Review article The use of platelet-rich plasma to augment conservative and surgical treatment of hip and pelvic disorders Matthew J. Kraeutler 1 KEY WORDS: hamstring tendinopathy, hip osteoarthritis, Tigran Garabekyan 2 osteitis pubis, microfracture, platelet-rich plasma. Omer Mei-Dan 3 1 University of Colorado School of Medicine, Introduction Department of Orthopedics, Aurora, USA 2 Platelet-rich plasma (PRP) has gained popularity within Southern California Hip Institute, North Hollywood, the last decade among the orthopaedic community as a CA, USA 3 treatment modality to enhance tissue healing. The term Hip Preservation/ Sports Medicine/Orthopedics platelet-rich plasma may be applied to any fraction of University of Colorado autologous blood that contains a higher concentration of platelets than baseline 1. Thus, this term is non-spe - Corresponding author: cific and factors such as the concentration of platelets Omer Mei-Dan and leukocytes as well as centrifugation methods have Hip Preservation/Sports Medicine/Orthopedics differed between studies. DeLong et al. 2 developed the University of Colorado PAW classification system to aid in comparing different 12631 East 17th Avenue protocols of PRP preparation. This classification system Mail Stop B202, Room L15-4505 is based on the absolute number of platelets (P), the Aurora, Colorado 80045 (USA) method of platelet activation (A), and the presence/ab - E-mail: [email protected] sence of white cells (W). Recently, PRP has been utilized for numerous muscu - loskeletal indications such as rotator cuff repair 3,4 , Summary patellar tendinopathy 5, knee osteoarthritis 6, lateral epi - condylitis 7, osteochondral lesions of the talus 8, and Background: In recent years, platelet-rich plasma many other orthopaedic conditions. PRP induces mus - (PRP) has gained popularity within the orthopaedic culoskeletal healing through a number of effects. As a community as a treatment modality to enhance tis - treatment modality for tendon healing, PRP enhances sue healing. 9 the mobilization of circulation-derived cells . This may Purpose: This review aims to concisely present the include inflammatory cells that secrete cytokines and current indications for PRP injections in the treat - growth factors as well as fibroblast-like cells that syn - ment of hip and pelvic pathologies and to describe thesize matrix. Compared to serum, PRP has been some novel applications for PRP which have not shown to significantly increase the deposition of a colla - yet been reported in the literature. gen-rich extracellular matrix 10 , with higher collagen I 11 Methods : We reviewed the literature on the non-op - content compared to placebo . Interestingly, PRP- erative and operative indications for PRP in the treated tendon tears have actually been shown to con - treatment of hip and pelvic pathologies. tain fewer blood vessels compared to placebo 11 , possi - Conclusions: With regard to hip and pelvic patholo - bly indicating a more physiological healing process. gies, PRP injections are used most commonly as a Once PRP enhances the early phase of regeneration, non-operative intervention, and have been de - mechanical stimulation is required to promote orga - scribed in the literature to treat osteoarthritis of the nized collagen synthesis and remodeling during new 12 hip joint as well as tendinopathy of the hamstrings, tendon development . adductor longus, and gluteus medius. In contrast, With muscle strains or contusions, the hematoma that most of the surgical applications of PRP for the hip originates contains approximately 94% red blood cells, 13 are novel, with few reported studies in the litera - 4% platelets, and <1% leukocytes . Compared to ture. Because of the increasing awareness of PRP’s whole blood, PRP contains higher concentrations of beneficial effects on musculoskeletal healing and certain growth factors, in particular platelet-derived b thus the growing number of indications for its use, growth factor (PDGF) and transforming growth factor- b 14 this review also describes some novel applications (TGF- ) . Thus, PRP is theorized to replace the for PRP, including osteitis pubis, post-microfrac - hematoma with a high concentration of platelets and ture of the hip, tears of the rectus femoris, and growth factors to promote healing. Furthermore, PRP avulsion of the sartorius muscle. has been shown to promote angiogenesis through acti - Level of evidence: V. vation of PRP-releasate (PRP-r) 15 . In comparison to 410 Muscles, Ligaments and Tendons Journal 2016;6 (3):409-419 The use of platelet-rich plasma to augment conservative and surgical treatment of hip and pelvic disorders tendon and muscle healing, little is known on the mech - trate are activated with calcium chloride and/or autolo - anisms of PRP in promoting healing of articular carti - gous or bovine thrombin. These additions are used to lage, though this likely involves multiple biological initiate the clotting cascade, the release of growth fac - processes including apoptosis, extracellular matrix syn - tors from the platelets, and the formation of a fibrin 16 20 thesis, angiogenesis, and inflammation . Because of scaffold . Autologous thrombin has been shown to the increasing awareness of PRP’s beneficial effects on have a lower clot strength compared to bovine thrombin musculoskeletal healing and thus the growing number or calcium chloride, with bovine thrombin having the 21 of indications for its use, we present a review of the quickest clot initiation time . In an equine model, calci - current indications for platelet-rich plasma injections to um chloride activation of PRP has been shown to result augment the conservative and surgical treatment of hip in greater release of platelet-derived growth factor com - 22 and pelvic pathologies and describe some novel appli - pared to autologous or bovine thrombin . Calcium cations for PRP which have not yet been described in chloride also provides the advantage of not using the literature. Although several studies have described bovine or other non-autologous materials. the use of PRP for some of these pathologies, other in - Therapeutic doses of PRP require 2.5-5 times the dications for PRP discussed in this review have not baseline concentration of platelets 23,24 , though higher been published previously. As such, these indications concentrations than this have an inhibitory effect on 25 are not yet evidence-based. This article submits to the healing . The white blood cell concentration may also 17 ethical standards of the journal . be controlled, with leukocyte-rich PRP (L-PRP) and leukocyte-poor PRP (P-PRP) both being used in the lit - erature. For production of L-PRP, the entire layer of the Decision-making buffy coat and few RBCs are transferred to an empty sterile tube, while the upper layer and only the superfi - After performing an appropriate patient history and cial buffy coat are transferred for production of P- 19 physical examination, advanced imaging is typically ob - PRP . Plasma rich in growth factors (PRGF) is a term tained to better characterize the suspected pathology. used to describe a leukocyte-poor PRP which is sepa - With muscle or tendon tears, magnetic resonance rated manually (direct visualization using a fine pipette) imaging (MRI) or ultrasound (US) should be used to de - from the lower fraction of the plasma containing the termine the exact location and extent of the injury. De - highest concentration of platelets and growth factors, pending on the pathology, PRP may be used as a con - avoiding the thin WBC layer. PRGF techniques have servative treatment measure or as adjunctive treatment been shown to produce lower concentrations of growth during surgery. When used as a conservative treatment factors compared to standard PRP kits by 3-4 fold 26 option, PRP may be applicable for tendinopathic which, according to many studies, may serve as the op - changes or partial tendon tears in which the tendon timal ratio for tissue healing. 1 ends are not retracted . When a tendon or muscle is injured, healing proceeds The cost of platelet-rich plasma treatment is certainly a through three processes: inflammation/degeneration, 1 factor in the decision-making process. Insurance com - regeneration, and fibrosis . Although L-PRP has been panies still do not recognize PRP as standard of care, shown to contain the highest levels of growth factors and thus PRP must be paid by patients out of pocket. It and cytokines 27 , it induces catabolic effects and a sig - has been estimated recently that the cost of PRP is nificantly greater acute inflammatory response and thus 18 27-30 $500 to $1,500 per application . It is important to have may actually prolong the healing process . Thus, the an open discussion regarding the cost of PRP injec - inclusion of white cells defeats the purpose of PRP. On tions, given that it may be prohibitively expensive for the other hand, P-PRP induces mainly anabolic some patients. changes, and while this is generally a beneficial out - come, it could also result in scar tissue formation due to 27,30 these anabolic effects . Still, no randomized or Preparation and application techniques prospective clinical studies have been performed to compare outcomes between leukocyte-rich versus A sample of whole blood is collected in a sodium citrate leukocyte-poor PRP. tube in order to delay clotting of the blood sample. Once the whole blood sample is collected, centrifuga - tion allows separation of the sample into its component Non-operative applications cells and serum. Either one or two centrifugation steps may be used depending on the final product desired. A Platelet-rich plasma injections are used most commonly “soft” spin separates the whole blood sample into three as an adjunct to conservative treatment. In cases of layers: an upper layer consisting mainly of plasma and chronic tendinopathy or osteoarthritis, PRP is typically platelets, a very thin middle layer known as the “buffy indicated when first-line treatment (physical therapy, coat” that is highly concentrated in WBCs, and a bot - rest) fails. For professional athletes, in-season PRP 19 tom layer consisting mainly of red blood cells (RBCs) .