Platelet Rich Plasma

Title XVIII of the Social Security Act, Section 1862(a)(1)(A) allows coverage and payment for only those services that are considered to be reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member.

Title XVIII of the Social Security Act, Section 1862(a)(1)(D) addresses services that are determined to be investigational or experimental.

CMS Internet-Only Manual, Pub. 100-02, Medicare Benefit Policy Manual, Chapter 16, Section 10 General Exclusions from Coverage

CMS Internet-Only Manual, Pub. 100-03, Medicare National Coverage Determinations (NCD) Manual, Chapter 1, Part 4, Section 270.3 Blood -Derived Products for Chronic Non-healing Wounds. Effective August 2, 2012, upon reconsideration, the Centers for Medicare and Medicaid Services (CMS) has determined that platelet-rich plasma (PRP) – an autologous blood-derived product, will be covered only for the treatment of chronic non-healing diabetic, venous and/or pressure wounds and only when the conditions outlined in the NCD for CED are met.

CMS Internet-Only Manual, Pub. 100-04, Medicare Claims Processing Manual, Chapter 23, Section 30A Physician’s Services

CMS Internet-Only Manual, Pub. 100-04, Medicare Claims Processing Manual, Chapter 30, Section 50.3.1 Mandatory ABN Uses

This is a NON-coverage policy for all platelet rich plasma injections and/or applications as a means of managing musculoskeletal injuries and/or joint conditions.

Introduction

Platelet-rich plasma (PRP) is defined as a platelet-rich concentrate with platelet levels greater than the baseline platelet count in whole blood. This autologous derived substance, also referred to as autologous platelet-derived growth factors, platelet gel, platelet-rich concentrate, autogenous platelet gel, plasma rich in growth factors or platelet releasate, has been proposed for the treatment of multiple conditions to enhance healing. Theoretically, these growth factors function as a mitogen for fibroblasts, smooth muscle cells, osteoblasts and vascular endothelial growth factors.^1,2 While PRP may work by activating the innate immune response and stimulating tissue anabolism, its precise mechanism of action is still unclear.² The role that white blood cells may play is particularly unclear, as the immune cells may act as antimicrobial and/or proinflammatory agents. Furthermore, PRP preparations are not standardized and exhibit wide variability in platelet and white blood cell concentrations and the use of thrombin activators. The way in which variations in PRP composition may impact clinical outcomes is also unclear.³ Mishra et al.⁴ proposed classifying these types in three categories: the presence of white blood cells (e.g., leukocyte-rich or -poor), whether the PRP is activated or not, and the concentration of platelets.

A number of factors have contributed to the growing popularity of biologic therapies despite the dearth of high-quality clinical trials supporting their use. Musculoskeletal conditions are both serious and prevalent. Conventional treatment, for the most part, is lacking in success. Platelet-rich plasma has the appeal of a simple, minimally invasive treatment with little regulation, which can be easily administered via local injection by clinicians. In addition, the biotechnology companies that manufacture the equipment used to assist in the production of these therapies have conducted nation-wide marketing directly to clinicians and consumers, touting success with high profile professional athletes.

A collection and preparation system is used to collect a small sample of blood at the patient’s point of care or clinical laboratory. The systems used for preparing autologous platelet-derived growth factors are Federal Drug Administration (FDA) approved under the 510(k) process. While the technology to obtain PRP is FDA-approved, PRP itself is currently not indicated for direct injection. Centrifugation of this blood sample separates the denser red cells from the plasma. The plasma components are divided into a buffy coat and an adjacent layer. The buffy coat contains leucocytes and most of the platelets. The adjacent layer of plasma is less rich in platelets and has few leucocytes.⁵

There are a variety of techniques used to harvest the buffy coat, the adjacent plasma layer, or both. Some methods concentrate the buffy coat further using a "double spin" technique. This process involves a second centrifugation of the supernatant obtained from the initial centrifugation and produces a more concentrated sample. Depending on the method used, the number of platelets in PRP varies between one and nine times that of whole blood. Techniques that produce higher platelet concentrations (e.g., double spin) typically produce higher leucocyte concentrations as well. Hence, PRP is often referred to as leucocyte rich (LR-PRP) or leucocyte poor (LP-PRP).⁶ 

Some practitioners add exogenous calcium salts to the PRP just prior to administration with the intention of ensuring platelet activation, while others assume that contact with tendon collagen will suffice.⁷ PRP composition can also differ by donor age, health status, gender and even time of day when collected.⁸

Administration protocols also vary per type of injury. PRP may be injected using a peppering technique, whereby the PRP is injected with several penetrations of the tendon from a single skin penetration⁹ or may be injected directly into a joint. Frequency of injections also vary. For tendon conditions, one to four intratendinous injections are given over 2 weeks. Joint conditions typically have three injections given within a 6-month time frame, usually performed 3-4 weeks apart.¹⁰ A local anesthetic is often utilized, and an ultrasound (US) may provide guidance. Local anesthetics may compromise the efficacy of the PRP.¹¹ Patients need to refrain from non-steroidal anti-inflammatory medications for 2 weeks prior to harvesting due to the effect on platelet function.¹² There are no accepted exercise protocols or return-to-sport guidelines following PRP treatment. The usage of PRP can be broadly separated into three categories which will be discussed further: primary treatment for tendinopathies/non-tendon inflammation, surgical augmentation of repairs and primary treatment for osteoarthritis.

Primary Treatment for Tendinopathies/Non-Tendon Inflammation

The evidence regarding PRP treatment of tendinopathies/non-tendon inflammation includes multiple randomized control trials (RCT), as well as systematic reviews with meta-analyses (SR/MA). Typical outcomes are pain relief and functional status. The literature is clustered around usage for the following: lateral epicondylitis (LE), carpal tunnel syndrome (CTS), rotator cuff (RC) tears, plantar fasciitis (PF), achilles tendinopathy (AT), and patellar tendinopathy (PT).

Andia² conducted a review of over 1500 patients treated with PRP for tendinopathies in 58 studies, evenly distributed between lower and upper extremities. Six of these were of Level 1 Evidence Quality, mostly utilizing LR-PRP. Given the heterogeneity in tendinopathies and preparation of PRP, they concluded the data was insufficient to make a recommendation for treatment.

A 2014 systematic review of 19 randomized and quasi-randomized trials of PRP for musculoskeletal soft tissue injuries, involving 1088 participants, noted no difference in clinically important outcomes.¹³ The quality of these studies was limited by small numbers of participants, non-standardization of treatment preparation and outcome measures that focused on subjective pain scores, rather than more objective measures of tendon tissue healing or improvement in function. Additional limitations were lack of accounting for other confounding factors, such as differentiation between an overuse injury vs. degenerative tendon rupture, and whether or not bursal involvement was present. As previously stated, the role of leukocytes in tendon healing is controversial, but the few randomized trials that differentiated between LR-PRP and LP-PRP suggest that LR-PRP may be more effective in treatment of tendinopathies.¹⁴ The evidence, examined in detail below, is insufficient to determine the benefit of PRP on health outcomes for tendinopathies/non-tendon inflammation.

Lateral epicondylitis

Lateral epicondylitis (LE), commonly known as “tennis elbow”, affects approximately 1-3% of the population with men and women equally represented. An overuse injury is characterized by angiofibroblastic hyperplasia.¹⁵ Patients typically complain of pain for 6-12 weeks, but in some cases pain can persist for up to 2 years. Eighty percent recover with no treatment.¹⁶ Although self-limiting, this condition still results in disability, lost productivity and health care utilization costs. Conservative efforts include non-steroidal anti-inflammatory drugs, orthotic devices, physical therapy, glucocorticoid injection and extracorporeal shock wave therapy.

The Washington State Health Care Authority¹⁷ recently published a comprehensive health technology assessment, in which they examined the efficacy and safety of PRP when used in the patient with recalcitrant LE (> 6 months duration). The authors included five RCTs that compared PRP with corticosteroid injection (CS)^18-22 and two RCTs that compared PRP with anesthetic.^9,23 In the short term, neither CS nor local anesthetic differed from PRP regarding pain or function. While in the intermediate term, low quality evidence suggested PRP was superior to CS (P = 0.007) for pain and function, but not local anesthetic (P = 0.08). In the long term, low quality evidence suggested PRP and CS were not different (P = 0.11), but PRP was superior to local anesthetic (P < 0.00001).

Stratification of systematic review/meta-analysis (SR/MA) of eight randomized controlled trials (RCT) by Mi et al.²⁴ found that treatment with PRP appeared to be more effective than CS at intermediate term (12 weeks) and long term (6 months and 1 year) intervals, whereas CS demonstrated superiority in the short term (2-8 weeks).

Montalvan et al.²⁵ conducted a RCT, which found that two US guided PRP injections in 25 patients were no more efficacious than saline injections at 6 and 12 months on either pain score reduction or functional improvement. Mishra et al.⁹ conducted a RCT of 112 patients with LE comparing LR-PRP and bupivacaine injections, concluding there were no differences in global pain scores at 12 weeks. Schoffl found no significant difference between PRP vs. saline in functional improvement at 3 months in a double-blinded (DB) RCT of 50 patients.²⁶

Linnanmaki et al.²⁷ performed a parallel group, randomized, controlled participant- and assessor-blinded study including adults with clinically diagnosed LE. The participants were recruited from a secondary referral center, after not responding to initial nonoperative treatment. One hundred nineteen participants were randomized to receive PRP, saline or autologous blood. Follow-up visits were at 4, 8, 12, 26, and 52 weeks after the injection. The primary outcome measure was improvement in pain, measured with Visual Analog Scale (VAS) in a 0-10 range, without specification as to whether the pain was activity related or at rest, from baseline to 52 weeks. The secondary outcomes were the Disabilities of the Arm, Shoulder and Hand (DASH) score. There were no clinically important differences in the mean VAS pain or DASH scores among the groups at any timepoint. Level of evidence Level II therapeutic study.

One small study looked at PRP as an alternative to operative management. Mayo Clinic²⁸ conducted a non-randomized trial where 15 patients were treated with a series of two LR-PRP injections, and 18 patients were treated with surgery. Outcome measures included time to pain-free status, time to full range of motion (ROM), the Mayo Elbow Performance Score (MEPS), and the Oxford Elbow Score (OES). Successful outcomes were observed in 80% of patients treated with PRP and 94% of those treated operatively (P = 0.37). A statistically significant improvement was noted in both time to full ROM (42.3 days for PRP vs. 96.1 days for surgery; P < .01) and time to pain-free status (56.2 days for PRP vs. 108.0 days for surgery; P < 0.01). No significant difference was found in return-to-activity rates, overall successful outcomes, MEPS scores, or OES scores.

Overall, the current evidence suggests that PRP may yield some long-term benefits that are not apparent before 6 months, particularly when compared with CS. However, analysis of the quality of evidence is limited by sample size too small to be sufficiently powered and lack of correction for multiple comparisons.

Carpal Tunnel Syndrome

Literature reports comparing 5% Dextrose in Water (D5W), CS and PRP injections with non-surgical management of carpal tunnel syndrome (CTS) were systematically reviewed by Lin et al.²⁹ Ten studies with 497 patients comparing five treatments (D5W, PRP, splinting, CS, and normal saline (NS)) were included. The main outcome was the standardized mean difference (SMD) of the symptom severity and functional status scales of the Boston Carpal Tunnel Syndrome Questionnaire at 3 months after injections. The results showed that D5W injection was likely to be the best treatment, followed by PRP injection, in terms of clinical effectiveness in providing symptom relief. With respect to functional improvement, splinting ranked higher than PRP and D5W injections. Lastly, CS and saline injections were consistently ranked fourth and fifth in terms of therapeutic effects on symptom severity and functional status. D5W and PRP injections are more effective than splinting and corticosteroid or saline injection for relieving the symptoms of CTS. Compared with splinting, D5W and PRP injections do not provide better functional recovery.²⁹

In 2009, the UK National Institute for Health and Clinical Excellence (NICE) stated that current evidence on the safety and efficacy of PRP for tendinopathy is inadequate in quantity and quality (NICE 2013). This was reiterated in recent systematic reviews of the evidence.³⁰

Rotator Cuff Tears

Rotator cuff (RC) tears are a common clinical problem in the geriatric population with rates as high as 80% in those over age 80,³¹ and debate exists over how to best provide pain relief and restore shoulder function. Treatment options can be broadly divided into non-surgical and surgical, with the majority of patients initially placed on a trial of conservative therapy. A major concern with RC repairs in older patients is decreased vascularity and healing potential of the tendons. With poorer healing, there is an increased risk of re-rupture, and older age is associated with higher rates of failure following repair. For those with irreparable RC tears, low functional demand, or interest in nonoperative management, there are a number of non-surgical treatments to consider, including rehabilitation and injections of CS, hyaluronic acid (HA) and PRP.

Several meta-analyses have been published, but none have focused exclusively on level 1 RCTs until Chen’s work.³² Eighteen Level I studies were evaluated. The VAS scores were significantly improved short term (-0.45 [95% CI, -0.75 to -0.15]; P < 0.01). Sugaya grade IV and V retears in PRP-treated patients were significantly reduced long term (odds ratio [OR], 0.34 [95% CI, 0.20-0.57]; P < 0.01). In PRP-treated patients with multiple tendons torn, there were reduced odds of retears (OR, 0.28 [95% CI, 0.13-0.60]; P < 0.01). Long-term odds of retears were decreased, regardless of leukocyte content (LP-PRP: OR, 0.36 [95% CI, 0.16-0.82]; LR-PRP: OR, 0.32 [95% CI, 0.16-0.65]; all P < 0.05) or usage of gel (non-gel: OR, 0.42 [95% CI, 0.23-0.76]; gel: OR, 0.17 [95% CI, 0.05-0.51]; all P < 0.01). The conclusion was that long-term retear rates were significantly decreased in patients with rotator cuff-related abnormalities who received PRP. Significant improvements in PRP-treated patients were noted for multiple functional outcomes, but none reached their respective minimal clinically important differences. Overall, the results suggest that PRP may positively affect clinical outcomes, but limited data, study heterogeneity, and poor methodological quality hinder firm conclusions.

In their double-blind, RCT of 40 patients (average age 51) with RC tears, Kesikburun et al.³³ randomized patients to a single 5-mL injection of either PRP or saline, in addition to a standard 6-week exercise program. At 1-year follow-up, the authors found that PRP was no better than placebo at improving quality of life, pain, disability, and shoulder ROM. In contrast, positive results were reported by Rha et al.³⁴ in their study of 39 patients (average age 45) with tendinosis or partial RC tears. Patients were randomized to either two injections of PRP or dry needling spaced 4 weeks apart. At the 6-month follow-up, those treated with PRP had superior results in terms of pain, function, and ROM.

Plantar Fasciitis

Singh et al.³⁵ conducted a SR/MA study comparing PRP injections and CS injections for plantar fasciopathy (PF). Studies were assessed using the Cochrane Risk of Bias Tool and the Newcastle Ottawa Scale (NOS). The primary endpoint was pain and function score at 3- and 6-month follow-up. Ten studies with a total of 517 patients were included. Seven studies were randomized. Studies reported outcomes using the VAS and American Orthopedic Foot and Ankle Score (AOFAS). At 3-month follow-up, PRP injections were associated with improved VAS scores (standard mean difference [SMD], -0.66; 95% CI, -1.3 to -0.02; p = 0.04) and AOFAS scores (SMD, 1.87; 95% CI, 0.16-3.58; p = 0.03). However, by the 6-month follow-up, there was no difference in VAS score (SMD, -0.66; 95% CI, -1.65 to 0.3; p = 0.17) or AOFAS scores (SMD, 1.69; 95% CI, -1.06 to 4.45; p = 0.23).

Sarah Johnson-Lynn et al.³⁶ randomized 28 patients³⁵ with 6 months or more of magnetic resonance imaging (MRI)-proven PF to PRP or saline. Using the VAS, both treatments resulted in a similar, significant improvement in symptoms at 6 months. Levels of Evidence: Level II.

A larger, randomized trial of 115 patients³⁷ compared CS to PRP using Foot Function Index pain score (FFI). In the control group, FFI Pain scores decreased quickly, and then remained stable during follow-up. In the PRP group, FFI Pain reduction was more modest, but reached a lower point after 12 months than the control group. After adjusting for baseline differences, the PRP group showed significantly lower pain scores at the 1-year follow-up than the control group (mean difference, 14.4; 95% CI, 3.2-25.6). The number of patients with at least 25% improvement (FFI Pain score) between baseline and 12-month follow-up differed significantly between the groups. Of the 46 patients in the PRP group, 39 (84.4%) improved at least 25%, while only 20 (55.6%) of the 36 in the control group showed such an improvement (P = 0.003). The PRP group showed significantly lower FFI Disability scores than the control group (mean difference, 12.0; 95% CI, 2.3-21.6).

Achilles Tendinopathy

RCTs of 24 patients with injection of PRP vs. saline into achilles tendinopathy (AT) demonstrated no significant difference at 3 months in Victorian Institute of Sports Assessment-Achilles (VISA-A) score.³⁸ A 1-year follow-up of 54 patients in a similar trial also found no improvement.³⁹

Patellar Tendinopathy

Patellar tendinopathy is a condition characterized by anterior knee activity related pain, most commonly found in athletes who engage in jumping sports. A well-designed multisite single-blind study randomized 57 athletes with patellar tendinopathy to LR-PRP, LP-PRP, and saline ultrasound guided injections. All participants received one injection followed by 6 weeks of supervised rehabilitation training three times per week. Study retention was 93% at 12 weeks and 79% after 1 year. Using the outcome measure, Victorian Institute of Sport Assessment-patellar (VISA-P), there was no significant difference in mean change in VISA-P score, pain, or global rating of change among the three treatment groups at 12 weeks or any other time point.⁴⁰ A SR/MA addressed 70 studies of treatment of patellar tendinopathy involving 2530 patients, reported in 22 studies on eccentric exercise, extracorporeal shockwave therapy (ESWT), and PRP. Eccentric exercise therapies obtained the best results (P < 0.05) at short-term (< 6 months, mean 2.7 +/- 0.7 months). However, multiple injections of PRP obtained the best results (P < 0.05), followed by ESWT and eccentric exercise, at long-term follow-up (>/=6 months, mean 15.1 +/- 11.3 months).⁴¹

A different SR looked at 15 studies comparing eccentric training, PRP, CS and ESWT. Eccentric training, with or without core stabilization or stretching, improved symptoms by 61% in the VISA-P score with a 95% confidence interval. Results from ESWT demonstrated 54% improvement and PRP studies 55% improvement with similar confidence intervals. Finally, CS injection provided no benefit.⁴²

In summary, findings from RCTs and SR/MA have been mixed and have generally found that PRP did not have a statistically and/or clinically significant impact on pain or functional outcomes. In RCTs that have found significantly improved pain outcomes for PRP injections, important relevancy gaps and study conduct limitations preclude reaching strong conclusions based on their findings. The evidence is insufficient to determine the benefit of PRP on health outcomes for patellar tendinopathy.

Surgical Augmentation of Repairs

The majority of RCTs with surgical repair of rotator cuff or Achilles tendon have not demonstrated any clinically significant benefit.^43-46 A MA of eight Level I or Level II studies of rotator cuff surgery comparing preoperative and postoperative risk for retears, as well as, gain in functional outcome showed no statistically significant differences between those treated with PRP and those without such an intervention.⁴⁷ An additional MA of Level II and Level III studies by Saltzman et al.⁴⁸ came to similar conclusions. A Cochrane review by Moraes et al.¹³ on platelet-rich therapies for musculoskeletal soft tissue injuries identified two RCTs and two quasi-randomized studies (total n = 203 patients) specifically on PRP used in conjunction with anterior cruciate ligament (ACL) reconstruction. Pooled data found no significant difference in International Knee Documentation Committee (IKDC) scores between the PRP and control groups. The evidence is insufficient to determine the benefit of PRP on health outcomes for surgical augmentation of repairs.

Primary Treatment for Osteoarthritis

Osteoarthritis (OA) is a common disease involving joint damage, an inadequate healing response and progressive deterioration of the joint architecture. Presently, intra-articular injections of CS or viscosupplementation with HA remain the mainstay of conservative treatment. The evidence for using PRP for this condition includes multiple RCTs and systematic reviews. Most trials have compared PRP with HA for knee osteoarthritis, though HA as a comparator is questionable, because the evidence demonstrating the benefit of HA for osteoarthritis is not robust.

Systematic reviews have generally found that PRP was more effective than placebo or HA in reducing pain and improving function. However, systematic review authors have noted that their findings should be interpreted with caution due to important limitations, including significant statistical heterogeneity, questionable clinical significance, and high risk of bias in study conduct.⁴⁹ One retrospective study compared PRP to HA in 190 patients between January 2014 and October 2017. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), VAS, and ROM were measured before injection, at 15 days, 6 months, 12 months, and at last follow-up. HA treated patients experienced a higher arthroplasty rate (36.0% vs 5.3%, p < 0.001), lower ROM, worse VAS and WOMAC score, and increased risk of any arthroplasty occurrence (log-rank < 0.001) than PRP patients.⁴⁹

A 2014 systematic review of 10 randomized and non-randomized trials of PRP for OA of the knee found intra-articular PRP injections were more effective for pain reduction (mean difference (MD) -2.45; 95% CI -2.92 to -1.98; p value < 0.00001 and MD -2.07; 95% CI -2.59 to -1.55; p value < 0.00001, single and double PRP injections, respectively) compared with placebo at 6 months post injection. Intra-articular PRP injections were compared with hyaluronic acid and showed a statistically significant difference in favor of PRP on pain reduction based on the VAS and numeric rating scale (standardized mean difference -0.92; 95% CI -1.20 to -0.63; p value <0.00001) at 6 months post injection. Almost all trials revealed a high risk of bias.⁵⁰

A similar SR/MA in 2020 of 18 studies (all level 1) met inclusion criteria, including 811 patients undergoing intra-articular injection with PRP (mean age, 57.6 years) and 797 patients with HA (mean age, 59.3 years). The mean follow-up was 11.1 months for both groups. Mean improvement was significantly higher in the PRP group (44.7%) than the HA group (12.6%) for WOMAC total scores (P < 0.01). Of 11 studies based on the VAS, six reported PRP patients to have significantly less pain at latest follow-up when compared with HA patients (P < 0.05). Of six studies based on the Subjective IKDC outcome score, three reported PRP patients to have significantly better scores at latest follow-up when compared with HA patients (P < 0.05). Finally, LP-PRP was associated with significantly better Subjective IKDC scores vs. LP-PRP (P < 0.05).⁵¹

A recent prospective study compared the efficacy of intra-articular injections of PRP and HA with a control group of NS solution for knee OA. This was a randomized, dose-controlled, placebo-controlled, double-blind, triple-parallel clinical trial. A total of 87 osteoarthritic knees (53 patients) were randomly assigned to one of three groups receiving 3 weekly injections of either LP-PRP (31 knees), HA (29 knees), or NS (27 knees). WOMAC score and IKDC subjective score were collected at baseline and at 1, 2, 6, and 12 months after treatment. All three groups showed statistically significant improvements in both outcome measures at 1 month; however, only the PRP group sustained the significant improvement in both the WOMAC score (63.71 ± 20.67, increased by 21%) and IKDC score (49.93 ± 17.74, increased by 40%) at 12 months. The conclusion was that intra-articular injections of LP-PRP can provide clinically significant functional improvement for at least 1 year in patients with mild to moderate OA of the knee.⁵²

However, evidence is still limited due to overall high risk of bias in previous trials and great variability between studies regarding the number of injections (generally one to four), interval between injections, preparation of the PRP, and volume injected. Furthermore, the typical length of follow up was only 1 year or less. There is also uncertainty regarding whether individuals with less severe OA may benefit more from this intervention compared with individuals with more advanced structural damage. Additionally, it is unclear as to whether LR-PRP or LP-PRP should be utilized, though the latter appears to have an advantage. Larger controlled studies comparing PRP with placebo and alternatives other than HA are needed to determine the efficacy of PRP for knee OA. Further studies are also needed to determine the optimal protocol for delivering PRP. At the present time, the evidence is insufficient to determine the effects of PRP on health outcomes for OA.

Primary Treatment for Chronic Low Back Pain

Low back pain (LBP) is now regarded as the first cause of disability worldwide, causing morbidity and socioeconomic loss.⁵³ Conventional treatments include physical therapy, CS injection, medial bundle branch block (MBBB) and surgery. Intervertebral disc (IVD) degeneration is an important pathogenesis of LBP. Several animal studies have shown that the injection of PRP into degenerated IVDs is effective in restoring structural changes (IVD height) and improving the matrix integrity of degenerated IVDs as evaluated by MRI and histology.⁵⁴ Recently, a small number of studies have promoted PRP injection as a relatively safe means of treating patients with degenerative disc disease, who have failed other means of managing their LBP. A small number of prospective trials have suggested there may be some benefit to using PRP injection in the treatment of pain or functional decline caused by facet joint arthropathy.⁵⁵

Forty-seven adults with chronic (≥ 6 months), moderate-to-severe lumbar discogenic pain unresponsive to conservative treatment were randomized to receive intradiscal PRP or contrast agent after provocative diskography. Data on pain, physical function, and participant satisfaction were collected at 1 week, 4 weeks, 8 weeks, 6 months, and 1 year utilizing Functional Rating Index (FRI), Numeric Rating Scale (NRS) for pain, the pain and physical function domains of the 36-item Short Form Health Survey, and the modified North American Spine Society (NASS) Outcome Questionnaire. Over 8 weeks of follow-up, there were statistically significant improvements in the 29 participants who received intradiscal PRP with regards to pain (NRS Best Pain) (P = 0.02), function (FRI) (P = 0.03), and patient satisfaction (NASS Outcome Questionnaire) (P = 0.01) compared with controls.⁵⁶

A non-randomized comparator study by Bise et al.⁵⁷ looked at the efficacy of interlaminar computed tomography (CT) guided epidural PRP and CS injections in 60 patients. Utilizing the NRS and for function with the Oswestry Disability Index (ODI) before and 6 weeks after treatment. At 6 weeks there was found to be no statistical difference between the two groups.

The American Society of Interventional Pain Physicians reviewed the evidence for PRP usage in LBP. They found Level III evidence for intradiscal injections of PRP, whereas the evidence is considered Level IV for lumbar facet joint, lumbar epidural, and sacroiliac joint injections of PRP, (on a scale of Level I through V) using a qualitative modified approach to the grading of evidence based on best evidence synthesis.⁵³ The evidence is insufficient to determine the benefit of PRP on health outcomes for chronic LBP.

The use of autologous biologics to replace or restore damaged tissue is a relatively new area of medicine that has yet to substantiate its oucomes.⁵³ The American Academy of Orthopedic Surgeons (AAOS) announced at its November 2019 meeting that over the next 5 years, it would prioritize research and development for biologics to create evidence-based position statements. Their goals are to establish registries for postmarket monitoring, standardize reporting requirements and clarify by disease state a consensus approach for biological markers and clinical trial design.⁵⁸

PRP is a general term describing a therapy with no gold standard of preparation or administration technique. This heterogeneity and the small number of controlled trials make it difficult to assess the efficacy of PRP for any disorder. There is a lack of standardization of the preparations of PRP amongst the trials, with varying concentration of platelet, frozen vs. fresh preparations, and the filtration of white cells. While the body of evidence of utility for PRP is large, the overall quality of evidence is low. The studies are relatively small, observational studies, often confounded by lack of treatment control, precluding cause-and-effect conclusions. RCTs that compare outcomes in patients whose treatment is standardized are needed to determine definitive patient selection criteria and clinical utility. The lack of level I evidence, no clinical practice guideline endorsement, as well as no commercial coverage, argue strongly against current PRP coverage as reasonable and necessary for treatment of Medicare patients.

While promising, we believe that there is insufficient high-quality evidence to justify the use of PRP for the treatment of any condition except for within the confines of a well-designed clinical trial. Thus, National Government Services considers PRP injection and PRP combined with stem cells for musculoskeletal injuries and/or joint conditions, whether primary or adjunctive use, to be experimental and investigational, because its effectiveness has not been established. PRP therapy is an evolving area of research. Once PRP preparations are standardized, trials can more precisely highlight which factors are associated with better outcomes, yielding more effective PRP preparations and patient selection criteria. National Government Services will continue to monitor scientific developments and may adjust this coverage policy in accordance.

Aetna: Aetna considers PRP injections experimental and investigational for all indications, including LE and elbow tendinopathy, because their effectiveness has not been established.

Blue Cross Blue Shield of South Carolina: The evidence is insufficient to determine the effects of the technology on health outcomes.

CIGNA: Cigna considers the use of autologous platelet-derived growth factors for any condition or indication, including epicondylitis, experimental, investigational, or unproven.

National Institute for Health and Care Excellence (NICE) 2019: Current evidence on PRP injections for knee OA raises no major safety concerns. However, the evidence on efficacy is limited in quality. Therefore, this procedure should only be used with special arrangements for clinical governance, consent, and audit or research.

UnitedHealthcare (UHC): UHC considers PRP (e.g., autologous platelet-derived growth factor) unproven and not medically necessary when used to enhance bone or soft tissue healing.

1. Eppley BL, Woodell JE, Higgins J. Platelet quantification and growth factor analysis from platelet-rich plasma: implications for wound healing. Plastic and reconstructive surgery. 2004;114(6):1502-1508.
2. Andia I, Maffulli N. Muscle and tendon injuries: the role of biological interventions to promote and assist healing and recovery. Arthroscopy. 2015;31(5):999-1015.
3. Fitzpatrick J, Bulsara MK, McCrory PR, Richardson MD, Zheng MH. Analysis of Platelet-Rich Plasma Extraction: Variations in Platelet and Blood Components Between 4 Common Commercial Kits. Orthop J Sports Med. 2017;5(1):2325967116675272.
4. Mishra A, Harmon K, Woodall J, Vieira A. Sports medicine applications of platelet rich plasma. Current pharmaceutical biotechnology. 2012;13(7):1185-1195.
5. Dhurat R, Sukesh M. Principles and Methods of Preparation of Platelet-Rich Plasma: A Review and Author's Perspective. J Cutan Aesthet Surg. 2014;7(4):189-197.
6. Kevy SV, Jacobson MS. Comparison of methods for point of care preparation of autologous platelet gel. The journal of extra-corporeal technology. 2004;36(1):28-35.
7. Castillo TN, Pouliot MA, Kim HJ, Dragoo JL. Comparison of growth factor and platelet concentration from commercial platelet-rich plasma separation systems. Am J Sports Med. 2011;39(2):266-271.
8. Taniguchi Y, Yoshioka T, Sugaya H, et al. Growth factor levels in leukocyte-poor platelet-rich plasma and correlations with donor age, gender, and platelets in the Japanese population. J Exp Orthop. 2019;6(1):4-4.
9. Mishra AK, Skrepnik NV, Edwards SG, et al. Efficacy of platelet-rich plasma for chronic tennis elbow: a double-blind, prospective, multicenter, randomized controlled trial of 230 patients. Am J Sports Med. 2014;42(2):463-471.
10. Campbell KA, Saltzman BM, Mascarenhas R, et al. Does Intra-articular Platelet-Rich Plasma Injection Provide Clinically Superior Outcomes Compared With Other Therapies in the Treatment of Knee Osteoarthritis? A Systematic Review of Overlapping Meta-analyses. Arthroscopy. 2015;31(11):2213-2221.
11. Bausset O, Magalon J, Giraudo L, et al. Impact of local anaesthetics and needle calibres used for painless PRP injections on platelet functionality. Muscles, ligaments and tendons journal. 2014;4(1):18-23.
12. Schippinger G, Prüller F, Divjak M, et al. Autologous Platelet-Rich Plasma Preparations: Influence of Nonsteroidal Anti-inflammatory Drugs on Platelet Function. Orthop J Sports Med. 2015;3(6):2325967115588896.
13. Moraes VY, Lenza M, Tamaoki MJ, Faloppa F, Belloti JC. Platelet-rich therapies for musculoskeletal soft tissue injuries. The Cochrane database of systematic reviews. 2013(12):Cd010071.
14. Fitzpatrick J, Bulsara M, Zheng MH. The Effectiveness of Platelet-Rich Plasma in the Treatment of Tendinopathy: A Meta-analysis of Randomized Controlled Clinical Trials. Am J Sports Med. 2017;45(1):226-233.
15. Nirschl RP, Pettrone FA. Tennis elbow. The surgical treatment of lateral epicondylitis. J Bone Joint Surg Am. 1979;61(6a):832-839.
16. Bisset L, Beller E, Jull G, Brooks P, Darnell R, Vicenzino B. Mobilisation with movement and exercise, corticosteroid injection, or wait and see for tennis elbow: randomised trial. BMJ (Clinical research ed). 2006;333(7575):939.
17. Hashimoto R, Skelly AC, Brodt E, et al. Autologous Blood or Platelet-Rich Plasma Injections. 2016.
18. Peerbooms JC, Sluimer J, Bruijn DJ, Gosens T. Positive effect of an autologous platelet concentrate in lateral 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;38(2):255-262.
19. Gosens T, Peerbooms JC, van Laar W, den Oudsten BL. Ongoing positive effect of platelet-rich plasma versus corticosteroid injection in lateral epicondylitis: a double-blind randomized controlled trial with 2-year follow-up. Am J Sports Med. 2011;39(6):1200-1208.
20. Krogh TP, Fredberg U, Stengaard-Pedersen K, Christensen R, Jensen P, Ellingsen T. Treatment of lateral epicondylitis with platelet-rich plasma, glucocorticoid, or saline: a randomized, double-blind, placebo-controlled trial. Am J Sports Med. 2013;41(3):625-635.
21. Gautam VK, Verma S, Batra S, Bhatnagar N, Arora S. Platelet-rich plasma versus corticosteroid injection for recalcitrant lateral epicondylitis: clinical and ultrasonographic evaluation. Journal of orthopaedic surgery (Hong Kong). 2015;23(1):1-5.
22. Lebiedzinski R, Synder M, Buchcic P, Polguj M, Grzegorzewski A, Sibinski M. A randomized study of autologous conditioned plasma and steroid injections in the treatment of lateral epicondylitis. International orthopaedics. 2015;39(11):2199-2203.
23. Hastie G, Soufi M, Wilson J, Roy B. Platelet rich plasma injections for lateral epicondylitis of the elbow reduce the need for surgical intervention. J Orthop. 2018;15(1):239-241.
24. Mi B, Liu G, Zhou W, et al. Platelet rich plasma versus steroid on lateral epicondylitis: meta-analysis of randomized clinical trials. The Physician and sportsmedicine. 2017;45(2):97-104.
25. Montalvan B, Le Goux P, Klouche S, Borgel D, Hardy P, Breban M. Inefficacy of ultrasound-guided local injections of autologous conditioned plasma for recent epicondylitis: results of a double-blind placebo-controlled randomized clinical trial with one-year follow-up. Rheumatology (Oxford, England). 2016;55(2):279-285.
26. Schöffl V, Willauschus W, Sauer F, et al. Autologous Conditioned Plasma Versus Placebo Injection Therapy in Lateral Epicondylitis of the Elbow: A Double Blind, Randomized Study. Sportverletzung Sportschaden : Organ der Gesellschaft fur Orthopadisch-Traumatologische Sportmedizin. 2017;31(1):31-36.
27. Linnanmaki L, Kanto K, Karjalainen T, Leppanen OV, Lehtinen J. Platelet-rich Plasma or Autologous Blood Do Not Reduce Pain or Improve Function in Patients with Lateral Epicondylitis: A Randomized Controlled Trial. Clin Orthop Relat Res. 2020.
28. Bohlen HL, Schwartz ZE, Wu VJ, et al. Platelet-Rich Plasma Is an Equal Alternative to Surgery in the Treatment of Type 1 Medial Epicondylitis. Orthop J Sports Med. 2020;8(3):2325967120908952.
29. Lin CP, Chang KV, Huang YK, Wu WT, Ozcakar L. Regenerative Injections Including 5% Dextrose and Platelet-Rich Plasma for the Treatment of Carpal Tunnel Syndrome: A Systematic Review and Network Meta-Analysis. Pharmaceuticals (Basel). 2020;13(3).
30. Kampa RJ, Connell DA. Treatment of tendinopathy: is there a role for autologous whole blood and platelet rich plasma injection? International journal of clinical practice. 2010;64(13):1813-1823.
31. Geary MB, Elfar JC. Rotator Cuff Tears in the Elderly Patients. Geriatr Orthop Surg Rehabil. 2015;6(3):220-224.
32. Chen X, Jones IA, Togashi R, Park C, Vangsness CT, Jr. Use of Platelet-Rich Plasma for the Improvement of Pain and Function in Rotator Cuff Tears: A Systematic Review and Meta-analysis With Bias Assessment. Am J Sports Med. 2019:363546519881423.
33. Kesikburun S, Tan AK, Yilmaz B, Yasar E, Yazicioglu K. Platelet-rich plasma injections in the treatment of chronic rotator cuff tendinopathy: a randomized controlled trial with 1-year follow-up. Am J Sports Med. 2013;41(11):2609-2616.
34. Rha DW, Park GY, Kim YK, Kim MT, Lee SC. Comparison of the therapeutic effects of ultrasound-guided platelet-rich plasma injection and dry needling in rotator cuff disease: a randomized controlled trial. Clinical rehabilitation. 2013;27(2):113-122.
35. Singh P, Madanipour S, Bhamra JS, Gill I. A systematic review and meta-analysis of platelet-rich plasma versus corticosteroid injections for plantar fasciopathy. International orthopaedics. 2017;41(6):1169-1181.
36. Johnson-Lynn S, Cooney A, Ferguson D, et al. A Feasibility Study Comparing Platelet-Rich Plasma Injection With Saline for the Treatment of Plantar Fasciitis Using a Prospective, Randomized Trial Design. Foot & ankle specialist. 2019;12(2):153-158.
37. Peerbooms JC, Lodder P, den Oudsten BL, Doorgeest K, Schuller HM, Gosens T. Positive Effect of Platelet-Rich Plasma on Pain in Plantar Fasciitis: A Double-Blind Multicenter Randomized Controlled Trial. Am J Sports Med. 2019;47(13):3238-3246.
38. Krogh TP, Ellingsen T, Christensen R, Jensen P, Fredberg U. Ultrasound-Guided Injection Therapy of Achilles Tendinopathy With Platelet-Rich Plasma or Saline: A Randomized, Blinded, Placebo-Controlled Trial. Am J Sports Med. 2016;44(8):1990-1997.
39. de Jonge S, de Vos RJ, Weir A, et al. One-year follow-up of platelet-rich plasma treatment in chronic Achilles tendinopathy: a double-blind randomized placebo-controlled trial. Am J Sports Med. 2011;39(8):1623-1629.
40. Scott A, LaPrade RF, Harmon KG, et al. Platelet-Rich Plasma for Patellar Tendinopathy: A Randomized Controlled Trial of Leukocyte-Rich PRP or Leukocyte-Poor PRP Versus Saline. Am J Sports Med. 2019;47(7):1654-1661.
41. Andriolo L, Altamura SA, Reale D, Candrian C, Zaffagnini S, Filardo G. Nonsurgical Treatments of Patellar Tendinopathy: Multiple Injections of Platelet-Rich Plasma Are a Suitable Option: A Systematic Review and Meta-analysis. Am J Sports Med. 2019;47(4):1001-1018.
42. Everhart JS, Cole D, Sojka JH, et al. Treatment Options for Patellar Tendinopathy: A Systematic Review. Arthroscopy. 2017;33(4):861-872.
43. Rodeo SA, Delos D, Williams RJ, Adler RS, Pearle A, Warren RF. The effect of platelet-rich fibrin matrix on rotator cuff tendon healing: a prospective, randomized clinical study. Am J Sports Med. 2012;40(6):1234-1241.
44. Wang A, McCann P, Colliver J, et al. Do postoperative platelet-rich plasma injections accelerate early tendon healing and functional recovery after arthroscopic supraspinatus repair? A randomized controlled trial. Am J Sports Med. 2015;43(6):1430-1437.
45. Flury M, Rickenbacher D, Schwyzer HK, et al. Does Pure Platelet-Rich Plasma Affect Postoperative Clinical Outcomes After Arthroscopic Rotator Cuff Repair? A Randomized Controlled Trial. Am J Sports Med. 2016;44(8):2136-2146.
46. De Carli A, Lanzetti RM, Ciompi A, et al. Can platelet-rich plasma have a role in Achilles tendon surgical repair? Knee surgery, sports traumatology, arthroscopy: official journal of the ESSKA. 2016;24(7):2231-2237.
47. Warth RJ, Dornan GJ, James EW, Horan MP, Millett PJ. Clinical and structural outcomes after arthroscopic repair of full-thickness rotator cuff tears with and without platelet-rich product supplementation: a meta-analysis and meta-regression. Arthroscopy. 2015;31(2):306-320.
48. Saltzman BM, Jain A, Campbell KA, et al. Does the Use of Platelet-Rich Plasma at the Time of Surgery Improve Clinical Outcomes in Arthroscopic Rotator Cuff Repair When Compared With Control Cohorts? A Systematic Review of Meta-analyses. Arthroscopy. 2016;32(5):906-918.
49. Annaniemi JA, Pere J, Giordano S. Platelet-rich plasma versus hyaluronic acid injections for knee osteoarthritis: a propensity-score analysis. Scand J Surg. 2019;108(4):329-337.
50. Laudy AB, Bakker EW, Rekers M, Moen MH. Efficacy of platelet-rich plasma injections in osteoarthritis of the knee: a systematic review and meta-analysis. British journal of sports medicine. 2015;49(10):657-672.
51. Belk JW, Kraeutler MJ, Houck DA, Goodrich JA, Dragoo JL, McCarty EC. Platelet-Rich Plasma Versus Hyaluronic Acid for Knee Osteoarthritis: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Am J Sports Med. 2020:363546520909397.
52. Lin K-Y, Yang C-C, Hsu C-J, Yeh M-L, Renn J-H. Intra-articular Injection of Platelet-Rich Plasma Is Superior to Hyaluronic Acid or Saline Solution in the Treatment of Mild to Moderate Knee Osteoarthritis: A Randomized, Double-Blind, Triple-Parallel, Placebo-Controlled Clinical Trial. Arthroscopy. 2019;35(1):106-117.
53. Navani A, Manchikanti L, Albers SL, et al. Responsible, Safe, and Effective Use of Biologics in the Management of Low Back Pain: American Society of Interventional Pain Physicians (ASIPP) Guidelines. Pain Physician. 2019;22(1s):S1-s74.
54. Akeda K, Yamada J, Linn ET, Sudo A, Masuda K. Platelet-rich plasma in the management of chronic low back pain: a critical review. J Pain Res. 2019;12:753-767.
55. Urits I, Viswanath O, Galasso AC, et al. Platelet-Rich Plasma for the Treatment of Low Back Pain: a Comprehensive Review. Current pain and headache reports. 2019;23(7):52.
56. Tuakli-Wosornu YA, Terry A, Boachie-Adjei K, et al. Lumbar Intradiskal Platelet-Rich Plasma (PRP) Injections: A Prospective, Double-Blind, Randomized Controlled Study. PM & R: the journal of injury, function, and rehabilitation. 2016;8(1):1-10; quiz 10.
57. Bise S, Dallaudiere B, Pesquer L, et al. Comparison of interlaminar CT-guided epidural platelet-rich plasma versus steroid injection in patients with lumbar radicular pain. European radiology. 2020.
58. Chu CR, Rodeo S, Bhutani N, et al. Optimizing Clinical Use of Biologics in Orthopaedic Surgery: Consensus Recommendations From the 2018 AAOS/NIH U-13 Conference. J Am Acad Orthop Surg. 2019;27(2):e50-e63.

• PRP