This document addresses the use of recombinant human platelet-derived growth factor (becaplermin [Regranex® ]), antimicrobial silver wound dressings, (for example, Acticoat, Actisorb™ , and Silversorb® ), autologous blood-derived wound products, (for example, Aurix™ [formerly Autologel™ ], Vitagel® ), platelet rich plasma (PRP), and bone marrow aspirate concentrate. Such products have been proposed for the treatment of skin wounds, various musculoskeletal injuries, and during various surgical procedures.
Note: For information regarding the use of other soft-tissue and bone grafting products, please see:
The use of recombinant human platelet-derived growth factor (becaplermin [Regranex]) is considered medically necessary when it is used as an adjunct to standard wound management for either of the indications (1 or 2) below:
Note: Individuals are typically treated once daily for up to 20 weeks or until complete healing occurs with becaplermin.
Investigational and Not Medically Necessary:
The use of recombinant human platelet-derived growth factor (becaplermin [Regranex]) is considered investigational and not medically necessary for the above indications when criteria are not met and for all other applications not listed above as medically necessary, including, but not limited to, the following:
Antimicrobial silver wound dressings, (for example, Acticoat, Actisorb, and Silversorb) are considered investigational and not medically necessary for all applications.
Autologous blood-derived wound products, (for example, Aurix [formerly Autologel], Vitagel) are considered investigational and not medically necessary for all applications.
The use of platelet rich plasma (PRP), including autologous conditioned plasma (ACP), is considered investigational and not medically necessary for all indications, including the treatment of any of the following:
The use of bone marrow aspirate concentrate (BMAC) is considered investigational and not medically necessary for all indications, including for the treatment of critical limb ischemia.
Recombinant platelet-derived growth factor (PDGF, becaplermin gel [Regranex]) has been found to be efficacious as an adjunct to standard wound management for individuals with neuropathic diabetic ulcers and for the treatment of pressure ulcers. These conclusions are based on several well-designed randomized controlled studies. However, efficacy for other uses has not been demonstrated in the literature.
Antimicrobial silver wound dressings (e.g., Acticoat, Actisorb, AQUACEL® AG, Silversorb and Urgotul® Silver) have not been sufficiently evaluated in the peer-reviewed literature. It is not possible to determine their efficacy as a dressing to facilitate wound care because of the limited availability of clinical data. A nonrandomized, non-blinded non-inferiority study by Harding and colleagues published in 2011 compared AQUACEL AG (n=145) to Urgotul Silver (n=136). The results of the study indicate non-inferiority, within a pre-determined non-inferiority margin of -15%. However, it should be noted that the use of either of these products is not well studied in comparison to standard treatment. A study by Biffi and others from 2012 did just that, comparing AQUACEL AG (n=58) in a blinded and randomized manner to standard care (n=54). The authors reported no significant differences between groups with regard to the overall rate of surgical site infections (experimental group, 15.5% vs. controls, 20.4%; p=0.451).
Another non-blinded, RCT involved 24 subjects with diabetic foot ulcers who received treatment with collagen/oxidized regenerated cellulose/silver (COS group) compared to 15 subjects who received standard treatment (Gottrup, 2013). The authors reported that more wounds in the COS group reached 50% wound closure by week 4 (79% [19/24]) compared to the control group (43% [6/14]), (p=0.035). At each time point recorded, there was a higher proportion of improved wounds in the COS group compared with the control group, and the differences were significant at week 4, week 8, and week 10 (p=0.035, p=0.018, p=0.046, respectively). At the end of the study, 91% of wounds in the collagen/ORC/silver treatment group were either healed or showed a reduction in wound size of at least 50% compared to 69% of wounds in the control group. However, this difference was not found to be significant. The number of subjects withdrawing from the study due to wound infection was significantly higher in the control group (31% [4/13]) vs. the COS group (0% [0/23]) (p=0.012). No adverse events were reported to be related to the use of COS. Given this data, further investigation with greater numbers of subjects in a larger number of centers and in different phases of wound care is needed.
In 2015, Ozaki and others published the results of a large RCT involving 500 subjects with lower extremity vascular surgery wounds assigned to post-operative treatment with standard gauze dressing or Acticoat dressing (n=250 per group). The intent-to-treat analysis indicated that there was no significant difference between groups with regard to wound complication rates. The authors concluded that the use of Acticoat provided no benefit with regard to wound complications.
Autologous Blood-derived Products
At this time, there are no published peer-reviewed articles addressing the use of autologous blood-derived wound products, (e.g., Aurix (formerly Autologel), or Vitagel). Therefore, conclusions regarding the efficacy of these preparations cannot be reached.
Platelet Rich Plasma
Platelet rich plasma (PRP) has been available for several decades and its use has been proposed for a wide variety of medical conditions. The medical literature currently lists dozens of studies addressing the use of PRP for a wide variety of indications including chronic skin wounds, maxillofacial and sinus surgery, various musculoskeletal injuries and surgical procedures, endovascular surgery, plastic surgery, and thoracic and cardiac surgery. Unfortunately, most available studies are small, uncontrolled, retrospective, and/or have short follow-up periods, constituting significant methodological flaws which limit the utility of the studies in evaluating the benefits of PRP use.
There are several RCTs published addressing the use of PRP to treat chronic lateral epicondylitis (LE), also known as tennis elbow). The largest RCT available to date involved 230 subjects with chronic LE randomized in a double-blind fashion to receive PRP (n=116) or active controls who received needling only (n=114) (Mishra, 2013). After receiving a local anesthetic, all subjects had their extensor tendons needled with or without PRP. Subjects were followed for up to 24 weeks. No significant differences were noted between groups at 12 weeks (n=192, 83.5%). At 24 weeks (n=119, 51.8%), the PRP-treated subjects reported an improvement of 71.5% in their pain scores compared with 56.1% in the control group (p=0.019). Additionally, 29.1% of the PRP-treated group reported significant elbow tenderness versus 54.0% in the control group (p=0.009). Success rates for the subjects completing the 24 week follow-up period were 83.9% in the PRP group vs. 68.3% in the control group (p=0.037). No significant complications occurred in either group. The authors concluded that at 24 weeks clinically meaningful improvements were found in subjects treated with leukocyte-enriched PRP compared with an active control group. However, these results must be viewed with care, since the loss to follow-up was so large at 24 weeks (48.2%). Peerbooms and others (2010) published an RCT describing the use of PRP in 100 subjects with LE randomly assigned to receive a single injection of PRP (n=51) or corticosteroids (n=49). After 1 year, 25 of the 49 subjects (51%) in the corticosteroid group and 37 of the 51 (73%) in the PRP group were deemed "successful" with greater than 25% reduction in DASH Outcome Measure scores (p=0.005). The authors note that further study of the use of PRP is warranted. Krogh (2013) described a study that involved 60 subjects assigned to receive treatment with a single injection of either PRP, saline, or glucocorticoid. Pain reduction at 3 months was observed in all 3 groups, with no statistically significant difference between the groups (p=0.717). At 1 month, however, glucocorticoid reduced pain more effectively than did both saline and PRP. At 3 months, glucocorticoid was more effective than PRP and saline in reducing color Doppler activity (p=0.0001) and tendon thickness (p=0.002). The authors concluded that a single injection with either PRP or glucocorticoid was not significantly superior to a saline injection for reducing pain and disability over a 3-month period in individuals with LE. Two other RCTs compared PRP to autologous blood injection (ABI). A study by Creaney (2011) involved 150 subjects (n=80 PRP group, n=70 ABI Group). The follow-up for this study was 6 months, and the authors noted that at 6 months the success rate in the PRP group was 66% vs. 72% in the ABI group (p=not significant), and there was a higher rate of conversion to surgery in the ABI group (20%) versus the PRP group (10%). Montalvan (2016) described the results of a double-blind placebo-controlled randomized trial involving 50 subjects assigned to receive either conditioned plasma (n=25) or saline solution (n=25). Subjects were monitored at baseline and 1, 3, 6 and 12 months. The primary outcome was relative improvement from baseline to 6 months in pain score on visual analog scale. The secondary outcome was Roles-Maudsley score and the assessment of pain on isometric contraction of extensor carpi radialis brevis and extensor digitorum communis. Three subjects dropped out from each study group before the 6 month time period. In the PRP group, the pain score decreased significantly from a mean of 6.8 at baseline to 2.5 at 6 months and 1.6 at 12 months. In the saline group the results changed from 7 at baseline to 2.1 and 1.8, respectively. At 6 months, no statistically significant difference was found between groups for relative improvement in pain score (p=0.24). The authors also reported no significant difference between groups with regard to secondary criteria. They concluded that PRP injections, for epicondylitis of recent evolution, were not more efficacious than saline injections. Thanasas (2011) reported on a smaller RCT involving 28 subjects assigned to receive a single injection of either autologous blood or PRP, with 14 subjects in each group. The results indicated that the visual analog pain scale was only significantly different at 6 months, in favor of the PRP group (p<0.5). No statistically significant differences were noted on the pain scale or the Liverpool elbow score. These studies present a mixed picture regarding the possible benefits to PRP therapy for LE.
A systematic review published in 2014 by de Vos and Weir evaluated the available literature on PRP treatment for epicondylar tendinopathy. The authors included six studies that met inclusion criteria, of which four were considered to be of high quality. Of these studies, three high-quality and two low-quality studies showed no significant benefit at the final follow-up measurement or in predefined primary outcome score when compared with a control group. Only one high-quality study showed a beneficial effect of a PRP injection when compared with a corticosteroid injection (corticosteroid injections are harmful in tendinopathy). The conclusion of this analysis was that there is strong evidence that PRP injections are not efficacious in chronic LE.
In 2016, Tsikopoulos and colleagues published the results of a meta-analysis evaluating RCTs involving the use of PRP for tendinopathies vs. either placebo or dry needling. The primary condition treated was epicondylitis in two studies, rotator cuff tendinopathy in two studies, and patellar tendinopathy in the last. The authors identified five studies involving 190 subjects that met inclusion criteria. The buffy coat method of PRP preparation was used in 80% of the studies, and did not involve the use of activated platelets. There was a statistically significant difference in favor of PRP for pain intensity at 2 or 3, and 6 months after intervention (p=0.01) and for functional disability at 3 months after treatment (p=0.01).
The use of PRP for arthroscopic repair of the shoulder has been addressed in several moderately sized RCTs (Carr, 2015; Castricini, 2011; Gumina, 2012; Rodeo, 2012; Ruiz-Moneo, 2013; Weber, 2013). Of these studies, three were double-blind studies (Carr, Ruiz-Moneo, and Weber). All of these trials found no significant benefit to the use of PRP with regard to perioperative morbidity, clinical outcomes, or structural integrity. A meta-analysis conducted by Zhao and colleagues in 2015 involved these studies, except the study by Carr, in addition to several smaller RCTs. Their findings showed that the available evidence does not support the use of PRP for full-thickness rotator cuff repair, and that the majority of studies reported no significant benefit to the addition of PRP to standard surgical repair.
A study by Battaglia (2014) investigated the difference in outcomes between PRP and hyaluronic acid (HA) for the treatment of hip osteoarthritis. This study involved 100 subjects evenly distributed between groups. The authors state that at no time point (1, 3, 6, 12, or 24 months) were significant differences noted between groups with regard to Harris Hip Score or visual analog pain scale ratings. They concluded that PRP was not superior to HA for the treatment of osteoarthritis (OA) of the hip. Another study by Dallari (2016) reported the results of an RCT involving 111 subjects with hip osteoarthritis assigned to treatment with 3 weekly injections of either PRP (n=44), PRP+HA (n=31), or HA alone (n=36). Subjects were followed for 12 months post treatment with no withdrawals or loss to follow-up. At all time points, the PRP group had the lowest VAS pain scores. The authors pointed out that at the 6 month follow-up in particular, the mean VAS score was 21 in the PRP group, 35 in the PRP+HA group, and 44 in the HA group (p<0.0005 for PRP vs. HA and p=0.007 for PRP vs PRP+HA). The McMaster Universities Osteoarthritis Index (WOMAC) score of the PRP group was significantly better at 2-month and 6-month follow-up vs. the other groups, but not at the 12-month follow-up (at 2 months: p<0.009 for PRP vs. HA and p=0.026 for PRP vs PRP+HA; at 6 months: p<0.009 for PRP vs. HA and p=0.0005 for PRP vs PRP+HA; at 12 months: p<0.005 for PRP vs. HA and p=0.007 for PRP vs PRP+HA). Positive response at 12 months was reported for participants in all groups with regard to WOMAC scores (p=0.04), but not with VAS or Harris Hip scores (p=NS).
Two RCTs have investigated the use of PRP for the prevention of tunnel widening following anterior cruciate ligament (ACL) reconstruction surgery (Mirzatolooei, 2013; Vadalà, 2013). These small studies (n=50 and 40, respectively) both reported no significant benefit to the use of PRP to prevent tunnel widening. It is unclear if further studies into this use of PRP would provide data demonstrating any benefit to PRP for this indication.
Seijas (2013) reported the results of an RCT involving 98 subjects evaluating the use of PRP in tendon graft remodeling following ACL reconstruction. The findings, based on MRI studies, indicated that PRP had a significant impact on remodeling, with more subjects in the PRP group vs. controls attaining higher stages of remodeling at 4 months (p=0.003), 6 months (p=0.0001), and 12 months (p=0.354). However, no clinical data is presented, and it is not clear if the level of improved tendon remodeling reported provides any significant clinical outcome benefits. Further investigation is warranted. Another RCT, conducted by Nin et al (2009) involved 100 subjects, 50 receiving standard surgical treatment and 50 undergoing ACL reconstruction with the addition of PRP. There were no significant differences between groups reported with regard to MRI appearance of the graft, inflammatory markers, clinical evaluation scores (visual analog scale, International Knee Documentation Committee), or KT-1000 arthrometer testing. Finally, Vogrin (2010) reported the results of a single-blinded RCT involving 50 subjects receiving similar group placement as used in the Nin study (25 in each group). The authors reported finding a significantly higher level of vascularization in the osteoligamentous interface vs. control group (p<0.001), but no evidence of revascularization in the intra-articular part of the graft. Further investigation into this treatment method is warranted.
An RCT investigating the use of PRP for the treatment of postoperative pain and blood loss following total knee arthroplasty was done by Aggarwal and others (2014). This study randomized 40 subjects (59 knees) who were randomized to receive treatment with PRP (n=17, 27 knees) or without PRP (n=23, 32 knees). In the immediate postoperative period, the PRP group had a significantly lower reduction in hemoglobin and need for blood transfusion (p=0.00 and p=0.001, respectively), experienced less pain (p=0.00), and required fewer narcotics than the control group (p=0.00). At 3 months there was a significant difference in range of motion (p=0.01), no significant difference in wound scores (p=0.311), and a significant difference in Knee Society Score (KSS) and Western Ontario and McMaster Osteoarthritis Index (WOMAC) scores at 12 weeks (p=0.00, p=0.00 respectively). No significant difference was found at 6 months. These findings warrant further investigation.
PRP for the treatment of osteoarthritis of the knee (OA) has been the subject of several RCTs. The largest of these studies involved 176 subjects treated with either PRP or with hyaluronic acid (HA) (Sánchez, 2012). Response was judged based upon 50% decrease in knee pain from baseline to 24 weeks. The authors reported that the rate of response to PRP was 14.1% higher than that seen in the HA group (p=0.044). However, there were no significant differences between groups reported on the pain, stiffness, and physical function scales on the Western Ontario and McMaster Universities Arthritis Index (WOMAC). The next largest RCT involved 120 subjects assigned to undergo unblinded treatment with either PRP (n=60) or with HA (n=60) (Cerza, 2012). At week 4, both groups showed a significant reduction in overall WOMAC score compared with baseline. The difference recorded between the PRP and the HA group was statistically significant (p<0.001) at this time point, with PRP providing significant improvement vs. HA. At weeks 12 and 24, continuous improvement in the subjects treated with PRP was noted, and a slight worsening was reported in subjects treated with HA (p<0.001). Both groups were still significantly better at week 24 compared to baseline. Another RCT, a double-blind study, included 78 subjects randomized to receive one of three treatments: Group A received a single injection of PRP (n=52 knees), Group B received two injections of PRP 3 weeks apart (n=50 knees), and Group C received a single injection of normal saline (n=46 knees) (Patel, 2013). Statistically significant improvement in all WOMAC parameters was noted in groups A and B within 2 to 3 weeks, lasting until the final follow-up at 6 months. A slight, but statistically insignificant, worsening was reported at the 6-month follow-up. The three groups were compared with each other and no improvement was noted in group C as compared with the other two groups (p<0001). No differences were noted between groups A and B, indicating that a single injection of PRP was sufficient to provide benefit. A third non-blinded RCT involved 120 OA subjects assigned to undergo treatment with either PRP (n=60) or HA (n=60). Both the PRP and HA groups demonstrated statistically significant improvement in both clinical evaluation schemes of the WOMAC at the 3- and 6-month follow-up periods with respect to baseline. The PRP group was reported to have had significantly better WOMAC scores at both the 3- and 6-month follow-up times (p<0.01 for both). A small RCT involving 30 subjects with osteoarthritis of the knee was published by Smith (2016). Subjects were assigned treatment with either autologous conditioned plasma or placebo (n=15 each group). The WOMAC scores in the plasma group at 1 week were significantly decreased compared with baseline scores, and the scores for this group remained significantly lower throughout the study duration. At 12 months post-treatment, subjects in the plasma group were reported to have improved their overall WOMAC scores by 78% from their baseline score vs. 7% in the placebo group.
These studies point to promising benefits of PRP therapy for individuals with OA. However, evidence from larger double-blind RCTs is needed to properly evaluate this treatment method.
In 2013, the American Academy of Orthopaedic Surgeons (AAOS) released their guideline addressing treatment of osteoarthritis of the knee. This document addressed the use of PRP, and their recommendation stated: "We are unable to recommend for or against growth factor injections and/or platelet rich plasma for patients with symptomatic osteoarthritis of the knee." Their rationale for this conclusion was provided:
There was a paucity of articles on the use of platelet concentrates in the treatment of osteoarthritis. Sanchez et al. used activated platelet aggregates in a fibrin matrix and Spakova et al. used a platelet concentrate. None of the studies controlled for platelet volume. All studies used hyaluronic acid as the control group.
The studies showed decreased levels of pain in the post injection period but they were not constructed to allow for a comparative analysis of clinical effectiveness. The lack of controlled prospective blinded randomized clinical trials with a placebo control prevent the work group from making any recommendation on the use of platelets or platelet derived growth factor concentrates in the treatment of osteoarthritis of the knee.
The treatment of sternal wound infections (SWI) with PRP has been described in a small number of studies. A large RCT involving 196 subjects who underwent cardiopulmonary bypass at risk of deep SWI (DSWI) were assigned to either application of autologous PRP before sternal wiring (n=97) or no PRP (n=99) (Dörge, 2013). The authors reported no significant differences between groups with regard to the incidence of DSWI (6.2% vs. 3.0%, p=NS). Serraino (2015) reported on the results of an RCT involving 1093 subjects who underwent cardiac surgery through median sternotomy. Subjects were assigned to receive care either with or without PRP applied inside the sternotomy wound prior to closure. The authors reported that the incidence of DSWI was significantly higher in the control group vs. the PRP group (1.5% vs. 0.20%, p=0.043). Superficial sternal wound infections (SSWIs) were reported to also have been significantly higher in the control group vs. the PRP group (2.8% vs. 0.5%, p=0.006).
PRP has been investigated for the treatment of a large number of other conditions, including long bone non-unions (Calori, 2008; Mariconda, 2008), total knee replacement (TKR) surgery (Berghoff, 2006; Everts, 2007; Gardner, 2007), lasik eye surgery (Javaloy, 2013), chronic skin wounds (de Leon, 2011; Frykberg, 2010; Guthrie, 2016; Sakata, 2012), aortic arch repair (Zhou, 2015), degenerative disk disease (Tuakli-Wosornu, 2016), plantar fasciitis (Mahindra, 2016), burn wounds (Brown, 2016), rotator cuff calcification (Verhaegen, 2016), distal radius fracture (Namazi, 2016) and others. As stated above, these studies have small sample sizes and other serious design flaws which prevent the conclusions from being more widely generalized to clinical practice. Additionally, many of these studies concluded that there is little, if any, benefit to the use of PRP. One exception to this is the use of PRP during TKR, where the majority of studies reported significant benefits with regard to improving post-operative blood loss, length of stay and pain ratings. However, most of these small studies recommended the performance of larger studies to verify and confirm these findings.
PRP has also been extensively studied in neurosurgery, especially spinal fusion. Several small randomized controlled trials have been published investigating the use of PRP for improving fusion rates (Carreon, 2005; Feiz-Erfan, 2007; Hee, 2003; Weiner, 2003), none of which reported any significant benefit from PRP use.
In 2012, Hua and others reported the results of a randomized, non-blinded study of PRP vs. Nd-YAG laser treatment for benign cervical ectopy (n=60 in each group). The authors reported complete cure rates of 93.7% for the PRP group and 92.4% for the laser group (p>0.05). Mean time to re-epithelialization was significantly shorter in the PRP group (6.41 ± 2.05 weeks) than in the laser group (8.28 ± 1.72 weeks) (p<0.01). They also noted that the rate of adverse treatment effects (i.e. vaginal discharge or vaginal bleeding) was much lower in the PRP group than in the laser group (p<0.01) and the effects were milder. Eleven subjects in the PRP group had mild or moderate vaginal bleeding after treatment but none had heavy bleeding and of the 25 subjects with vaginal bleeding in the laser group, 2 had heavy bleeding necessitating tamponade. The results of this study are interesting; however, this is the first report in the literature of PRP used for this indication. Further study is warranted.
Overall, the body of data regarding potentially beneficial use of PRP for any condition is of poor quality and of limited use. Large well-designed trials are needed to effectively evaluate the use of PRP in the clinical setting.
Bone Marrow Aspirate Concentrate
The use of bone marrow aspirate concentrate (BMAC) has been proposed for several conditions, including for the treatment of critical limb ischemia (CLI). At this time, the only available evidence in the peer-reviewed published literature addressing BMAC involves a small RCT (Iafrati, 2013) and a small case series study (Kolvenback, 2010), both for the treatment of CLI. The RCT was double-blind and involved 48 subjects assigned to undergo treatment with BMAC (n=34) or sham (n=14) (Iafrati, 2013). The authors noted that this pilot study was not powered to demonstrate statistical significance. However, they did note favorable trends for BMAC vs. control in major amputations (17.6% vs. 28.6%), improved pain (44% vs. 25%), improved ankle brachial index (32.4% vs. 7.1%), improved Rutherford classification (35.3% vs. 14.3%), and quality-of-life scoring better for BMAC in 6 of 8 domains. No adverse events were attributed to the injections and renal function was not reported to have been affected.
Further studies are needed to fully assess the safety and efficacy of BMAC therapy for any condition, including CLI.
The skin is the largest organ of the body. It is composed of two layers, the epidermis and the dermis, and provides functions critical to survival. The skin acts as a protective barrier to fluid losses and dehydration and it protects against infection and injury by providing a barrier to repel bacteria and other organisms. The skin provides sensory contact with our environment that tells us whether we are feeling light touch, pressure, pain, heat, or cold. Damage to the skin that is extensive or prolonged may interfere with these functions or with those of other body systems and may become life threatening in some circumstances.
The treatment of burns and wounds that have failed to heal despite conservative measures, referred to as chronic wounds, pose a significant burden on the population in terms of pain, disability, and decreased quality of life. Chronic wounds may be due to the effects of diabetes, venous insufficiency to the extremities, pressure due to prolonged periods in the same body position, and other types of skin injuries. They can be difficult to treat and may require treatment with various coverings, such as skin graft or other materials to prevent infection, maintain an environment conducive to healing, or provide a medium for re-growth of new skin. Such coverings come in a wide array of types, from synthetic materials, tissues from the individuals themselves (autologous), human donors (allogeneic), or from animals such as cows and pigs (xenographic), or any combination of these materials (composites).
Human platelet-derived growth factors (PDGF, becaplermin [Regranex]), are produced from genetically-engineered yeast cells, into which the recombinant human form of the gene for the B-chain of PDGF has been inserted. The yeast cells read the inserted genes, as if they were their own and produce PGDF as a product of their metabolism. The PGDF is then collected and purified for use in clinical care. On June 6, 2008 the FDA required the following black box warning be placed on the label of Regranex:
An increased rate of mortality secondary to malignancy was observed in patients treated with 3 or more tubes of REGRANEX Gel in a post-marketing retrospective cohort study. REGRANEX Gel should only be used when the benefits can be expected to outweigh the risks. REGRANEX Gel should be used with caution in patients with known malignancy.
Antimicrobial silver wound dressings (e.g., Acticoat, Actisorb, Silversorb) involve a synthetic layer of nylon, rayon etc. coated with silver nanocrystals. It has been proposed that such coatings act as a barrier to infectious agents and kill bacteria before they are able to reach the wound.
Autologous wound care treatment may include a skin graft, which is a piece of skin from another site on the individual's body moved to the wound site. This method is frequently the preferred treatment, however, this method actually creates a new wound at the site where the graft was harvested, adding to the risk of infection and other complications.
Platelet rich plasma (PRP) is a substance derived from an individual's own blood, after high-speed centrifugation. It functions by re-creating the final phase in normal blood coagulation that produces a fibrin clot, adhering to the application site and providing wound coverage and stabilization. Additionally, PRP may increase the concentrations of beneficial healing factors within the application site, also potentially augmenting the healing effect. PRP's other proposed benefits include the fact that it is autologous and thus not immunoreactive, it is absorbable, and it is fairly simple to produce. Research of potential uses for PRP has been ongoing, including wound care, burns, orthopedics, maxillofacial surgery, plastic surgery, and others.
Another autologous method involves products derived from the individual's own blood growth factors, which are collected from the blood (e.g., Aurix or Vitagel). To make these types of products, blood is drawn from the individual and is centrifuged at high speeds to separate the blood components from one another. The platelet rich plasma portion of the blood is activated with various reagents to convert the blood protein fibrinogen into fibrin, one of the major components required to form a blood clot. This fibrin-rich gel-like substance is then immediately applied to the wound to form a wound covering.
Vitagel is a product that uses an individual's own blood mixed with microfibrillar collagen and thrombin to create an artificial scab on wounds. It has been proposed that this product may assist in controlling bleeding during operative procedures and other circumstances where bleeding may be of concern.
BMAC is an autologous substance that has been proposed as an adjunct to several medical therapies, including for critical limb ischemia. It is collected via needle aspiration of bone marrow which is then processed and re-injected into the individual being treated.
Antimicrobial silver wound dressing (e.g., Acticoat, Actisorb, and Silversorb): A technology proposed to prevent wound adhesion, limit nosocomial (hospital) infections, control bacterial growth, and facilitate burn wound care through a silver-coated dressing material. It consists of layers of a silver-coated synthetic mesh.
Autologous: A product derived from the individual's own body or body products.
Autologous conditioned plasma (ACP): A type of PRP, which is distinguished from other PRP products by a low concentration of white blood cells that may be detrimental to the healing process when present in high concentrations.
Growth factors: Products that play important roles in the regulation of cell division and tissue propagation.
Human-derived autologous wound factor gel (e.g., Aurix, Vitagel): A product that is derived from blood taken from an individual to create a platelet-rich plasma preparation for the treatment of wounds.
Platelet rich plasma (PRP): A preparation made of concentrated platelets from autologous blood; this substance has been suggested for use to improve healing for a wide variety of medical conditions.
The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.
When services may be Medically Necessary when criteria are met:
|S0157||Becaplermin gel 0.01%, 0.5 gram [Regranex® ]|
|E08.40-E08.49||Diabetes mellitus due to underlying condition with neurological complications|
|E08.621-E08.622||Diabetes mellitus due to underlying condition with foot ulcer, other skin ulcer|
|E09.40-E09.49||Drug or chemical induced diabetes mellitus with neurological complications|
|E09.621-E09.622||Drug or chemical induced diabetes mellitus with foot ulcer, other skin ulcer|
|E10.40-E10.49||Type 1 diabetes mellitus with neurological complications|
|E10.621-E10.622||Type 1 diabetes mellitus with foot ulcer, other skin ulcer|
|E11.40-E11.49||Type 2 diabetes mellitus with neurological complications|
|E11.621-E11.622||Type 2 diabetes mellitus with foot ulcer, other skin ulcer|
|E13.40-E13.49||Other specified diabetes mellitus with neurological complications|
|E13.621-E13.622||Other specified diabetes mellitus with foot ulcer, other skin ulcer|
|L97.101-L97.929||Non-pressure chronic ulcer of lower limb, not elsewhere classified|
|L98.411-L98.499||Non-pressure chronic ulcer of skin, not elsewhere classified|
When services are Investigational and Not Medically Necessary:
For the procedure and diagnosis codes listed above when criteria are not met or for all other diagnoses not listed; or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.
When services are also Investigational and Not Medically Necessary:
For the following procedure codes or when the code describes a procedure or product indicated in the Position Statement section as investigational and not medically necessary.
|20999||Unlisted procedure, musculoskeletal system, general [when specified as harvesting and injection of bone marrow aspirate concentrate]|
|0232T||Injection(s), platelet rich plasma, any tissue, including image guidance, harvesting and preparation when performed|
|Note: CPT procedure code 20926 Tissue grafts, other (eg, paratenon, fat, dermis) is not an appropriate code for injection or application of PRP; this code represents harvesting of a tissue graft which is not addressed in this document|
|A4649||Surgical supply, miscellaneous [no specific code for antimicrobial silver wound dressings (e.g., Acticoat, Actisorb, AQUACEL Ag, Promogran Prisma, Silversorb, Urgotul Silver)]|
|G0460||Autologous platelet rich plasma for chronic wounds/ulcers, including phlebotomy, centrifugation, and all other preparatory procedures, administration and dressings, per treatment [for example, Aurix]|
|S9055||Procuren or other growth factor preparation to promote wound healing|
|Note: HCPCS code P9020 Platelet rich plasma, each unit is not specific to autologous PRP; if used to describe autologous PRP it would be considered investigational and not medically necessary|
Peer Reviewed Publications:
Government Agency, Medical Society, and Other Authoritative Publications:
|Websites for Additional Information|
Growth Factors for Wound Healing
The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.
|Reviewed||02/02/2017||Medical Policy & Technology Assessment Committee (MPTAC) review. Updated formatting in Position Statement section. Updated Rationale, References, and Index sections.|
|Revised||02/04/2016||MPTAC review. Added Aurix to Investigational and Not Medically Necessary statement. Removed Safeblood from document. Updated Rationale, Coding and References sections. Removed ICD-9 codes from Coding section.|
|Reviewed||02/05/2015||MPTAC review. Added clarification that 'autologous conditioned plasma' is a type of PRP. Updated Rationale and References sections.|
|Revised||02/13/2014||MPTAC review. Added investigational and not medically necessary statement addressing bone marrow aspirate concentrate. Updated Rationale, Coding and References sections.|
|Reviewed||05/09/2013||MPTAC review. No change to position statement. Updated Rationale and References sections. Updated Coding section with 07/01/2013 HCPCS changes.|
|New||05/10/2012||MPTAC initial document development.|