Medical Policy: 02.01.32
Original Effective Date: August 2007
Reviewed: January 2017
Revised: January 2017
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.
Autologous platelet-derived growth factors (APDGF) also referred to as platelet rich plasma (PRP), platelet gel, autologous platelet gel, platelet rich concentrate, or platelet releasate, have been proposed for the treatment of multiple conditions including but not limited to chronic wound care and orthopedic indications (degenerative cartilage lesions; tendonitis; joint capsular injuries; plantar fasciitis; soft tissue trauma (e.g. tendon and ligament ruptures); fractures; osteoarthritis of the knee; muscle injuries and disorders) to enhance healing.
Autologous platelet derived growth factors (platelet rich plasma (PRP)) utilize an increased concentration of platelets. 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:
Double spinning concentrates the PRP into a much smaller volume than single spinning and provides 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.
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) 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.
PRP may also be used during certain types of surgery for some injuries including Achilles tendon rupture, rotator cuff repair, anterior cruciate ligament (ACL) reconstruction, articular cartilage repair, long bone healing and nonunion repair. Non orthopedic indications include wound care, plastic surgery, trauma surgery and general surgery. 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. Based on review of the literature several systematic reviews reported that the available evidence was poor or limited in the number of studies. Better quality randomized controlled trials are needed to determine the actual benefit of PRP for these surgical applications in which it has been used. Based on study results thus far little or no benefit has been seen when PRP is used in these types of surgical procedures.
For autologous platelet-derived growth factors (APDGF) - platelet rich plasma (PRP), 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 and studies are limited in both size and quality. 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. The evidence is insufficient to determine the effects of the technology on net health outcomes.
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.
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.” Recommendation: Inconclusive (there is a lack of compelling evidence that has resulted in an unclear balance between benefits and potential harm).
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.
Autologous platelet-derived growth factor injections, also referred to as platelet rich plasma (PRP), platelet gel, autologous platelet gel, platelet rich concentrate or platelet releasate are considered investigational for all indications including, but not limited to the following:
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. Overall, limitations of the studies include small patient populations, and lack of a control group and/or comparison to standard therapy. 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.
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