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Knee Surgery & Sports Medicine Unit IRCCS Humanitas Clinical Institute, Milan P. Volpi - M. Denti C.Bait M. Cervellin, E. Prospero A. Quaglia PRP in patellar tendinopathies Corrado Bait, MD LONDON, 18 Oct 2012 I have no financial relationships to disclose Corrado Bait, MD WHAT IS PRP • Platelet Rich Plasma (PRP) is a therapy that utilizes a patient’s own blood to stimulate a healing response within a damaged tissue or joint • PRP is made by taking a small sample of a patient’s own blood and spinning in a centrifuge for fifteen minutes • This process concentrates platelets and white blood cells in what is called “buffy coat” that is extracted and delivered to the injuried area • PRP is a sample of autologous blood with concentrations of platelets above baseline values • Growth factors in the platelets recruit and produce cells necessary for healing Arnoczky et al 2011;19(3):142-148 GROWTH FACTORS Factor Principal Source Primary Activity Comments PDGF platelets, endothelial cells, placenta promotes proliferation of connective tissue, glial and smooth muscle cells two different protein chains form 3 distinct dimer forms; AA, AB and BB EGF submaxillary gland, Brunners gland promotes proliferation of mesenchymal, glial and epithelial cells TGF-a common in transformed cells may be important for normal wound healing related to EGF wide range of cells; protein is associated with the ECM promotes proliferation of many cells; inhibits some stem cells; induces mesoderm to form in early embryos at least 19 family members, 4 distinct receptors promotes neurite outgrowth and neural cell survival several related proteins first identified as protooncogenes; trkA (trackA), trkB, trkC FGF NGF kidney promotes proliferation and differentiation of erythrocytes TGF-b activated TH1 cells (Thelper) and natural killer (NK) cells anti-inflammatory (suppresses cytokine production and class II MHC expression), promotes wound healing, inhibits macrophage and lymphocyte proliferation at least 100 different family members, including BMPs IGF-I primarily liver promotes proliferation of many cell types related to IGF-II and proinsulin, also called Somatomedin C IGF-II variety of cells promotes proliferation of many cell types primarily of fetal origin related to IGF-I and proinsulin Erythropoietin Kon E. et al. Platelet-rich plasma (PRP) to treat sports injuries: evidence to support its use. Knee Surg Sports Traumatol Arthrosc (2011) 19:516–527 PRP PROCEDURE Type of PRP P-PRP L-PRP P-PRF Pure-PRP Leukocyte rich PRP Pure Platelet rich Fibrin • Autologous Conditioned Plasma (ACPTM)Arthrex 2.0 x • Preparation Rich in Growth Factor (PRGF) Biotechnology Institute • GPS 3.2 x ® - Biomet • Symphony TM II –DePuy 4.0 x • Cascade ® - Muscoloskeletal transplantation foundation 1.6 x • PRGF scaffold Biotechnology Institute Leukocyte and Platelet Rich Fibrin No specific sistem PRP PROCEDURE Wide variations of Platelets numbers Different preparation methods Intra-individual variability Inter-individual variability Age variability Mazzocca A., et al - 2012 Platelet-rich plasma differs according to preparation method human variability. Are all PRP treatments the same ? NO !!! Because one treatment is not the same as another treatment for different reasons: • Platelets level base it’s different in every patient • There are different type and use of PRP (liquid or gel forms) • Some treatments contain red or white blood cells, thrombin or calcium chloride • The right indications for use are important to understand and for talking about the outcomes of PRP treatments…..we need to make sure we are talking about similar comparisons Vol. 28, N 7, 2012 :pag 998 - 1009 “PAW classification system offers a simple, effective method for quickly documenting the cellular components and activation method used. The acronym PAW is for Platelets, Activation, and White cells, and the subcategories are thoughtfully organized to enhance recall” ITALIAN RULE All blood manipulation must be done under Hospital Hematologic Service Control (DL 19-08-2005 N° 191) PRP CONCENTRATION •Effective concentration it’s about 1 milion/µL, 3 to 5X platelet level baseline • Fibroblasts are better stimulated with concentration around 2,5X Platelet baseline • Expression of Growth Factors receptors decrease with age Weibrich g et al, Bone 34:665-671, 2004 De Mos et al. Am J sports Med 36:1171-1178, 2008 Vavaken P. et al. Age dependence of expression of growth factor receptors in porcine ACL fibroblasts 2010, J Orthop Res 28:1107-1112. PRP in Patellar Tendinopathies • Injection therapy: biological & mechanical action • Improve surgical procedure Clinical applications Multiple PRP injections in patellar tendon with good results Better clinical results Physiotherapy & multiple PRP injection (3 injection) Vs only Physioth • 31 patients • 6 months of follow up PRP PROCEDURE Clinical applications JAMA 2010;13(303):144–149 NO significant difference in painless or functional recovery in PRP Vs placebo study 54 patients (27 each group) • 24 months of follow up • Level 1 of evidence PRP PROCEDURE Clinical applications FINDING NO DIFFERENCE DOES NOT MEAN THERE IS NO DIFFERENCE PRP PROCEDURE Our experience MATERIAL & METHODS Blood sample of 30 ml Spinning GPS® - Biomet 3,2 X PRP PROCEDURE Extraction of Platelet Poor Plasma (PPP) Extraction of Platelet Rich Plasma (PRP) Added to the PRP of sodium bicarbonate (8.4%) to neutralize the PH PRP PROCEDURE Our experience in patellar tendinopathies US guide multiple injection of L-PRP PRP PROCEDURE Post Injection • after 7 days for 3 weeks • swim • ROM recovery • stretching • after 5 weeks • excentric & concentric exercise • after 7 weeks • running • after 9 weeks • sport-specific training • after 12 weeks return to sport PRP PROCEDURE Volpi P et Al. Med Sports 2007;60: 595-603 Statistically significant painless reduction at 90 days of follow up after L-PRP treatment Volpi P et Al J Sports Med Phys Fitness 2010; 50: 494-500 Same better results in other site at 24 months of follow up PRP PROCEDURE Our experience post 120 gg 80 75,00 70 controllo a 24 mesi Visa Score 60 70,29 50 40 Pre 39,25 30 20 10 PRE POST PRP PROCEDURE •Randomized control trial VAS •2008-2009 :40 patients: Pre Post Pre Post CTRL Group 3.8±2.1 1±1.4 59.8±23.2 84.5± 11.8* PRP Group 1.2±2.2 0.6±0. 64.4±18.2 9 97.8± 2.5*§ 20 control group (A) 20 PRP group (B) •F.U. :12 mths (VAS, VISA, RM) VISA PRP PROCEDURE Our experience GOLD MEDAL 1500 MT WOMAN PRP PROCEDURE Multiple scar & L-PRP WADA (The World Anti-Doping Agency) World Anti-doping Code The prohibited list 2010 S2. Peptide Hormones, Growth factors and related substances Platelet-derived preparations (e.g. Platelet Rich Plasma, “blood spinning”) administredred by intramuscolar route. Other routes of administration will require a declaration of use in compliance with the international Standard for Therapeutic Use Exemptions. World Anti-doping Code The prohibited list 2011 – Summary of modifications S2. Peptide Hormones, Growth factors and related substances Intramuscle injection of PRP was removed of WADA prohibited list Take Home Message • More talk than outcomes. Fashion topic • Larger preclinical and clinical studies (RCT) are still needed to define the real benefits and indications of its use • Different procedure and type of PRP, extreme variability of GF. • No standardized indications • Rules & Costs The current evidence shows that stem cells can have a positive effect on tendon healing. This is most likely because stem cells have regeneration potential, producing tissue that is similar to the preinjury state but the results can be variable “The use of adjuncts such as molecular signaling, mechanical stimulation, and augmentation devices can potentially enhance stem cell therapy” Ahmad Z et al; Arthroscopy, Vol 28, No 7 (July), 2012: pp 1018-1029 CONCLUSION GOOD MEDICAL PRACTICE CORRECT INDICATION & THERAPY HIGH LEVEL RESEARCH BIOTECHNOLOGY INNOVATIONS PRP in patellar tendinopathies Corrado Bait, MD LONDON, 18 Oct 2012
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