-based therapies provide additional benefit beyond physical therapy in
resistant elbow tendinopathy: a prospective, single-blind, randomised trial of autologous blood injections versus platelet-rich
plasma injections. Br J Sports Med 2011;45:966–71.
Sanchez M; Guadilla J; Fiz N;Andia I. Ultrasound-guided platelet-rich plasma injections for the treatment of osteoarthritis of
the hip. Rheumatology. 2012. Vol.51,Iss.1;p.144-50.
Samson S et al. Injection of platelet-rich plasma in patients with primary and secondary knee osteoarthritis. Am J Phys Med
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Spakova T, et al. Treatment of knee joint osteoarthritis with autologous platlet-rich plasma in comparison with hyaluronic acid.
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