Autologous Platelet-derived Growth Factors


» Summary» Procedure Codes
» Description» Selected References
» Prior Approval» Policy History
» Policy
 

Medical Policy: 02.01.32 
Original Effective Date: August 2007 
Reviewed: January 2016 
Revised: January 2016 


Benefit Application:

Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.

This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.

Description:

Autologous platelet-derived growth factors (APDGF) also referred to as platelet rich plasma (PRP), platelet gel, platelet rich concentrate, autologous platelet gel, or platelet releasate, have been investigated for the treatment of multiple conditions including but not limited to chronic wound care and orthopedic indications to enhance healing. 

 

Platelets are small fragments that circulate in the blood. They are formed from fragmentation of precursor cells called megakaryocytes, and they have natural lifespan of approximately one week. In response to an acute injury, the body usually produces blood clots. During the formation of blood clots, platelets release their contents (a process referred to as degranulation). Platelets are rich in assorted cytokines (chemicals that attract specific cells) and growth factors such as platelet-derived growth factor and transforming growth factor beta, among many others. The growth factors and cytokines released by platelets as the clot forms assist the body in repairing the damage. The fibrin formed during the clotting process acts as a scaffold for wound healing.  

 

Autologous platelet concentrate suspended in plasma, also known as platelet-rich plasma (PRP), is prepared from whole blood collected from the patient using a standard peripheral vein puncture procedure followed by simple centrifuge or filtration techniques that remove most of the larger cells (white and red blood cells) and the majority of the fluid, and concentrate the platelets in a small volume of plasma (the liquid component of the blood). The concentration of platelets and, thereby, the concentration of growth factors can be 5 to 10 times greater or richer than usual. Many different methods exist for preparing PRP. These methods can be broadly classified into three categories: 1) double spinning in a centrifuge, 2) single spinning in a centrifuge, and 3) filtration. Double spinning concentrates the PRP into a much smaller volume than single spinning and providers a purer product. Commercial kits are available for preparing PRP using any of the three methods, but PRP can also be prepared manually using standard equipment present in most clinical laboratories.

 

PRP can be applied as is or gelled by activating the clotting process (platelet rich gel); it can also be turned into a membrane like substance (platelet rich fibrin matrix). Different preparation methods are likely to yield substances with different properties that may have different clinical effectiveness. 

 

Although it is not exactly clear how PRP works, many experts have speculated that chronic, painful, degenerative conditions of the connective tissues, such as tendinopathies and osteoarthritis, are the result of failed or inadequate healing responses to repeated subacute injuries. Because connective tissues often have limited blood circulation, they have only a limited innate ability to repair the damages of daily wear and tear. Thus, if such damage regularly exceeds the daily repair capacity, the damage will slowly accumulate until the tissue function becomes impaired. Because the tissues do not suffer an acute insult, the acute healing pathways are not triggered to assist in healing the accumulated damage. Therefore, practitioners speculate that if the acute healing pathways can be activated, the body can be induced to repair the damage. Injection of PRP into the injury site is thought to stimulate an acute injury and may induce an acute healing process.   

 

PRP may also be used during certain types of surgery for some injuries, this is done by preparing the PRP in a special way that allows it to actually be stitched into torn tissues to help the tissues heal. It has been thought to be beneficial in shoulder surgery to repair torn rotator cuff tendons and in anterior cruciate ligament repairs. However, based on study results thus far little or no benefit has been seen when PRP is used in these types of surgical procedures.  

 

Autologous platelet-derived growth factor (i.e. AutoloGel, SafeBlood and Procuren) is suggested for use in the management of chronic non-healing wounds. The Agency for Health Care Policy and Research’s (AHRQ) Practice Guideline Treatment of Pressure Ulcers concluded the effectiveness of growth factors for this indication has not been sufficiently established to warrant recommendation for use. Based on review of the peer reviewed medical literature there is insufficient evidence of the effectiveness of autologous platelet rich plasma (PRP) or autologous platelet derived growth factor (PDGF) in improving healing in chronic non healing wounds or for acute surgical wounds when the autologous PRP is applied directly to the closed incision or dehiscent wounds.       

 

For PRP treatment, there are numerous small controlled trials for a wide variety of conditions. The potential benefit of PRP has received considerable interest due to the appeal of a simple, safe, low-cost and minimally invasive method of applying growth factors.  However, current results of PRP trials are mixed. A recent systemic review found that a greater portion of the studies reported no benefit from PRP than studies that reported a benefit. It is unknown if the mixed results are due to variability in the conditions studied and outcomes measured, to differences in platelet separation technique, concentration or activation, or to differences in the timing and frequency of administration. Additional studies are needed to resolve these issues.    

 

Practice Guidelines and Position Statements

 

National Institute for Health and Care Excellence (NICE)
In 2014, NICE issued guidance on the use of platelet rich plasma injections for osteoarthritis of the knee. NICE concluded that the current evidence on platelet-rich plasma injections for osteoarthritis of the knee raises no major safety concerns; however, the evidence on efficacy is inadequate in quality. NICE recommends this procedure should only be used with special arrangements for clinical governance, consent and audit or research.

 

In 2013, NICE issued guidance on the use of autologous blood injection (with or without techniques for producing PRP) for plantar fasciitis. NICE concluded that the current evidence on autologous blood injections for plantar fasciitis raises no major safety concerns. The evidence on efficacy is inadequate in quantity and quality. NICE recommends this procedure should only be used with special arrangements for clinical governance, consent and audit or research.

 

In 2013, NICE issued guidance on the use of autologous blood injection for tendinopathy (this replaces previous guidance on autologous blood injection – interventional guidance 279, January 2009). NICE concluded that the current evidence on autologous blood injection for tendinopathy raises no major safety concerns. The evidence on efficacy remains inadequate, with few studies available that use appropriate comparators. NICE recommends this procedure should only be used with special arrangements for clinical governance, consent and audit for research.      

 

American Academy of Orthopaedic Surgeons (AAOS)
In 2013, the AAOS issued guidance on the treatment of osteoarthritis of the knee, evidence based guideline 2nd edition, which states “were unable to recommend for or against growth factor injections and/or platelet rich plasma for patients with symptomatic osteoarthritis of the knee.” An inconclusive recommendation means that there is a lack of compelling evidence that has resulted in an unclear balance between benefits and potential harm.


Regulatory Status
Blood products such as platelet rich plasma (PRP) are regulated by the Center for Biologics Evaluation and Research (CBER). CBER is responsible for regulating human cells, tissues, and cellular and tissue based products. The regulation process for these products is described in the U.S. Food and Drug Administration (FDA) 21 CFR 1271 of the Code of Federal Regulations. Under these regulations, certain products including blood products such as PRP are exempt and therefore do not follow the traditional FDA regulatory pathway. To date, FDA has not attempted to regulate activated PRP.
 
There are numerous  PRP preparation systems on the market today with FDA clearance. Many of these systems have 510(k) clearance for producing platelet-rich preparations intended to be used to mix with bone graft materials to enhance bone grafting properties in orthopedic practices. The Aurix SystemTM (previously called AutoloGelTM from Cytomedix) and SafeBlood® (SafeBlood Technologies) are two related but distinct autologous blood-derived preparations that can be prepared at the bedside for immediate application. Both AutoloGel and SafeBlood have been specifically marketed for wound healing. Other devices may be used in the operating room setting, such as Medtronic Electromedics, Elmd-500 Autotransfusion System, the Plasma Saver device, or the Smart PreP device. The Magellan Autologous Platelet Separator System (Medtronic) includes a disposable kit designed for use with the Magellan Autologous Platelet Separator portable tabletop centrifuge. BioMet Biologics received marketing clearance through FDA’s 510(k) process for a gravitational platelet separation system (GPS®II), which uses a disposable separation tube for centrifugation and a dual cannula tip to mix the platelets and thrombin at the surgical site. Filtration or plasmapheresis may also be used to produce platelet-rich concentrates. The use of different devices and procedures can lead to variable concentrations of active platelets and associated proteins, increasing variability between studies of clinical efficacy.   

 

Procuren® (Cytomedix, Inc.) an autologous product that has been used as treatment in the past for chronic wound healing, but it is no longer manufactured or commercially available.


Prior Approval:

 

Not applicable


Policy:

Autologous platelet-derived growth factor injections, platelet rich plasma, and autologous platelet gels are considered investigational for all indications including, but not limited to the following:

  • As a treatment of chronic non-healing wounds
  • Plantar fasciitis
  • Epicondylitis
  • Achilles tendinopathy/Achilles tendon rupture 
  • Dupuytren's  contracture
  • ACL reconstruction
  • Rotator cuff repair
  • Spinal fusion
  • Tonsillectomy
  • Osteochondral lesions
  • Osteoarthritis (knee and hip)
  • Ganglion cyst
  • Fractures, including long bone non-union
  • Osteonecrosis of the jaw
  • Soft tissue trauma (e.g. tendon and ligament rupture/tears)
  • Tendonopathies (e.g. elbow, heel, knee, shoulder)
  • Acute joint injuries (sprains/strains)
  • Muscle injuries
  • Subacromial decompression surgery

The evidence based on the efficacy of autologous platelet-derived growth factors (APDGF) (e.g. platelet rich plasma (PRP), platelet gel, platelet rich concentrate, autologous platelet gel, or platelet releasate), treatment consists of numerous small controlled trials for a wide variety of conditions. Current results of PRP trials are mixed, with some trials reporting improvement with PRP and other trials reporting no improvement. It is unknown if the mixed results are due to variability in the conditions studied and outcomes measured, to differences in platelet separation technique, concentration or activation, or to differences in the timing and frequency of administration. Additional studies are needed to resolve these issues. There is inadequate evidence in the peer reviewed medical literature to support clinical effectiveness and therefore is considered investigational for all indications.





Procedure Codes and Billing Guidelines:

  • To report provider services, use appropriate CPT* codes, Modifiers, Alpha Numeric (HCPCS level 2) codes, Revenue codes, and/or diagnosis codes.
  • 0232T Injecton(s), platelet rich plasma, any tissue, including image guidance, harvesting and preparation when performed
  • G0460 Autologous platelet rich plasma for chronic wounds/ulcers, including phlebotomy, centrifugation, and all other preparatory procedures, administration and dressings, per treatment
  • S9055 Procuren or other growth factor preparation to promote wound healing

Selected References:

  • Kiter E, Celikbas, E, Akkaya S et al. Comparison of injection modalities in the treatment of plantar heel pain: a randomized controlled trial. J Am Podiatr Med Assoc. 200696(4):293-6.
  • Logan LR, Klamar K, Leon J et al. Autologous blood injection and botulinum toxin for resistant plantar fasciitis accompanied by spasticity. Am J Phys Med Rehabil. 2006;85(8):699-703.
  • Barrett SJ, Erredge SE. Growth factors for chronic plantar fasciitis. Podiatry Today. 2004;17(11):36-42.
  • Eppley BL, Woodell JE, Higgins J. Platelet quantification and growth factor analysis from platelet-rich plasma: implications for wound healing. Plast Reconstr Surg 2004; 114(6):1502-8.
  • McAleer JP, Kaplan E, Persich G. Efficacy of concentrated autologous platelet-derived growth factors in chronic lower-extremity wounds. J Am Podiatr Med Assoc 2006; 96(6):482-8.
  • Mishra A, Pavelko T. Treatment of Chronic Elbow Tendinosis with Buffered Platelet-Rich Plasma. Am J Sports Med 2006; 34(11):1774-8.
  • Martinez-Zapata MJ, Marti-Carvajal A, Sola I et al. Efficacy and safety of the use of autologous plasma rich in platelets for tissue regeneration: a systematic review. Transfusion 2009; 49(1):44-56.
  • Mishra A, Woodall J Jr, Vieira A. Treatment of tendon and muscle using platelet-rich plasma. Clin Sports Med 2009; 28(1):113-25.
  • Kon E, Buda R, Filardo G et al. Platelet-rich plasma: intra-articular knee injections produced favorable results on degenerative cartilage lesions. Knee Surg Sports Traumatol Arthrosc. 2009 Oct 17. [Epub ahead of print]
  • de Vos RJ, Weir A, van Schie HTM et al. Platelet-rich plasma injection for chronic Achilles tendinopathy. A Randomized Controlled Trial. JAMA. 2010; 303(2):144-49.
  • Almdahl SM, Veel T, Halvorsen P et al. Randomized prospective trial of saphenous vein harvest site infection after wound closure with and without topical application of autologous platelet-rich plasma. Eur J Cardiothorac Surg. 2011 Jan;39(1):44-8. Epub 2010 Jul 15.
  • Castillo TN, Pouliot MA, Kim HJ et al. Comparison of growth factor and platelet concentration from commercial platelet-rich plasma separation systems. Am J Sports Med. 2011 Feb;39(2):266-71. Epub 2010 Nov 4.
  • Peerbooms JC, Sluimer J, Bruijn DJ et al. Positive effect of an autologous platelet concentrate in laterla epicondylitis in a double-blind randomized controlled trial: platelet-rich plasma versus corticosteroid injection with a 1-year follow-up. Am J Sports Med. 2010 Feb;38(2):255-62.
  • Kazakos K, Lyras DN, Verettas D et al. The use of autologous PRP gel as an aid in the management of acute trauma wounds. Injury. 2009 Aug;40(8):801-5. Epub 2008 Aug 13.
  • Castricini R, Longo UG, De Benedetto M et al. Platelet-rich plasma augmentation for athroscopic rotator cuff repair: a randomized controlled trial. Am J Sports Med. 2011 Feb;39(2):258-65. Epub 2010 Dec 15.
  • Margolis DJ, Bartus C, Hoffstad O et al. Effectiveness of recombinant human platelet-derived growth factor for the treatment of diabetic neuropathic foot ulcers. Wound repair Regen 2005; 13(6):531-6.
  • Niezgoda JA, Van Gils CC, Frykberg RG et al. Randomized clinical trial comparing OASIS Wound Matrix to Regranex Gel for diabetic ulcers. Adv Skin Wound Care 2005; 18(5 pt 1):258-66.
  • ECRI. Platelet-derived Growth Factors for Treating Chronic, Nonhealing Wounds. Health Technology Assessment Service. Plymouth Meeting (PA): ECRI InstituteExternal Site; 2012 March 20. [Hotline Service].
  • ECRI. Growth Factors for Treating Chronic Plantar Fasciitis. Health Technology Assessment Service. Plymouth Meeting (PA): ECRI InstituteExternal Site; 2012 March 20. [Hotline Service].
  • Sheth U, Simunovic N, Klein G, et al. Efficacy or autologous platelet-rich plasma use for orthopaedic indications: a meta-analysis. J Bone Joint Surg Am. 2012 Feb 15; 94(4):298-307.
  • Carter MJ, Fylling CP, Parnell LK. Use of platelet rich plasma gel on wound healing: a systematic review and meta-analysis. Eplasty. 2011;11:e38. Epub 2011 Sep 15.
  • Martinez-Zapata MJ et al. Autologous platelet-rich plasma (PRP) for chronic wounds. Cochrane Summaries. 2012 Oct. 17 Accessed [Accessed May 28, 2013]
  • National Institute for Health and Clinical ExcellenceExternal Site. Autologous blood injection for plantar fasciitis. NICE interventional procedure guidance 437. 2013.
  • American Academy of Orthopaedic Surgeons, clinical practice guideline (CPG) on the treatment ofosteoarthritis of the knee 2nd EditionExternal Site. May 2013.
  • Agency for Healthcare Research and Quality (AHRQ), Treatment of Pressure Ulcers, AHCPR Clinical Practice GuidelinesExternal Site, No. 15, December 1994.
  • National Institute for Health and Clinical Excellence (NICE)External Site. Autologous Blood Injection for Tendinopathy, Interventional Procedure Guidance (IPG438), Published January 2013.
  • National Institute for Health and Clinical Excellence (NICE)External Site. Platelet-rich Plasma Injections for Osteoarthritis of the Knee, Interventional Procedure Guidance (IPG491), Published May 2014.
  • ECRIExternal Site. Platelet-rich Plasma Therapy for Osteoarthritis and Acute Joint Injury. Published 11/3/2009, Updated 5/15/2013.
  • ECRIExternal Site. Autologous Platelet-rich Plasma Therapy for Knee Osteoarthritis, Published 2/13/2013.
  • ECRIExternal Site. Platelet-rich Plasma Injections for Treating Chronic Tendinopathies. Published 7/23/2012.
  • ECRIExternal Site. Autologous Blood Injections for Treating Tendinopathies. Published 2/12/2013.
  • ECRIExternal Site. Guidelines for Using Platelet-rich Plasma in Surgical Procedures. Published 11/11/2015.
  • UpToDateExternal Site. Overview of Management of Overuse (Chronic) Tendinopathy, Karim Khan, M.D., Alex Scott PhD, RPT. Topic last updated August 19, 2015.
  • UpToDateExternal Site. Epicondylitis (Tennis and Golf Elbow), Neeru Jayanthi, M.D., Topic last updated September 29, 2015.
  • UpToDateExternal Site. Investigational Approaches to the Pharmacologic Therapy of Osteoarthritis, Kenneth C. Kalunian, M.D., Topic last updated February 17, 2015.
  • UpToDateExternal Site. Plantar Fasciitis. Rachelle Buchbinder, MBBS, MSc, PhD, FRCP, Topic last updated October 30, 2014.
  • OrthoInfoExternal Site. Platelet-Rich Plasma (PRP). Contributed by Frank B. Kelly, M.D., last reviewed September 2011.
  • PubMed. Rabago D, Best TM, et. al. A systematic review of four injection therapies for lateral epicondylosis: prolotherapy, polidocanol, whole blood and platelet –rich plasma, BR J Sports Med 2009 Jul;43(7):471-81
  • PubMed. Creaney L, Wallace A, Curtis M, Connell D, Growth factor-based therapies provided 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 Sep;45(12):966-71
  • PubMed. Krogh TP, Bartels EM, et. al. Comparative effectiveness of injection therapies in lateral epicondylitis: a systematic review and network meta-analysis of randomized controlled trials, AM J Sports Med 2013 Jun;41(6):1435-46
  • PubMed. Hoksrud AF, Bahr R. Injectable agents derived from or targeting vascularity: has a clinical acceptance in managing tendon disorders superseded scientific evidence? J Musculoskeletal Neuronal Interact 2011 Jun;11(2):174-84
  • PubMed. Van Ark M, Zwerver J, et. al. Injection treatments for patellar tendinopathy, Br J Sports Med 2011 Oct;45(13):1068-76
  • PubMed. Murphy RJ, Carr AJ, Shoulder Pain, BMJ Clin Evid 2010 Jul;07.1107
  • PubMed. Sadoghi P, Rosso C, et. al. The role of platelets in the treatment of Achilles tendon injuries, J Orthop Res 2013 Jan;31(1):111-8
  • PubMed. Figueroa D, Figueroa F, et. al. Platelet-rich plasma use in anterior cruciate ligament surgery: systemic review of the literature. Arthroscopy 2015 May;31(5):981-8
  • PubMed. Dold AP, Zywiel MG, et. al. Platelet-rich plasma in the management of articular cartilage pathology: a systematic review, Clin J Sport Med 2014 Jan;24(1):31-43
  • PubMed. Liao HT, Marra KG, Rubin JP. Application of platelet-rich plasma and platelet-rich fibrin in fat grafting: basic science and literature review, Tissue Eng Part B Rev 2014 Aug;20(4):267-76
  • PubMed. Vannini F, Di Matteo B, et. al. Platelet-rich Plasma for foot and ankle pathologies: a systematic review, Foot Ankle Surg 2014 Mar20(1)2-9
  • PubMed. Metcalf KB, Mandelbaum BR, Mcllwraith CW. Application of Platelet-Rich Plasma to Disorders of the Knee Joint, Cartilage 2013 Oct;4(4):295-312
  • PubMed. Lenza M, Ferraz Sde B, et. al. Platelet-rich plasma for long bone healing, Einstein (Sao Paulo) 2013 Jan-Mar 11(1):122-7
  • PubMed. Griffin XL, Wallace D, et. al. Platelet rich therapies for long bone healing in adults. Cochrane Database Syst Rev. 2012 Jul 11:7 CD009496
  • PubMed. Sheth U, Simunovic N, et. al. Efficacy of autologous platelet-rich plasma use for orthopaedic indication: a meta-analysis. J Bone Joint Surg Am 2012 Feb 15;94(4):298-307
  • PubMed. Sommeling CE, Heyneman A, et. al. The use of platelet-rich plasma in plastic surgery: a systemic review. J Plast Reconstr Aesthet Surg 2013 Mar 66(3):301-11
  • PubMed. Cai YZ, Zhang C, Lin XJ. Efficacy of platelet-rich plasma in arthroscopic repair of full-thickness rotator cuff tears: a meta analysis. J Shoulder Elbow Surg 2015 Dec:24(12):1852-9
  • PubMed. Warth RJ, Doman GJ, et. al. Clinical and structural outcomes after arthroscopic repair of full-thickness rotator cuff tears with ad without platelet-rich product supplementation: a meta-analysis and meta-regression. Arthroscopy 2015 Feb;31(2):306-20
  • PubMed. Yan J, Sun Y, et. al. Can patients get better clinical outcomes by using PRP in rotator cuff repair: a meta-analysis of randomized controlled trials. J Sports med Phys Fitness 2015 Oct 16
  • PubMed. Zhao JG, Zhao L. et. al. Platelet-rich plasma in arthroscopic rotator cuff repair: a meta-analysis of randomized controlled trials. Arthroscopy 2015 Jan;31(1):125-35
  • PubMed. Vavken P, Sadoghi P, et. al. Platelet-Rich Plasma Reduces Retear Rates After Arthroscopic Repair of Small and Medium Sized Rotator Cuff Tears but Is not Cost Effective. Am J Sports Med 2015 Dec;43(12):3071-6
  • Ramos-Torrecillas J, De Luna-Bertos E, et. al. Clinical utility of growth factors and platelet-rich plasma in tissue regeneration: a review, Wounds volume 26 issue 7 July 2014

Policy History:

 

January 2016 - Annual Review, Policy Revised

February 2015 - Annual Review, Policy Revised

April 2014 - Annual Review, Policy Revised

May 2013 - Annual Review, Policy Revised

May 2012 - Annual Review, Policy Renewed

August 2011 - Annual Review, Policy Renewed


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*Current Procedural Terminology © 2012 American Medical Association. All Rights Reserved.