Medical Policy: 02.01.61 

Original Effective Date: November 2019 

Reviewed: November 2020 

Revised: November 2020 

 

Notice:

This policy contains information which is clinical in nature. The policy is not medical advice. The information in this policy is used by Wellmark to make determinations whether medical treatment is covered under the terms of a Wellmark member's health benefit plan. Physicians and other health care providers are responsible for medical advice and treatment. If you have specific health care needs, you should consult an appropriate health care professional. If you would like to request an accessible version of this document, please contact customer service at 800-524-9242.

 

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:

The use of platelet-rich plasma (PRP) (also referred to autologous platelet-derived growth factors [APDGF], has been utilized in the treatment of chronic wounds or acute surgical and traumatic wounds, various musculoskeletal (orthopedic) conditions, as an adjunctive procedure in orthopedic surgeries and for other miscellaneous non-orthopedic indications, including but not limited to, androgenetic alopecia, alopecia areata, cerebral palsy, Crohn’s disease related perianal fistula, urethral stricture, and vitiligo. This medical policy will address the use of platelet-rich plasma (PRP) for the treatment of non-orthopedic indications. For platelet-rich plasma (PRP) in the treatment of orthopedic indications see medical policy 02.01.32 and for the use of platelet-rich plasma in combination with mesenchymal stem cells see medical policy 08.01.22 Stem Cell Therapy for Orthopedic Indications (Including Allograft Bone Products used with Stem Cells)*.

 

The blood contains small solid components (red cells, white cells and platelets). The platelets are best known for their importance in clotting blood. However, platelets also contain an abundance of proteins called growth factors (GFs) and cytokines which are suggested to promote healing and/or tissue growth enhancing the body's inherent capacity to repair and regenerate. Platelet-rich plasma (PRP), is extracted from a small quantity of blood collected from the patient using a standard peripheral vein puncture procedure followed by simple centrifuge to 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) that is platelet-rich. The concentration of platelets and, thereby, the concentration of growth factors (GFs) can be 5 to 10 times greater or richer than usual. Although it is not exactly clear how PRP works, it is suggested that the increased concentration of growth factors in PRP stimulate the healing and growth of new structures.

 

Clinical Context and Therapy Purpose

The purpose of platelet rich plasma (PRP) injections is to provide a treatment option that is an alternative to or an improvement on existing therapies.

 

Patients

The relevant population of patients are individuals with androgenetic alopecia, alopecia areata, cerebral palsy, Crohn’s disease related perianal fistula, urethral stricture, and vitiligo.

 

Interventions

The therapy being considered is platelet rich plasma (PRP) injections.

 

The use of PRP injections has been proposed as a treatment of various non-orthopedic indications and has received considerable interest due to the appeal of a minimally invasive method of applying growth factor for the potential benefit of healing and growth of new structures.

 

Outcomes

The general outcomes of interest are symptoms, changes in disease status, adverse events and  quality of life (QOL).

 

Platelet-Rich Plasma Injection for the Treatment for Androgenetic Alopecia and Alopecia Areata

Androgenetic Alopecia

Androgenetic alopecia is a common form of hair loss in both men and women. In men, this condition is also known as male-pattern baldness. Hair is lost in a well-defined pattern, beginning above both temples. Over time, the hairline recedes to form a characteristic "M" shape. Hair also thins at the crown (near the top of the head), often progressing to partial or complete baldness.

 

The pattern of hair loss in women differs from male-pattern baldness. In women, the hair becomes thinner all over the head, and the hairline does not recede. Androgenetic alopecia in women rarely leads to total baldness.

 

Androgenetic alopecia in men has been associated with several other medical conditions including coronary heart disease and enlargement of the prostate. Additionally, prostate cancer, disorders of insulin resistance (such as diabetes and obesity), and high blood pressure (hypertension) have been related to androgenetic alopecia. In women, this form of hair loss is associated with an increased risk of polycystic ovary syndrome (PCOS). PCOS is characterized by a hormonal imbalance that can lead to irregular menstruation, acne, excess hair elsewhere on the body(hirsutism), and weight gain.

 

Androgenetic alopecia is a frequent cause of hair loss in both men and women. This form of hair loss affects an estimated 50 million men and 30 million women in the United States. Androgenetic alopecia can start as early as a person's teens and risk increases with age; more than 50 percent of men over age 50 have some degree of hair loss. In women, hair loss is most likely after menopause.

 

A variety of genetic and environmental factors likely play a role in causing androgenetic alopecia. Although researchers are studying risk factors that may contribute to this condition, most of these factors remain unknown. Researchers have determined that this form of hair loss is related to hormones called androgens, particularly an androgen called dihydrotestosterone. Androgens also have other important functions in both males and females, such as regulating hair growth.

 

Hair growth begins under the skin in structures called follicles. Each strand of hair normally grows for 2 to 6 years, goes into a resting phase for several months, and then falls out. The cycle starts over when the follicle begins growing a new hair. Increased levels of androgens in hair follicles can lead to a shorter cycle of hair growth and the growth of shorter and thinner strands of hair. Additionally, there is a delay in the growth of new hair to replace strands that are shed.

 

The inheritance pattern of androgenetic alopecia is unclear because many genetic and environmental factors are likely to be involved. This condition tends to cluster in families, however, and having a close relative with patterned hair loss appears to be a risk factor for developing the condition.

 

Treatment for androgenetic alopecia is pharmacologic therapy using 5-alpha reductase inhibitor topical therapy such as minoxidil or systemic agents that inhibit androgen production or action such as oral finasteride. While topical and other pharmacologic therapies are effective, the response to treatment is variable. Treatment may result in no effect, the inhibition of further hair loss, or a variable degree of regrowth of hair. Pharmacologic therapy must be continued indefinitely to maintain the response. Platelet-rich plasma (PRP) injections has emerged as a new treatment modality in the treatment of androgenetic alopecia and is being further investigated due to preliminary evidence suggesting it might have a beneficial role in hair regrowth.

 

In 2018, Cervantes et. al. evaluated the effectiveness of platelet rich plasma treatment for androgenetic alopecia (AGA). A total of 12 studies conducted from 2011 to 2017 were evaluated and summarized by study characteristics, mode of preparation, and treatment protocols. A total of 295 subjects were given PRP or control treatment in studies, and evaluated for terminal hair density, hair quality, andagen/telogen hair ratio, keratinocyte proliferation, blood vessel density, etc. Some studies also provided subject self-assessment reports. Most of the studies reviewed showed effectiveness of PRP in increasing terminal hair density/diameter. However, the authors concluded several study design limitations need to be addressed before PRP is widely introduced as a treatment option in this clinical setting. The field would benefit from additional large scale double-blind, randomized controlled studies treating both men and women, with standardized PRP preparation methods and administration protocol, repeated treatment, standardized objective data documentation and evaluation, physician and subject assessment, isolating the effects of PRP in different grades of AGA, and performing long-term follow-up.

 

In 2018, Giordano et. al. completed a systemic review and meta-analysis on the evidence of platelet-rich plasma (PRP) for androgenetic alopecia (AGA), as there has been an increase in use by plastic surgeons for hair restoration. This meta-analysis compared local injection of PRP versus control to investigate the efficacy of local PRP injections in AGA. The primary outcome was the difference in number of hairs per square centimeter. Secondary outcomes were hair cross-section increase, hair regrowth, and thickness percentage increase. Seven studies were included, five studies were randomized controlled trials (RCTs) and two were retrospective studies. There was a total of 194 patients, age ranged from 19 to 63 years, with a follow up from 3 to 24 months. A significantly locally increased hair number per cm2 was observed after PRP injections versus control (mean difference [MD] 14.38, 95% confidence interval [CI] 6.38-22.38, P < 0.001). Similarly, a significantly increased hair thickness cross-section per 10-4 mm2 (MD 0.22, 95% CI 0.07-0.38, P = 0.005) favoring PRP group. The pooled results did not show a significant percentage increase in hair number (MD 18.79%, 95% CI - 8.50-46.08, P = 0.18), neither hair thickness (MD 32.63%, 95% CI - 16.23-81.48, P = 0.19) among patients treated with PRP. The results of this meta-analysis should be viewed in light of a number of limitations and potential bias influencing these findings. The number of patients considered was extremely small and there were differences in patients’ age, devices used, centrifugation methods, control, and areas of treatment, which might be a confounding factor for the results. Other major limitations of this pooled analyses include the fact that most of the included studies used internal controls, where the patient’s contralateral side or other areas served as its own control, whereas in others, patients were randomized into groups where PRP was either used or not used. There were also differences in the treated scalp areas. The authors concluded, PRP injection for local hair restoration in patients with AGA seems to increase hairs number and thickness with minimal or no collateral effects. However, the current evidence does not support this treatment modality over other treatments due to the lack of clinical evidence, established protocols (i.e., number of sessions, centrifugation, zones to be injected, etc.), and long-term follow-up outcomes. The results of this meta-analysis should be interpreted with caution because it includes pooling many small studies and larger randomized studies should be performed to verify this perception. The medical literature does not confirm that the treatment is scientifically relevant. The addition of PRP might be useful in improving the outcomes of hair transplantation procedures, but there is no evidence whether PRP is more effective then minoxidil or finasteride treatments. Larger studies with long-term follow-up are warranted to validate this promising treatment modality.

 

Alopecia Areata

Alopecia areata is a common disorder that causes hair loss. "Alopecia" is a Latin term that means baldness, and "areata" refers to the patchy nature of the hair loss that is typically seen with this condition.

 

In most people with alopecia areata, hair falls out in small, round patches, leaving coin-sized areas of bare skin. This patchy hair loss occurs most often on the scalp but can affect other parts of the body as well. Uncommonly, the hair loss involves the entire scalp (in which case the condition is known as alopecia totalis) or the whole body (alopecia universalis). Other rare forms of alopecia areata, which have different patterns of hair loss, have also been reported.

 

Alopecia areata affects people of all ages, although it most commonly appears in adolescence or early adulthood. Hair loss occurs over a period of weeks. The hair usually grows back after several months, although it may fall out again. In some cases, unpredictable cycles of hair loss followed by regrowth can last for years. In addition to hair loss, some affected individuals have fingernail and toenail abnormalities, such as pits on the surface of the nails.

 

The hair loss associated with alopecia areata is not painful or disabling. However, it causes changes in a person's appearance that can profoundly affect quality of life and self-esteem. In some people, the condition can lead to depression, anxiety, and other emotional or psychological issues.

 

Alopecia areata affects 1 in every 500 to 1,000 people in the United States. It is one of many recognized forms of alopecia; alopecia areata is the second most common form after androgenetic alopecia (male-pattern baldness in men and female-pattern baldness in women). Alopecia areata affects men and women equally, and it can occur in people of any ethnic background.

 

Alopecia areata is one of a large group of immune system diseases classified as autoimmune disorders. Normally, the immune system protects the body from foreign invaders, such as bacteria and viruses, by recognizing and attacking these invaders and clearing them from the body. In autoimmune disorders, the immune system malfunctions and attacks the body's own tissues instead. For reasons that are unclear, in alopecia areata the immune system targets hair follicles, stopping hair growth. However, the condition does not permanently damage the follicles, which is why hair may later regrow.

 

Many of the genes that have been associated with alopecia areata participate in the body's immune response. These include several genes belonging to a gene family called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders. Each HLA gene has many different variations, allowing each person's immune system to react to a wide range of foreign proteins. Certain variations in HLA genes likely contribute to the inappropriate immune response targeting hair follicles that leads to alopecia areata. Immune system genes outside the HLA complex, such as several genes involved in inflammation, have also been associated with alopecia areata.

 

Some of the genetic variations associated with alopecia areata have been identified in people with other autoimmune disorders, which suggests that this group of diseases may share some genetic risk factors. People with alopecia areata have an increased risk of developing other autoimmune disorders, including vitiligo, systemic lupus erythematosus, atopic dermatitis, allergic asthma, and autoimmune thyroid diseases (such as Hashimoto thyroiditis and Graves disease). Similarly, people with those autoimmune disorders have an increased risk of developing alopecia areata.

 

In many cases, it is unknown what triggers hair loss in people with alopecia areata. It is possible that environmental factors, such as emotional stress, physical injury, or illness, provoke an abnormal immune response in people who are at risk. However, in most affected people, the onset of hair loss has no clear explanation.

 

The inheritance pattern of alopecia areata is unclear because multiple genetic and environmental factors appear to be involved. Overall, the risk of developing the condition is greater for first-degree relatives (such as siblings or children) of affected individuals than it is in the general population. People with alopecia areata are also more likely to have family members with other autoimmune disorders.

 

Treatment success depends on the age of onset and the extent of hair loss. The prognosis tends to be worse in more extensive cases (alopecia totalis or universalis), or when alopecia areata begins in early childhood. The most common treatment for mild cases of alopecia areata (involving less than 50% of loss of scalp hair) is direct intradermal injections of corticosteroids into patches of hair loss. Multiple injections are administered monthly to the skin in and around the bare patches; an average of 4 to 6 monthly injections are usually required for significant improvement. Therapy for extensive alopecia areata (involving more than 50% loss of scalp hair) may be prolonged and difficult but consists of topical immunotherapy. Systematic corticosteroids may be required depending on the severity of the condition and the adequacy of the response to topical therapy. Platelet-rich plasma (PRP) injections has emerged as a new treatment modality in the treatment of alopecia areata and is being further investigated due to preliminary evidence suggesting it might have a beneficial role in hair regrowth.

 

In 2013, Trink et. al. performed a randomized, double-blind, placebo and active controlled, half-head study to evaluate the effects of platelet-rich plasma (PRP) on alopecia areata (AA). Alopecia areata (AA) is a common autoimmune condition, causing inflammation-induced hair loss. This disease has very limited treatment possibilities, and no treatment is either curative or preventive. Platelet-rich plasma (PRP) has emerged as a new treatment modality in dermatology, and preliminary evidence has suggested that it might have a beneficial role in hair growth. Forty-five patients with AA were randomized to receive intralesional injections of PRP, triamcinolone acetonide (TrA) or placebo on one half of their scalp. The other half was not treated. Three treatments were given for each patient, with intervals of 1 month. The endpoints were hair regrowth, hair dystrophy as measured by dermoscopy, burning or itching sensation, and cell proliferation as measured by Ki-67 evaluation. Patients were followed for 1 year. PRP was found to increase hair regrowth significantly and to decrease hair dystrophy and burning or itching sensation compared with TrA or placebo. Ki-67 levels, which served as markers for cell proliferation, were significantly higher with PRP. No side-effects were noted during treatment. The authors concluded, this pilot study, which is the first to investigate the effects of PRP on AA, suggests that PRP may serve as a safe and effective treatment option in AA, and calls for more extensive controlled studies with this method.

 

In 2017, Alyatollahi et. al. conducted a systematic review of the literature regarding the treatment of non-scarring hair loss with platelet-rich plasma (PRP) treatment. Although there are many studies showing the role of platelet rich plasma (PRP) in bone grafts, teeth osteosynthesis, and wound healing, there have been little peer reviewed studies about the safety and efficacy of PRP application in the treatment of hair loss. Among 704 articles, 18 articles matched the inclusion criteria, 14 for androgenic alopecia and four for alopecia areata. They included two case reports, eight case series, six controlled clinical trials and only two randomized controlled trials. The authors concluded, most of the available evidence has shown low quality and controversial results about the efficacy of PRP in treating non-cicatricial alopecias, including androgenetic alopecia and alopecia areata. Further randomized controlled studies with more sample size and standard protocols regarding the number and interval of treatment sessions, number of platelets, method of activation, etc., are required to investigate the efficacy and safety of PRP in treating hair loss.

 

Summary of Evidence

Despite the growing interest in regenerative medicine, few trials investigating platelet-rich plasma (PRP) efficacy on hair growth has been published. Most of the reviewed studies have important methodological deficiencies. Main flaws include lack of a reference protocol regarding the frequency of applications as well as the injected amount of PRP, heterogeneity in application modes, lack of controls, small sample size, lack of detailed reports in patients’ characteristics and used statistical methods. Furthermore, few studies referred to the safety profile of PRP. In addition, currently there is no evidence that PRP is more effective than minoxidil or finasteride treatments. Additional large scale double-blind, randomized controlled studies treating both men and women, with standardized PRP preparation methods and administration protocols, repeated treatments, standardized objective data documentation and evaluation, physician and subject assessment, isolating the effects of PRP in different grades of androgenetic alopecia and alopecia areata, and performing long-term follow-up. The evidence is insufficient to determine the effects of the technology on net health outcomes.

 

Platelet-Rich Plasma Injection for the Treatment of Vitiligo

Vitiligo is a disease that causes the loss of skin color in blotches. Usually the discoloration first shows on sun-exposed areas, such as the hands, feet, arms, face and lips. The extent and rate of color loss from vitiligo is unpredictable. It can affect the skin on any part of the body. Normally the color of hair and skin is determined by melanin. Vitiligo occurs when the cells that produce melanin die or stop functioning. Vitiligo affects people of all skin types, but it may be noticeable in people with darker skin. Vitiligo can start at any age, but often appears before the age of 20. Treatment for vitiligo may restore color to the affected skin, but it does not prevent continued loss of skin color or recurrence.  The use of platelet-rich plasma (PRP) is receiving interest as potential treatment of several dermatological diseases, including vitiligo.

 

In 2019, Hesseler et. al. stated that the field of dermatology has seen numerous therapeutic innovations in the past 10 years with platelet-rich plasma (PRP), recently garnering interest in alopecia, acne scarring, and skin rejuvenation. In other conditions of dermatology, such as chronic wounds and vitiligo, PRP has been examined but has received less attention. A systematic review was conducted that focused on conditions of medical dermatology and consolidated the available evidence on PRP for the practicing dermatologist. They evaluated the literature up to October 31, 2018 and search was conducted in the PubMed database for  "platelet-rich plasma," "platelet releasate," "platelet gel," "platelet-rich fibrin" or "PRP" and "dermatology," "skin," "cutaneous," "wound," or "ulcer." In total, 14 articles met the inclusion criteria for this review. In studies representing Levels of Evidence 1b-4 according to the Center for Evidence-Based Medicine, Oxford, PRP significantly improved wound healing in chronic diabetic ulcers, venous ulcers, pressure ulcers, leprosy ulcers, acute traumatic wounds, and ulcers of multifactorial etiologies; two studies also documented benefits of adjunctive PRP in stable vitiligo. The authors concluded that in vitiligo as well as chronic wounds of multiple etiologies, PRP warrants further investigation because it represents a potential therapeutic adjunct or alternative with a favorable side effect profile.

 

In 2020, Merucri et. al. conducted a review with the aim to identify studies that documented the use of platelet – rich plasma (PRP) for vitiligo. Six studies were identified with a total of 253 patients. The mean time of follow-up of treated patients was 6 months (ranging between 3 and 12 months). In all reports, all treated patients showed a stable vitiligo, and a significantly higher improvement in the PRP groups was always observed compared to control groups, regardless of the combined treatment associated with PRP. Regarding the side effects, PRP in vitiligo patients is safe, without important and specific side effects. Pain at the injection site was the main side effect, although it can be avoided applying 45–60 minutes before the injection of an anesthetic cream. In order to avoid local superinfection topical antibiotics can be used 3 days after injection. Ecchymosis in the site of injection may occur. Ejjiyar et. al. reported the onset of Koebner’s phenomenon in a female patient phototype IV with the onset of facial non-segmental vitiligo after the third injection of PRP, for aesthetic purposes. The authors concluded PRP is a well-tolerated agent, recently receiving increasing attention by the medical community for its potential use in several dermatological conditions, including vitiligo. Literature confirms PRP as a safe and promising treatment for stable vitiligo lesions in different body sites, above all when PRP is combined with other physical procedures, such as fractional carbon dioxide laser. Four-six sessions, with 2–3-week interval are needed in order to obtain clinically significant results. However, the lack of consensus regarding preparation methods, makes it difficult to compare results from different clinical studies. Larger clinical trials with longer time of observation and the standardization of processing protocols represent a very fertile field for future research about the effectiveness of PRP for the treatment of vitiligo.

 

Summary of Evidence

Based on review of the peer reviewed medical literature, there is limited evidence regarding the use of platelet-rich plasma (PRP) injections in the treatment of vitiligo. While these studies may have shown promise, to date, no standard protocols regarding PRP preparation exist.  Published studies report variations in processing, such as the number of centrifugations or compounds added, which make it difficult to compare results from different clinical studies.  The use of PRP for the treatment of vitiligo warrants further investigation in well-designed randomized comparative studies with longer time of observaton to determine its efficacy. The evidence is insufficient to determine the effects of the technology on net health outcomes.

 

Platelet-Rich Plasma Injection for the Treatment of Cerebral Palsy

In 2015, Alcaraz et. al. reported on case of a cerebral palsy (CP) patient who received intravenous platelet-rich plasma (PRP). These investigators administered an intravenous injection of concentrated PRP (25 cc) in a 6 -year- old boy with perinatal CP, cognitive impairment, and marked and severe generalized spasticity. They performed follow-up at 3 and 6 months after the injection. All serum samples for determination were obtained by ELISA technique. Cognitive scales (Bayley, Battelle, M.S.C.A, Kaufman ABC, and Stanford-Binet Intelligence scale) were used before and after treatment. The determination protocol that was applied before the analysis was performed manually and the autotransfusion was considered suitable for treatment. These researchers determined the plasma levels of factor similar to insulin-1 (IGF-1), platelet-derived growth factor (PDGF), vasculo-endothelial growth factor (VEGF), and transforming growth factor B (TGF-B) before and during treatment monitoring. No adverse effects were observed in the patient except for a small hematoma in the area channeling venous access. These investigators observed a clear improvement in the cognitive sphere (memory, ability to perform more complex tasks, and acquisition of new skills) and in language, maintaining stable levels of growth factor in plasma 3-5 times higher than average for his age group at both 3- and 6-month follow-up. Positron emission tomography (PET) images showed an evident increased demarcation in the cerebral cortex. The authors proposed that this therapy is useful in these patients to harness the neurostimulative and neuroregenerative power of endogenous growth factors derived from platelets. The findings of this single case study need to be validated in well-designed randomized studies.

 

Summary of Evidence

Based on review of the peer reviewed medical literature, there is little evidence (one case study) regarding the use of platelet-rich plasma (PRP) injections in the treatment of cerebral palsy (CP). While this study may have shown some promise, to date, no standard protocols regarding PRP preparation exist. Published studies report variations in processing, such as the number of centrifugations or compounds added, which make it difficult to compare results from different clinical studies.  The use of PRP for the treatment of cerebral palsy (CP) warrants further investigation in well-designed randomized comparative studies to determine its efficacy. The evidence is insufficient to determine the effects of the technology on net health outcomes.

 

Platelet-Rich Plasma Injection for the Treatment of Crohn’s Disease-Related Perianal Fistula

In 2015, Gottgens et. al. conducted a prospective pilot study in one tertiary referral center in the attempt to improve healing rates by combining the well-known mucosal advancement flap with platelet-rich plasma (PRP). Consecutive patients with primary or recurrent Crohn's disease-related high perianal fistulas, defined as involving the middle and/or upper third parts of the anal sphincter complex, were included. A staged procedure was performed with non-cutting seton treatment for 3 months first, followed by a mucosal advancement flap with injection of platelet-rich plasma into the fistula tract. Ten consecutive patients were operated on between 2009 and 2014. Half (50%) of the patients had undergone previous fistula surgery. Mean follow-up was 23.3 months (SD 13.0). Healing of the fistula was 70% (95% confidence interval, 33-89%) at 1 year. One patient (10%) had a recurrence, and in two patients (20%) the fistula was persistent after treatment. An abscess occurred in one patient (10%). The median post-operative Vaizey score was 8.0 (range 0-21), indicating a moderate to severe continence impairment. The authors concluded, the results of combining the mucosal advancement flap with platelet-rich plasma (PRP) in patients with Crohn’s disease-related high perianal fistulas are moderate with a healing rate of 70%. Further investigation is needed to determine the benefits and risks on continence status for this technique in this patient population.

 

Summary of Evidence

Based on review of the peer reviewed medical literature, there is little evidence (one prospective pilot study) on combining the well-known mucosal advancement flap with platelet-rich plasma (PRP) in the treatment of Crohn's disease-related high perianal fistulas. While this study may have shown some promise, to date, no standard protocols regarding PRP preparation exist. Published studies report variations in processing, such as the number of centrifugations or compounds added, which make it difficult to compare results from different clinical studies. The use of PRP in the treatment of Crohn's disease-related high perianal fistulas warrants further investigation in well-designed randomized comparative studies to determine its efficacy. The evidence is insufficient to determine the effects of the technology on net health outcomes.

 

Platelet-Rich Plasma Injection for the Treatment of Urethral Stricture

In 2016, Gul reported on the use of a modified platelet-rich plasma with a transforming growth factor B1 neutralization antibody injection that may reduce the recurrence rate of urethral stricture. Urethral stricture is one of the most bothersome urologic disease among urologists and has a substantial impact on quality of life and healthcare costs. Although it can be cured with internal urethrotomy easily, post-surgery stricture recurrence is challenging. Several adjuvant therapies have been used in conjunction with internal urethrotomy but none of them are used routinely because the pathophysiology of the disease is still obscure. Fibrosis is the most accused hypothesis for the action. Platelet-rich plasma (PRP) is an autologous blood product containing a high concentration of platelets that is being used for a very wide range of clinical healing applications. It comprises a concentration of fundamental protein growth factors shown to be actively excreted by platelets to initiate accurate wound healing. Although PRP can play a critical role in wound healing and has been used in fibrotic diseases successfully, it has some deleterious cytokines such as transforming growth factor β1 (TGF β1) which can also cause fibrosis. The author concluded, that the new hypothesis is that the subcutaneous injection of neutralized platelet-rich plasma with TGFβ1 antibody at the planned urethrotomy site may prevent recurrence and provide superior healing and long-term results. This theory needs to be validated in well-designed randomized studies.

 

Summary of Evidence

Based on review of the peer reviewed medical literature, there were no studies found regarding the use of platelet rich plasma injections for the treatment of urethral stricture. The above noted study is a hypothesis regarding this treatment. Further investigation in well-designed randomized comparative studies is needed regarding the use of platelet-rich plasma injections for the treatment of urethral stricture to determine its efficacy. To date, no standard protocols regarding PRP preparation exist. Published studies report variations in processing, such as the number of centrifugations or compounds added, which make it difficult to compare results from different clinical studies. The evidence is insufficient to determine the effects of the technology on net health outcomes.

 

Practice Guideline and Position Statements

There is no evidence based clinical practice guidelines that recommend the use of platelet-rich plasma (PRP) injections in the treatment of non-orthopedic indications to include the use in dermatological diseases.

 

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.

 

A number of PRP preparation systems are available, many of which were cleared for marketing by FDA through the 510(k) process for producing platelet-rich preparations intended to be mixed with bone graft materials to enhance the bone grafting properties in orthopedic practices. The use of PRP outside of this setting (e.g., an office injection) would be considered off-label.

 

Examples of approved devices include:

  • Aurix™ System (Nuo Therapeutics, Inc. Gaithersburg, MD)
  • AutoloGel (Cytomedix, Inc., Rockville, MD)
  • Autologous Platelet Grafting™ (SafeBlood® Technologies, Inc., Little Rock, AR)
  • Cascade® Autologous Platelet System (Musculoskeletal Transplant Foundation [MTF], Edison, NJ)\
  • Fibrinet® Autologous PRP System (Cascade Medical Enterprises, Wayne, NJ)
  • Gravitational Platelet Separation System (GPS®II) (Biomet Biologics, Inc., Warsaw, IN)
  • Mini GPSII (Biomet Biologics, Inc., Warsaw, IN)
  • Elmd-500 Autotransfusion System (Medtronic Electomedics)
  • SmartPReP® 2 APC+ system (Harvest Technologies Corporation, Plymouth, MA)

 

The use of different devices and procedures can lead to variable concentrations of activated platelets and associated proteins, increasing variability between studies of clinical efficacy.

 

Prior Approval:

Not applicable

 

Policy:

See Related Medical Policies

  • 02.01.18 Prolotherapy 
  • 02.01.32 Platelet-Rich Plasma and Autologous Protein Solution for Orthopedic Applications
  • 08.01.22 Stem Cell Therapy for Orthopedic Indications (Including Allograft Bone Products used with Stem Cells)

 

The use of platelet-rich plasma (PRP) injections for the treatment of non-orthopedic indications is considered investigational, to include, but not limited to the following because the effectiveness cannot be established by published peer-reviewed literature:

  • Alopecia areata/androgenetic alopecia
  • Vitiligo
  • Cerebral Palsy (CP)
  • Crohn’s Disease-Related Perianal Fistula
  • Urethral stricture

 

Procedure Codes and Billing Guidelines:

To report provider services, use appropriate CPT* codes, Alpha Numeric (HCPCS level 2) codes, Revenue codes and / or diagnosis codes.

  • 0232T Injection(s), platelet rich plasma, any tissue, including image guidance, harvesting and preparation when performed

 

Selected References:

  • UpToDate: Alopecia Areata: Management. Andrew G. Messenger M.D., FRCP. Topic last updated September 9, 2019.
  • UpToDate. Female Pattern Hair Loss (Androgenetic Alopecia in Women): Treatment and Prognosis. Amy McMichael M.D., Topic last updated September 26, 2019.
  • UpToDate. Treatment of Androgenetic Alopecia in Men. Jeff Donovan M.D., PhD, Beth G. Goldstein M.D., Adam O. Goldstein M.D., MPH. Topic last updated February 27, 2019.
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  • Garg S, Messenger AG. Alopecia areata: evidence- based treatments. Semin Cutan Med Surg 2009 Mar;28(1):15-8. PMID 19341938
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Policy History:

  • November 2020 - Annual Review, Policy Revised
  • November 2019 - New Policy Created

Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc.   They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.

 

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