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MP 2.01.16 Recombinant and Autologous Platelet-Derived Growth Factors as a Treatment of Wound Healing and Other Conditions

 

Medical Policy    
Section
Medicine 
Subsection Last Review Status/Date
Reviewed with literature search/5:2014
Issue
5:2014
Original Policy Date
3/31/96
Return to Medical Policy Index

Disclaimer

Our medical policies are designed for informational purposes only and are not an authorization, or an explanation of benefits, or a contract.  Receipt of benefits is subject to satisfaction of all terms and conditions of the coverage.  Medical technology is constantly changing, and we reserve the right to review and update our policies periodically.


Description

This policy addresses the use of blood-derived growth factors, including recombinant platelet-derived growth factors and platelet-rich plasma (PRP), as a treatment of wounds or other musculoskeletal conditions, including but not limited to adjunctive use in surgical procedures and treatment of diabetic ulcers, ulcers related to venous stasis, lateral epicondylitis (ie, tennis elbow), plantar fasciitis, or Dupuytren contracture.

Background

A variety of growth factors have been found to play a role in wound healing, including platelet-derived growth factors (PDGF), epidermal growth factor, fibroblast growth factors, transforming growth factors, and insulin-like growth factors. Autologous platelets are a rich source of PDGF, transforming growth factors (that function as a mitogen for fibroblasts, smooth muscle cells, osteoblasts), and vascular endothelial growth factors. Recombinant PDGF has also been extensively investigated for clinical use in wound healing.

Autologous platelet concentrate suspended in plasma, also known as (PRP, can be prepared from samples of centrifuged autologous blood. Exposure to a solution of thrombin and calcium chloride degranulates platelets, releasing the various growth factors and results in the polymerization of fibrin from fibrinogen, creating a platelet gel. The platelet gel can then be applied to wounds or may be used as an adjunct to surgery to promote hemostasis and accelerate healing. In the operating room setting, PRP has been investigated as an adjunct to a variety of periodontal, reconstructive, and orthopedic procedures. For example, bone morphogenetic proteins are a type of transforming growth factors, and thus PRP has been used in conjunction with bone-replacement grafting (using either autologous grafts or bovine-derived xenograft) in periodontal and maxillofacial surgeries. Alternatively, PRP may be injected directly into the tissue. PRP has also been proposed as a primary treatment of miscellaneous conditions, such as epicondylitis, plantar fasciitis, and Dupuytren contracture. Injection of PRP for tendon and ligament pain is theoretically related to prolotherapy (discussed in Policy No. 2.01.26). However, prolotherapy involves injection of chemical irritants that are intended to stimulate inflammatory responses and induce release of endogenous growth factors.

PRP is distinguished from fibrin glues or sealants, which have been used for many years as a surgical adjunct to promote local hemostasis at incision sites. Fibrin glue is created from platelet-poor plasma and consists primarily of fibrinogen. Commercial fibrin glues are created from pooled homologous human donors; Tisseel® (Baxter) and Hemaseel® are examples of commercially available fibrin sealants. Autologous fibrin sealants can be created from platelet-poor plasma. This policy does not address the use of fibrin sealants.

Regulatory Status

A recombinant PDGF product, becaplermin gel (Regranex®, McNeil Pharmaceutical) has been approved by the U.S. Food and Drug Administration (FDA). The labeled indication is as follows: "Regranex Gel is indicated for the treatment of lower extremity diabetic neuropathic ulcers that extend into the subcutaneous tissue or beyond and have an adequate blood supply. When used as an adjunct to, and not a substitute for, good ulcer care practices including initial sharp débridement, pressure relief and infection control, Regranex Gel increases the complete healing of diabetic ulcers. The efficacy of Regranex Gel for the treatment of diabetic neuropathic ulcers that do not extend through the dermis into subcutaneous tissue or ischemic diabetic ulcers has not been evaluated." In 2008, the manufacturer added this black box warning to the labeling for 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.”

Augment Bone Graft (Wright Medical) is composed of recombinant PDGF with a conductive scaffold of beta tricalcium phosphate. In August 2013, FDA rejected Wright Medical’s premarket application for use in ankle/foot arthrodesis, expressing concern that “the population enrolled was predominantly low risk and, therefore, may not have warranted the use of either autograft or Augment Bone Graft.” In October 2013, FDA agreed to hold a dispute resolution panel with Wright Medical. Augment Bone Graft is currently available outside of the U.S.

A number of commercially available centrifugation devices are used for the preparation of platelet-rich plasma. For example, AutoloGel™ (Cytomedix) and SafeBlood® (SafeBlood Technologies) are 2 related but distinct autologous blood-derived preparations that can be prepared at the bedside for immediate application. Both AutoloGel and SafeBlood have been specifically marketed for wound healing. Other devices may be used in the operating room setting, such as Medtronic Electromedic, Elmd-500 Autotransfusion system, the Plasma Saver device, or the Smart PreP device. The Magellan Autologous Platelet Separator System (Medtronic) includes a disposables kit designed for use with the Magellan Autologous Platelet Separator portable tabletop centrifuge. BioMet Biologics received marketing clearance through FDA’s 510(k) process for a gravitational platelet separation system (GPS®II), which uses a disposable separation tube for centrifugation and a dual cannula tip to mix the platelets and thrombin at the surgical site. Filtration or plasmapheresis may also be used to produce platelet-rich concentrates. The use of different devices and procedures can lead to variable concentrations of active platelets and associated proteins, increasing variability between studies of clinical efficacy.


Policy

Recombinant platelet-derived growth factor (ie, becaplermin) may be considered medically necessary when used as an adjunct to standard wound management for the following indications (for further information on patient selection criteria, see Policy Guidelines next.)

  • Neuropathic diabetic ulcers extending into the subcutaneous tissue
  • Pressure ulcers extending into the subcutaneous tissue

Other applications of becaplermin are considered investigational, including, but not limited to, ischemic ulcers, ulcers related to venous stasis, and ulcers not extending through the dermis into the subcutaneous tissue.

Use of autologous blood-derived preparations (ie, platelet-rich plasma) is considered investigational.

This includes, but is not limited to, use in the following situations:

  • Treatment of acute or chronic wounds including nonhealing ulcers
  • Adjunctive use in surgical procedures
  • Primary use (injection) for other conditions such as epicondylitis (ie, tennis elbow), plantar fasciitis, or Dupuytren contracture

 


Policy Guidelines

Becaplermin

Appropriate candidates for becaplermin gel for treatment of neuropathic ulcers should meet ALL of the following criteria:

1. Adequate tissue oxygenation, as measured by a transcutaneous partial pressure of oxygen of 30 mm Hg or greater on the foot dorsum or at the margin of the ulcer

2. Full-thickness ulcer (ie, stage III or IV), extending through dermis into subcutaneous tissues

3. Participation in a wound-management program, which includes sharp débridement, pressure relief (ie, non-weight bearing), and infection control

Appropriate candidates for becaplermin gel for the treatment of pressure ulcers should meet ALL of the following criteria:

1. Full-thickness ulcer (ie, Stage III or IV), extending through dermis into subcutaneous tissues

2. Ulcer in an anatomic location that can be off-loaded for the duration of treatment

3. Albumin concentration >2.5 dL

4. Total lymphocyte count >1000

5. Normal values of vitamins A and C

Patients are typically treated once daily for up to 20 weeks or until complete healing. Application of the gel may be performed by the patient in the home.

Becaplermin is available in 2-, 7.5-, and 15-g tubes and is applied in a thin continuous layer, about 1/16 of an inch thick, ie, the thickness of a dime. The amount of the gel used will depend on the size of the ulcer, measured in square centimeters. However, an average-sized ulcer, measuring 3 cm2, treated for an average length of time of 85 days, will require a little more than one 15-g tube. If the ulcer is treated for the maximum length of time of 140 days, 1.75 of the 15-g tubes would be required.

Autologous Blood-Derived Preparations (ie, Platelet-Rich Plasma)

In July 2010, a new CPT category III code for injections of platelet-rich plasma became effective:

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

The instructions issued with the code state that it is not to be reported with codes 20550, 20551, 20600-20610, 20926, 76942, 77002, 77012, 77021 and 86965. Code 0232T includes the harvesting and preparation of the platelet-rich plasma.

For situations other than injection (when 0232T would be reported), no specific CPT codes describe the preparation of autologous blood-derived products but CPT code 86999 (unlisted transfusion medicine procedure) can be used. It has been reported that providers have used CPT code 20926 (tissue graft, other) to describe the overall procedure. It is questionable whether platelet-rich plasma is appropriately considered a tissue graft.

The American Medical Association’s Department of Coding instructs that placement of platelet-rich plasma into an operative site is an inclusive component of the operative procedure performed and not separately reported.

Effective in July 2013, there is a new HCPCS code for this treatment –

G0460 - Autologous platelet rich plasma for chronic wounds/ulcers, including phlebotomy, centrifugation, and all other preparatory procedures, administration and dressings, per treatment.

The code is retroactive to August 2, 2012 for Medicare.


Benefit Application
BlueCard/National Account Issues

Utilization for becaplermin gel is potentially high, particularly if used for off-label indications, or if used outside the setting of adequate and diligent standard wound management. Plans may want to consider active implementation and management of this policy to ensure that becaplermin is used as part of a program of wound management, as described in the Policy Guidelines. 


Rationale

This policy was created in 1996 and updated periodically using the MEDLINE database. The most recent review was performed through March 25, 2014. Following is a summary of key references to date, focusing on systematic reviews and randomized controlled trials (RCTs).

Recombinant Platelet-Derived Growth Factor (Becaplermin Gel)

Diabetic Neuropathic Ulcers: This policy regarding the use of becaplermin gel was originally based on a 1999 TEC Assessment,(1) which concluded that the evidence supports the conclusion that becaplermin treatment, in conjunction with good wound care, improves the health outcomes of patients with chronic neuropathic diabetic ulcers that meet the patient selection criteria defined here. Becaplermin gel plus good wound care resulted in a 43% complete wound-closure rate, compared with 28% for patients treated with good wound care alone. Becaplermin gel also appeared to reduce the average time to complete wound closure.

An industry-sponsored study assessed the effectiveness of recombinant platelet-derived growth factors (PDGF) on diabetic neuropathic foot ulcers in actual clinical practice.(2) Subjects (from a cohort of 24,898 patients in wound-care centers) whose wounds did not heal over an 8-week observation period were eligible for the study and were assessed over a period of 20 weeks or until they healed. Any subject with an open wound who was lost to follow-up was considered unhealed. Of the nearly 25,000 patients treated for foot ulcers, 2394 (9.6%) received recombinant PDGF. A propensity score method with covariates to statistically model treatment selection was used to adjust for selection bias; results were stratified by 5 propensity score groups. Overall, the rate of healing was 26.5% in the control group and 33.5% in patients treated with recombinant PDGF. The relative risk, controlling for the propensity to receive PDGF, was 1.32 for healing and 0.65 for amputation (6.4% vs 4.9%, respectively). Analysis also indicated that those who received PDGF were more likely to be younger, male, and have older wounds, factors not known to affect wound healing. These results support clinical effectiveness of recombinant PDGF for treatment of diabetic neuropathic foot ulcers in actual clinical practice.

Pressure Ulcers: Results of a randomized study focusing on the use of becaplermin gel as a treatment of pressure ulcers was published in 1999.(3) The patient selection criteria for this study are summarized in the Policy Guidelines section, but most importantly included full-thickness ulcers and an anatomic location where pressure could be off-loaded during treatment. This latter patient selection criterion may limit the number of patients with pressure ulcers who would be considered candidates for becaplermin therapy. Patients were randomized to 1 of 4 parallel treatment groups and received either a placebo or 1 of 3 doses of becaplermin. All patients received a standardized program of good wound care. In the 2 groups of patients treated with once daily doses of becaplermin (either 100 or 300 µg/g), the incidence of complete healing was significantly improved compared with the placebo group. There was no difference in outcome between the 100 and 300 µg/g group, suggesting that there is no clinical benefit in increasing the dose above 100 µg/g. A third group of patients received becaplermin 100 µg/g twice a day. This group did not report an improved outcome compared with placebo, a finding that is unexplained.

Hypertensive Leg Ulcers: In 2011, Senet et al published results of a multicenter randomized double-blind controlled trial of becaplermin gel as a treatment of hypertensive ulcers.(4) There was no significant difference between the becaplermin (n=28) and control hydrogel (n=31) groups for any of the outcome measures, which included complete closure rates after 8 and 12 weeks, changed ulcer area, and changed ulcer-related pain and quality of life.

Acute Traumatic Wounds: Topical recombinant PDGF has also been investigated for repair of work-related fingertip injuries. One study used alternate assignment to “randomize” 50 patients (fingertip wound area of 1.5 cm or more, with or without phalangeal exposure) to daily treatment with PDGF or surgical reconstruction.(5) Statistical analysis showed that the baseline characteristics of the 2 groups were similar for patient age, wound area (2.2–2.4 cm), and distribution of fingertip injuries across the digits. Assessment by an independent physician showed that in comparison with the surgical intervention, treatment with recombinant PDGF resulted in faster return to work (10 vs 38 days, respectively) and wound healing (25 vs 35 days, respectively) and a reduction in functional impairment (10% vs 22%, respectively) and need for physiotherapy (20% vs 56%, respectively). Fingertips treated with PDGF were also reported to have satisfactory esthetic results, while surgically treated fingertips were shorter and often unsightly. These results, if confirmed, could lead to improvement in health outcomes for patients with fingertip injury. However, the present study is limited by the small sample size, the method of randomization, and the potential for investigator bias (although the investigators did blind the examining physician from treatment allocation, the actual treatment may have been obvious). Additional RCTs are needed.

Ankle/Hindfoot Arthrodesis: The North American Orthopedic Foot and Ankle Study Group reported an industry-sponsored, FDA-regulated, multicenter noninferiority trial of PDGF plus an osteoconductive matrix (Augment Bone Graft) compared with autograft in 397 patients undergoing ankle or hindfoot fusion.(6) Two hundred sixty patients (395 joints) underwent arthrodesis with Augment Bone Graft, and 137 patients (203 joints) underwent arthrodesis with autograft. Only the radiologist was blinded to treatment. Noninferiority (single-sided 10-point margin) was observed for the end point of fusion, which was observed by CT in 61.2% of PDGF patients and 62% of autograft patients. Clinically, 86.2% of PDGF patients and 87.6% of autograft patients were considered healed at 52 weeks. Fourteen of 16 secondary end points met noninferiority at 24 weeks and 15 of 16 secondary end points met noninferiority at 52 weeks. These included clinical success rate, SF-12 Physical Component Score, Foot Function Index, American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale (AHFS) total score, fusion site pain and weight-bearing pain. Augment Bone Graft is not approved for marketing in the U.S.

Adverse Effects: Growth factors cause cells to divide more rapidly. It is for this reason that the manufacturer continued to monitor studies begun before Regranex was approved in December 1997 for any evidence of adverse effects, such as increased numbers of cancers. In a long-term safety study completed in 2001, more deaths from cancer occurred in people who used Regranex than in those who did not use it. Following the report of the study completed in 2001, an additional study was performed using a health insurance database that covered the period from January 1998 through June 2003. This study used the database to identify 2 groups of patients with similar diagnoses, drug use, and use of health services, 1 of which used Regranex and 1 group that did not. The results of this study showed that deaths from cancer were higher for patients who were given 3 or more prescriptions for treatment with Regranex than those who were not treated with Regranex. No single type of cancer was identified, but deaths from all types of cancer combined were observed. In 2008, FDA concluded that the increase in the risk of death from cancer in patients who used 3 or more tubes of Regranex was 5 times higher than in those patients who did not use Regranex. The risk of getting new cancers among Regranex users was not increased compared with nonusers, although the duration of follow-up of patients in this study was not long enough to detect new cancers.

Section Summary

Results from RCTs show improved rates of healing with use of recombinant PDGF for diabetic neuropathic ulcers and pressure ulcers. The increase in rate of healing must be balanced with the potential for increased risk from cancer. Evidence is insufficient to determine whether becaplermin gel improves health outcomes when used to treat other types of wounds, including ischemic or chronic venous ulcers or acute traumatic wounds.

Autologous Blood-Derived Preparations (ie, Platelet-Rich Plasma)

The policy on platelet-derived wound-healing formula was originally derived from a 1992 TEC Assessment,(7) which primarily focused on the Procuren process, referred to as a platelet-derived wound-healing formula. This preparation is no longer commercially available. At the present time, there are a large number of devices available for the preparation of platelet-rich plasma (PRP) or PRP gel. The amount and mixture of growth factors produced by different cell-separating systems are variable, and it is also uncertain whether platelet activation before injection is necessary.(8-12)

A number of systematic reviews of the evidence on PRP have been published. A 2012 systematic review included 23 randomized trials and 10 prospective cohort studies that compared PRP with placebo, corticosteroids, or a standard procedure.(13) For most of the studies, the outcome measures differed, but 6 RCTs (n=358) and 3 prospective cohort studies (n=88) reported results of PRP using a visual analog score (VAS) and were combined for analysis. These studies assessed injuries to the acromion, rotator cuff, lateral humeral epicondyle, anterior cruciate ligament (ACL), patella, tibia, and spine. Follow-up ranged from 6 weeks to 24 months. Of 22 RCTs that evaluated functional outcomes, 6 showed a functional benefit of PRP, 15 showed no difference between PRP and the control, and 1 showed a significant functional advantage for the control group. Interpretation of this systematic review is limited by the combination of a wide variety of conditions, as well as the lack of standardization of platelet-separation techniques and outcome measures in the primary literature.

A 2012 Cochrane review included 9 RCTs (325 participants) on PRP for treating chronic wounds.(14) This review was restricted to studies where PRP was compared with no additional treatment or a placebo. Four RCTs included patients with mixed chronic wounds, 3 included patients with venous leg ulcers, and 2 RCTs included patients with diabetic foot ulcers. Only 1 study was considered to be at low risk of bias. After a median treatment time of 12 weeks, there was no significant difference between the PRP and control groups in complete healing of diabetic foot ulcers, venous leg ulcers, or mixed chronic wounds. There was no significant difference in the area epithelialized in 3 RCTs of mixed chronic wounds. In 2 RCTs of mixed chronic wounds, there was a significant difference favoring PRP in the wound area that was healed. The review concluded that there is no current evidence to suggest that autologous PRP is of value for treating chronic wounds.

Earlier systematic reviews have come to similar conclusions. For example, a 2009 systematic review identified 42 controlled trials on PRP, 20 of these were RCTs and included in the systematic review.(15) The 20 RCTs comprised 11 studies on oral and maxillofacial surgery, 7 on chronic skin ulcers, and 2 on surgery wounds. A 2010 systematic review of autologous growth factor injections in chronic tendinopathy found no high-quality studies using PRP.(16) An industry-funded systematic review from 2011 included 21 studies on PRP gel for cutaneous wound healing, 12 of which were RCTs.(17) There were 3 main types of wounds, including open chronic wounds, acute surgical wounds with primary closure, and acute surgical wound with secondary closure. Study quality was found to vary considerably, with 3 studies rated as high quality and 6 rated as poor quality. Two additional studies could not be rated because they were published only as an abstract and letter. The meta-analysis of the effect of PRP on complete wound healing of chronic wounds is limited by the inclusion of poor-quality studies. There were no high-quality RCTs that showed an improvement in complete healing with PRP.

Key references on PRP for specific indications are described next.

Achilles Tendinopathy: A single center, randomized double-blind, placebo-controlled trial of PRP injection in patients with chronic midportion Achilles tendinopathy was reported by de Vos et al in 2010.(18) Fifty-four patients were randomized to receive PRP or saline injection, and all patients performed eccentric exercises. The Victorian Institute of Sports Assessment-Achilles (VISA-A) questionnaire evaluating pain score and activity level was completed at baseline and at 6, 12, and 24 weeks. The mean VISA-A score improved significantly after 24 weeks in both groups, and the between-group difference was not statistically significant. There were no significant differences on secondary measures of patient satisfaction and number of patients returning to their desired sport. No additional trials of PRP for chronic Achilles tendinopathy were identified in a 2013 Cochrane review.(19)

Acute Traumatic Wounds: Kazakos et al reported a prospective controlled study of the treatment of acute traumatic wounds with platelet gel in 59 consecutive patients (27 PRP, 32 controls).(20) Conventional treatment consisted of topical washing and cleaning of the wounds, removal of the necrotic tissue, and dressing with Vaseline gauze every 2 days. In all patients with open tibial fractures, an external fixation system was applied. PRP gel, prepared with specialized tubes and a bench-top centrifuge, was applied to the wounds after surgical débridement and placement of the external fixation system. The time needed for preparation and application of the PRP gel was 52 minutes. PRP gel was then applied to the wounds once weekly in the outpatient clinic until there was adequate tissue regeneration (mean, 21 days) to undergo reconstructive plastic surgery. Control patients receiving conventional treatment required a mean of 41 days for adequate tissue regeneration. Pain scores were significantly lower in the PRP-treated patients at 2 and 3 weeks (VAS score of 58 PRP vs 80 controls). Although these results are encouraging, additional study with a larger number of subjects is needed.

ACL Reconstruction: A 2013 Cochrane review of platelet-rich therapies for musculoskeletal soft tissue injuries identified 4 trials (203 patients) on PRP used in conjunction with ACL reconstruction.(19) Pooled data found no significant difference in International Knee Documentation Committee (IKDC) scores between the PRP and control groups. The largest trial is by Ninet et al, who randomized 100 patients to undergo arthroscopic ACL reconstruction with or without PRP.(21) The use of PRP on the graft and inside the tibial tunnel in patients treated with bone-patellar tendon-bone allografts had no discernable clinical or biomechanical effect at 2-year follow-up.

Hip Fracture: In 2013, Griffin et al reported a single-blind randomized trial of PRP for the treatment of hip fractures in patients aged 65 years and older.(22) Two hundred patients underwent internal fixation of a hip fracture with cannulated screws and were randomly assigned to receive standard-of-care fixation or standard-of-care fixation with injection of PRP into the fracture site. The primary outcome measure was the failure of fixation within 12 months, defined as any revision surgery. The overall risk of revision by 12 months was 36.88% and the risk of death was 21.5%. There was no significant risk reduction (39.74% control and 34.15% PRP) or significant difference between groups in most of the secondary outcome measures. For example, mortality was 23% in the control group and 20% in the PRP group. The length of stay was significantly reduced in the PRP-treated group (median difference, 8 days). There is a potential for bias from the nonblinded treating physician in this measure.

Lateral Epicondylitis (Tennis Elbow): A 2014 systematic review concluded that there is strong evidence that PRP is not effective for lateral epicondylar tendinopathy.(23) Six studies were included in the review, 4 of which were considered to be of high quality based on the PEDro score. The authors reported that 3 of 4 high-quality studies and 2 low-quality studies (including Mishra et al, described next) showed no significant benefit when compared with a control group (corticosteroids, autologous whole blood, saline, needling), while 1 high-quality study (Peerbooms et al, described next) showed a beneficial effect of a PRP injection when compared with a corticosteroid injection.

The double-blind randomized trial that favored PRP for lateral epicondylitis was reported by Peerbooms et al in 2010, with 2-year follow-up reported by Gosens et al in 2011.(24,25) One hundred patients with chronic (>6 months) epicondylitis were randomized, 49 to receive corticosteroid injection and 51 to receive PRP injection. Success was defined as 25% reduction in pain on VAS or Disabilities of the Arm, Shoulder, and Hand (DASH) outcomes measure score after 1 year without a reintervention. Initially, mean VAS was 70.1 in the PRP-treated patients and 65.8 in the corticosteroid group. DASH scores were 161.3 and 131.2, respectively (p<0.001). At 4 and 8 weeks after injection, outcomes on VAS and DASH scores were significantly better in the corticosteroid group. At 12 weeks, between-group differences were not significant. After 1 year, 73% of PRP and 49% of corticosteroid-treated patients met criteria for success on pain VAS; 73% of the PRP group and 51% the steroid group were successful using DASH outcome measures (p=0.005). At 2 years, both VAS and DASH scores were significantly better in the PRP group (21.3 and 17.6, respectively) compared with the corticosteroid group (42.4 and 36.5). Success on the DASH was achieved by 73% of the PRP group and 39% of the corticosteroid group, while more patients in the corticosteroid group (47% vs 14%) had deteriorated at 2 years.

In 2014, Mishra et al reported a manufacturer-sponsored multicenter double-blind RCT of 230 patients with lateral epicondylitis.(26) Patients were randomized to PRP with needling or to needling alone. The prespecified outcome was the proportion of patients with at least a 25% decrease in pain score on VAS at 12 weeks. There was no significant difference in treatment success rates (25% or 50% VAS) at 12 weeks. A request from FDA led to an extension of the study to 24 weeks in newly enrolled patients (n=136) to further evaluate safety and efficacy. Blinded analysis of this subset at 24 weeks found a modest increase in treatment success rates; using a threshold of 25% or greater reduction in pain, 83.9% of PRP-treated patients and 68.3% of control patients achieved treatment success. Using a threshold of 50% or greater reduction in pain, 82.1% of PRP-treated patients and 60.3% of control patients achieved treatment success. There were no significant differences between the groups on the tennis elbow questionnaire at 8-, 12-, or 24-week follow-up.

Krogh et al reported a double-blind placebo-controlled RCT in 60 patients with chronic lateral epicondylitis in 2013. (27) Patients were randomized to receive either a blinded injection of PRP, saline, or corticosteroid injection. To maintain blinding, a blood sample was taken from all patients, and patients were blindfolded during the blood sampling and injections. At 1 month, corticosteroid injections reduced pain to a greater extent than either PRP or saline. At 3-month follow-up, there was no significant difference between the groups in the primary end point of pain reduction. Corticosteroid injection was more effective than saline or PRP in reducing color Doppler activity and tendon thickness.

Section Summary

Evidence on the efficacy of PRP for lateral epicondylitis was summarized in a 2014 systematic review, and includes 4 high-quality and 2 low-quality RCTs. One high-quality trial showed a benefit of PRP when compared with corticosteroid, while another high-quality trial favored corticosteroid injection. A 2014 study by Mishra et al reported some benefit of PRP plus needling compared with needling alone at 24-week follow-up. However, confidence in the validity of this result is limited by: (1) there was no significant benefit of PRP for the primary end point at 12 weeks, (2) the difference in treatment success between PRP and controls at 24 weeks was modest (15.6%), and (3) no significant differences were found on the tennis elbow questionnaire at either 12 or 24 weeks. Because of these limitations in the data, the efficacy of PRP injections for tennis elbow remains uncertain.

Long-Bone Nonunion: A 2012 Cochrane review found only 1 small (n=21) RCT of PRP for long-bone healing.(28) However, only studies where PRP was compared with no additional treatment or a placebo were included in the review; therefore the authors did not include the larger RCT by Calori et al described next.

Calori et al compared application of PRP or recombinant human bone morphogenetic protein-7 (rhBMP-7) for the treatment of long-bone nonunions in an RCT with 120 patients and 10 surgeons.(29) Inclusion criteria were posttraumatic atrophic nonunion for at least 9 months, with no signs of healing over the last 3 months, and considered as treatable only by means of fixation revision. Autologous bone graft had been used in a prior surgery in 23 cases in the rhBMP-7 group and in 21 cases in the PRP group. Computer-generated randomization was developed to create 2 homogeneous groups; there were generally similar numbers of tibial, femoral, humeral, ulnar, and radial nonunions in the 2 groups. Following randomization, patients underwent surgery for nonunion, including bone grafts according to the surgeon’s choice (66.6% of rhBMP-7, 80% of PRP patients). Clinical and radiologic evaluations by 1 radiologist and 2 surgeons trained in the study protocol revealed fewer unions in the PRP group (68%) compared with the rhBMP-7 group (87%). Clinical and radiographic healing times were also found to be slower by 13% to 14% with PRP.

Osteochondral Lesions: In 2012, Mei-Dan et al reported a quasirandomized trial of 29 patients with 30 osteochondral lesions of the talus assigned to 3 intra-articular injections of hyaluronate or PRP.(30) At 28-week follow-up, scores on the AOFAS-AHFS improved to a greater extent in the PRP group (from 68 to 92) than the hyaluronate group (from 66 to 78). Subjective global function also improved to a greater extent in the PRP group (from 58 to 91) than the hyaluronate group (from 56 to 73). Interpretation of the composite measures of VAS pain and VAS function is limited by differences in the groups at baseline. Neither the patients nor the evaluators were blinded to treatment in this small study.

Osteoarthritis: A 2014 systematic review of PRP for degenerative cartilage pathology included 5 RCTs, 3 quasirandomized controlled trials, and 8 single-arm prospective series (total of 1543 patients) comparing PRP with hyaluronic acid (HA; 4 RCTs and 2 quasi-randomized) or saline (1 RCT).(31) Meta-analysis of functional outcomes found that the effectiveness of PRP was greater than that of HA and improved over the course of 12 months. Fewer than 3 injections, single spinning, and lack of additional activators led to greater uncertainty in the treatment effects. PRP also had lower efficacy in patients with higher degrees of cartilage degeneration. Results were consistent when analyzing only RCTs, but asymmetry in funnel plots indicated that significant publication bias was a concern. Some of the studies included in the systematic review are described in greater detail next.

Several RCTs from Europe and Asia have been reported, with mixed results. A double-blind study from 2012 randomized 109 patients with knee chondropathy or osteoarthritis (Kellgren-Lawrence grades I, II, or III) to 3 weekly injections of PRP (previously frozen aliquot) or HA.(32) At 12 months of follow-up, there was significant improvement on IKDC, VAS, TEGNER, and KOOS scores in both groups, but no significant difference between the groups. Another RCT from 2012 compared 4 intra-articular injections of PRP or HA in 120 patients with gonarthrosis (early stage knee arthritis, Kellgren-Lawrence grades I, II, or III).(33) At 4 weeks, both groups showed improvement in Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores compared with baseline. In this nonblinded study, WOMAC scores for the PRP group continued to improve over 24 weeks (79.6 at baseline, 49.6 at 4 weeks, 36.5 at 24 weeks), whereas WOMAC scores in the HA group declined in the posttreatment period (75.4 at baseline, 49.6 at 4 weeks, 65.1 at 24 weeks). In 2013, Patel et al reported a double-blind placebo-controlled RCT with 78 patients (156 knees). This study compared a single injection of PRP, 2 injections of PRP, or a single injection of saline. Adverse effects at the time of injection were observed in 22% of patients in the 1 injection PRP group and 44% in the 2 injection PRP group, compared with none in the saline group. At 6-month follow-up, WOMAC scores had improved in the 2 PRP groups but not in the control group. VAS pain scores improved from 4.54 to 2.16 after a single injection of PRP and from 4.64 to 2.54 after 2 injections of PRP. VAS scores did not change in the placebo-control group (from 4.57 at baseline to 4.61 at 6-month follow-up).

A 2009 series from Europe described a prospective study of intra-articular injection of PRP in 100 consecutive patients affected by chronic degenerative cartilage lesions.(34) Fifty-eight knees presented with a degenerative chondral lesion, 33 with early osteoarthritis, and 24 had advanced osteoarthritis. Three injections were administered at 21-day intervals. Evaluation was conducted in 91 patients (91% follow-up) before and at the end of the 3 treatments and at 6 and 12 months after treatment. The IKDC objective score improved from 46% (of normal and nearly normal knees) to 78% at the end of therapy, declining to 67% at 12-month follow-up. The IKDC subjective score improved from 41 to 63 after treatment, with a score of 61 at 12-month follow-up. Treatment was less effective in older, heavier, and more advanced osteoarthritis patients than in younger patients with less severe chondral damage.

Patellar Tendon: In 2012, de Almeida et al reported a small (n=27) randomized trial of the effect of PRP gel on the harvest site of the patellar tendon during ACL reconstruction.(35) VAS for pain in the postoperative period was significantly lower in the PRP group compared with the control group (3.8 vs 5.1). At 6 months, assessment by magnetic resonance imaging (MRI) showed a smaller gap in the patellar tendon in the PRP group (4.9 mm vs 9.4 mm), but there was no significant difference between groups for the Tegner questionnaire or isokinetic testing.

Plantar Fasciitis: The 2012 systematic review by Sheth et al identified 3 uncontrolled studies that evaluated the effect of autologous blood injections.(13) In 2014 Monto reported an RCT of PRP versus corticosteroid in 40 patients with chronic severe plantar fasciitis.(36) There was an apparent difference in the age and baseline score of the 2 groups. Blinded assessment with AOFAS hindfoot score at 3, 6, 12, and 24 months showed a temporary improvement with the corticosteroid group with a return to near baseline levels (score, 58) by 12 months. In the PRP group the AOFAS score increased from 37 at baseline to 95 at 3 months and remained elevated through 24 months with a final score of 92. The PRP system used in this study was the Accelerate Sport Platelet Concentration system (Exactech). Confirmation of these results in a larger double-blind RCT with other concentration systems would allow greater certainty regarding the efficacy of PRP in plantar fasciitis.

Rotator Cuff Repair: There are a number of small double-blind RCTs that have evaluated the efficacy of PRP in combination with repair of the rotator cuff. Most these studies show no significant benefit of PRP. For example, Castricini et al randomized 88 patients with a rotator cuff tear to arthroscopic repair without (n=45) or with (n=43) augmentation with platelet-rich fibrin matrix.(37) At average follow-up of 20.2 months (range, 16-30 months), both groups demonstrated statistically significant improvement in the primary end point (Constant scores evaluating pain, activities of daily living, range of movement, power), but the between-group difference was not significant. In 2012, Rodeo et al reported an RCT arthroscopic rotator cuff tendon repair with or without PRP (platelet rich fibrin matrix) in 79 patients.(38) Follow-up at 6 weeks, 3 months, and 12 months postoperatively found no significant differences between the PRP and control groups for tendon healing, tendon vascularity, manual muscle strength, or clinical rating scales. Logistic regression analysis suggested that PRP might have a negative effect on healing.

A double-blind quasirandomized trial from 2013 assigned 60 patients in alternating order to receive rotator cuff surgery with or without PRP (platelet rich fibrin matrix).(39) Mean surgery time was increased by about 10 minutes in the PRP group. At 1-year follow-up, there was no significant difference between the groups in VAS pain scores, narcotic use, recovery of motion, simple shoulder test (SST), and American Shoulder and Elbow Surgeons (ASES) shoulder scores. Mean University of California-Los Angeles (UCLA) scores were slightly lower in the PRP group (27.94 vs 29.59). There were no significant differences between the groups on MRI scans at 3 to 5 month follow-up.

In 2012, Gumina et al reported an RCT of platelet-leukocyte membrane in 80 patients with full-thickness rotator cuff tear randomized to arthroscopic repair with or without PRP.(40) Both age and Constant score were significantly different at baseline. At a mean 13-month follow-up, the SST and the change in Constant score did not differ significantly between the 2 groups. Independent evaluation with MRI found that rotator cuff retears occurred only in the control group and that the use of the PRP membrane resulted in significantly better repair integrity.

Randelli et al randomized 53 patients in a double-blind study to arthroscopic rotator cuff repair with or without PRP.(41) VAS pain scores in the PRP group were lower than controls at baseline (4.8 vs 6.4) through 30 days after surgery (1.1 vs 2.4). At 3 months after surgery, the PRP group had higher scores on Constant scores (65.0 vs 57.8) and the SST (8.9 vs 7.1), UCLA (26.9 vs 24.2) and strength in external rotation (3.0 vs 2.1). There was no difference in functional outcomes between the groups at 6, 12, and 24 months after surgery and no difference in the healing rate measured by MRI at 1 year or more after surgery. This study is limited by the difference in VAS between the groups at baseline.

A small double-blind RCT of PRP for rotator cuff healing without surgical repair was reported by Rha et al in 2012.(42) In this study, 39 patients with tendinosis or a partial tear were randomized to 2 sessions of dry needling or 2 PRP injections. For dry needling, a needle was passed through the lesion of the tendon approximately 40 to 50 times. PRP was injected into or around the lesion under ultrasound guidance. Both groups showed an improvement in the Shoulder Pain and Disability Index (SPDI) over the 6 months of the study. At 2 weeks, 3 months, and 6 months after the treatment, the mean SPDI score was significantly better in the PRP group (17.7 vs 29.5). Range of motion was generally not different between the groups.

A 2013 Cochrane review that pooled data for long-term function from 6 trials (4 previously described) of PRP applied with rotator cuff repair showed no statistically or clinically significant differences between the PRP and control groups.(19) Trials discussed both here and in the Cochrane review are by Castricini et al (2011), Gumina et al (2012), Randelli et al (2011), and Rodeo et al (2012).

Section Summary

The literature on PRP for rotator cuff repair consists of a number of small double-blind RCTs that have evaluated the efficacy of PRP membrane or matrix combined with surgical repair of the rotator cuff. Results are mixed, with most studies showing little or no benefit of PRP. Pooling of data from these trials showed no statistically or clinically significant benefit of PRP.

Spinal Fusion: No randomized trials on PRP in spinal fusion were identified; however, 2 controlled studies found no difference in fusion rates with use of a platelet gel or platelet glue.(43,44)

Subacromial Decompression Surgery: Everts et al reported a rigorously conducted, small (n=40) double-blinded RCT of platelet and leukocyte-rich plasma (PLRP) gel following open subacromial decompression surgery in a carefully selected patient population.(45) Blood was drawn from all patients after induction of anesthesia to maintain blinding. PLRP with autologous thrombin was injected into both the subacromial intracapsular space and the subcutaneous layer covering the incision during wound closure. Postoperative examinations at 1, 2, 4, and 6 weeks were performed by independent evaluators; unique patient identifier codes were used to maintain patient and investigator blinding. Neither self-assessed nor physician-assessed instability were improved. Both subjective pain and use of pain medication were lower in the PLRP group across the 6 weeks of measurements. For example, at 2 weeks after surgery, VAS scores for pain were lower by about 50% in the PLRP group (close to 4 in the control group and close to 2 in the PLRP group), and only 1 patient (5%) was taking pain medication compared with 10 (50%) control patients. Objective measures of range of motion showed clinically significant improvement in the PLRP group across the 6-week assessment period, while patients reported improvements in activities of daily living such as ability to sleep on the operated shoulder at 4 weeks after surgery and earlier return to work.

Tonsillectomy: A double-blind RCT assessed the efficacy of PRP following tonsillectomy in 70 children, aged 4 to 15 years.(46) The PRP was prepared during the surgery and placed into the tonsil beds of half of the children, where it was directly visible. To compare pain symptoms and recovery, a daily diary was completed by either the patient or family member for 10 days after surgery. A FACES pain scale was used for the children aged 4 to 7 years, while a numbered pain scale was used for children older than 7 years. Diaries from 83% of the patients showed no differences in pain, medication doses, activity, and days eating solid foods between the 2 conditions.

Wound Closure: A study of PRP applied to saphenous vein harvest sites after wound closure found no difference in the incidence of wound infection or cosmetic result.(47)

Summary

Results from randomized controlled trials (RCTs) show improved rates of healing with use of recombinant platelet-derived growth factor (PDGF) for diabetic neuropathic ulcers and pressure ulcers. Evidence is insufficient to determine whether becaplermin gel improves health outcomes when used to treat other types of wounds, including ischemic or chronic venous ulcers or acute traumatic wounds. Recombinant PDGF in combination with an osteoconductive agent is not currently approved for marketing in the U.S.

For platelet-rich plasma (PRP) treatment, there are numerous small controlled trials for a wide variety of conditions. The potential benefit of PRP has received considerable interest due to the appeal of a simple, safe, low-cost, and minimally invasive method of applying growth factors. The oldest and most established evidence is in the area of dental surgery, which is outside the scope of medical policy. Recent literature indicates an increasing number of RCTs for other conditions, and a search of the clinical trials database (available online at: www.clinicaltrials.gov) reveals that many more RCTS are in progress.

Current results of PRP trials are mixed. A recent systematic review found that a greater proportion of studies reported no benefit from PRP than studies that reported a benefit. It is unknown if the mixed results are due to variability in the conditions studied and outcomes measured, to differences in platelet separation technique, concentration or activation, or to differences in the timing and frequency of administration. Additional studies are needed to resolve these issues. Therefore, PRP as a primary treatment for acute or chronic wounds, or as an adjunct to surgical procedures, is considered investigational.

Practice Guidelines and Position Statements

American Academy of Orthopaedic Surgeons (AAOS) 2013 guidelines were unable to recommend for or against growth factor injections and/or PRP for patients with symptomatic osteoarthritis of the knee.(48) A recommendation of inconclusive is based on a single low-quality study and conflicting findings that do not allow a recommendation for or against the intervention. The AAOS recommendation is based on 3 studies that were published before May 2012.

In 2009, the United Kingdom’s National Institute for Health and Clinical Excellence (NICE) issued guidance on use of autologous blood injection for tendinopathy.(49) NICE concluded that the current evidence on the safety and efficacy of autologous blood injection for tendinopathy is inadequate in quantity and quality. NICE recommends this procedure should only be used with special arrangements for clinical governance, consent, and audit or research.

In 2013, NICE issued guidance on use of autologous blood injection (with or without techniques for producing PRP) for plantar fasciitis.(50) NICE concluded that the evidence on autologous blood injection for plantar fasciitis raises no major safety concerns but that the evidence on efficacy is inadequate in quantity and quality. Therefore, this procedure should only be used with special arrangements for clinical governance, consent and audit or research. In addition, physicians should ensure that patients understand the uncertainty about the procedure's efficacy, be aware of alternative treatments, and be provided with clear written information.

Medicare National Coverage

In 2012, Medicare revised its national coverage decision on autologous blood-derived products for chronic nonhealing wounds.(51) This replaces noncoverage decisions from 2004 and 2008.(52,53) CMS covers autologous PRP only for patients who have chronic nonhealing diabetic, pressure, and/or venous wounds and when all the following conditions are met:

  • The patient is enrolled in a clinical research study that addresses the following questions using validated and reliable methods of evaluation. Clinical study applications for coverage pursuant to this National Coverage Determination (NCD) must be received by August 2, 2014.
  • The clinical research study must meet the requirements specified below to assess the effect of PRP for the treatment of chronic non-healing diabetic, pressure, and/or venous wounds. The clinical study must prospectively address whether Medicare beneficiaries who have chronic non-healing diabetic, pressure, and/or venous wounds who receive well-defined optimal usual care, along with PRP therapy, experience clinically significant health outcomes compared to patients who receive well-defined optimal usual care for chronic non-healing diabetic, pressure, and/or venous wounds as indicated by addressing at least one of the following:
    1. complete wound healing;
    2. ability to return to previous function and resumption of normal activities; or
    3. reduction of wound size or healing trajectory, which results in the patient’s ability to return to previous function and resumption of normal activities

References:

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  2. Margolis DJ, Bartus C, Hoffstad O et al. Effectiveness of recombinant human platelet-derived growth factor for the treatment of diabetic neuropathic foot ulcers. Wound Repair Regen 2005; 13(6):531-6.
  3. Rees RS, Robson MC, Smiell JM et al. Becaplermin gel in the treatment of pressure ulcers: a phase II randomized, double-blind, placebo-controlled study. Wound Repair Regen 1999; 7(3):141-7.
  4. Senet P, Vicaut E, Beneton N et al. Topical treatment of hypertensive leg ulcers with platelet-derived growth factor-BB: a randomized controlled trial. Arch Dermatol 2011; 147(8):926-30.
  5. Freedman BM, Oplinger EH, Freedman IS. Topical becaplermin improves outcomes in work related fingertip injuries. J Trauma 2005; 59(4):965-8.
  6. DiGiovanni CW, Lin SS, Baumhauer JF et al. Recombinant human platelet-derived growth factor-BB and beta-tricalcium phosphate (rhPDGF-BB/beta-TCP): an alternative to autogenous bone graft. J Bone Joint Surg Am 2013; 95(13):1184-92.
  7. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Growth factors for wound healing. TEC Evaluations 1992; Volume 7, Pages 352-77.
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  9. Eppley BL, Woodell JE, Higgins J. Platelet quantification and growth factor analysis from platelet-rich plasma: implications for wound healing. Plast Reconstr Surg 2004; 114(6):1502-8.
  10. Kevy SV, Jacobson MS. Comparison of methods for point of care preparation of autologous platelet gel. J Extra Corpor Technol 2004; 36(1):28-35.
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  12. Mazzucco L, Balbo V, Cattana E et al. Not every PRP-gel is born equal. Evaluation of growth factor availability for tissues through four PRP-gel preparations: Fibrinet, RegenPRP-Kit, Plateltex and one manual procedure. Vox Sang 2009; 97(2):110-8.
  13. Sheth U, Simunovic N, Klein G et al. Efficacy of autologous platelet-rich plasma use for orthopaedic indications: a meta-analysis. J Bone Joint Surg Am 2012; 94(4):298-307.
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  15. Martinez-Zapata MJ, Marti-Carvajal A, Sola I et al. Efficacy and safety of the use of autologous plasma rich in platelets for tissue regeneration: a systematic review. Transfusion 2009; 49(1):44-56.
  16. de Vos RJ, van Veldhoven PL, Moen MH et al. Autologous growth factor injections in chronic tendinopathy: a systematic review. Br Med Bull 2010; 95:63-77.
  17. Carter MJ, Fylling CP, Parnell LK. Use of platelet rich plasma gel on wound healing: a systematic review and meta-analysis. Eplasty 2011; 11:e38.
  18. de Vos RJ, Weir A, van Schie HT et al. Platelet-rich plasma injection for chronic Achilles tendinopathy: a randomized controlled trial. JAMA 2010; 303(2):144-9.
  19. Moraes VY, Lenza M, Tamaoki MJ et al. Platelet-rich therapies for musculoskeletal soft tissue injuries. Cochrane Database Syst Rev 2013; 12:CD010071.
  20. Kazakos K, Lyras DN, Verettas D et al. The use of autologous PRP gel as an aid in the management of acute trauma wounds. Injury 2009; 40(8):801-5.
  21. Nin JR, Gasque GM, Azcarate AV et al. Has platelet-rich plasma any role in anterior cruciate ligament allograft healing? Arthroscopy 2009; 25(11):1206-13.
  22. Griffin XL, Achten J, Parsons N et al. Platelet-rich therapy in the treatment of patients with hip fractures: a single centre, parallel group, participant-blinded, randomised controlled trial. BMJ Open 2013; 3(6).
  23. de Vos RJ, Windt J, Weir A. Strong evidence against platelet-rich plasma injections for chronic lateral epicondylar tendinopathy: a systematic review. Br J Sports Med 2014.
  24. Peerbooms JC, Sluimer J, Bruijn DJ et al. 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):255-62.
  25. Gosens T, Peerbooms JC, van Laar W et al. 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):1200-8.
  26. 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):463-71.
  27. Krogh TP, Fredberg U, Stengaard-Pedersen K et al. 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):625-35.
  28. Griffin XL, Wallace D, Parsons N et al. Platelet rich therapies for long bone healing in adults. Cochrane Database Syst Rev 2012; 7:CD009496.
  29. Calori GM, Tagliabue L, Gala L et al. Application of rhBMP-7 and platelet-rich plasma in the treatment of long bone non-unions: a prospective randomised clinical study on 120 patients. Injury 2008; 39(12):1391-402.
  30. Mei-Dan O, Carmont MR, Laver L et al. Platelet-rich plasma or hyaluronate in the management of osteochondral lesions of the talus. Am J Sports Med 2012; 40(3):534-41.
  31. Chang KV, Hung CY, Aliwarga F et al. Comparative Effectiveness of Platelet-Rich Plasma Injections for Treating Knee Joint Cartilage Degenerative Pathology: A Systematic Review and Meta-Analysis. Arch Phys Med Rehabil 2014; 95(3):562-75.
  32. Filardo G, Kon E, Di Martino A et al. Platelet-rich plasma vs hyaluronic acid to treat knee degenerative pathology: study design and preliminary results of a randomized controlled trial. BMC Musculoskelet Disord 2012; 13:229.
  33. Cerza F, Carni S, Carcangiu A et al. Comparison between hyaluronic acid and platelet-rich plasma, intra-articular infiltration in the treatment of gonarthrosis. Am J Sports Med 2012; 40(12):2822-7.
  34. Kon E, Buda R, Filardo G et al. Platelet-rich plasma: intra-articular knee injections produced favorable results on degenerative cartilage lesions. Knee Surg Sports Traumatol Arthrosc 2010; 18(4):472-9.
  35. de Almeida AM, Demange MK, Sobrado MF et al. Patellar tendon healing with platelet-rich plasma: a prospective randomized controlled trial. Am J Sports Med 2012; 40(6):1282-8.
  36. Monto RR. Platelet-Rich Plasma Efficacy Versus Corticosteroid Injection Treatment for Chronic Severe Plantar Fasciitis. Foot Ankle Int 2014.
  37. Castricini R, Longo UG, De Benedetto M et al. Platelet-rich plasma augmentation for arthroscopic rotator cuff repair: a randomized controlled trial. Am J Sports Med 2011; 39(2):258-65.
  38. Rodeo SA, Delos D, Williams RJ et al. The effect of platelet-rich fibrin matrix on rotator cuff tendon healing: a prospective, randomized clinical study. Am J Sports Med 2012; 40(6):1234-41.
  39. Weber SC, Kauffman JI, Parise C et al. Platelet-rich fibrin matrix in the management of arthroscopic repair of the rotator cuff: a prospective, randomized, double-blinded study. Am J Sports Med 2013; 41(2):263-70.
  40. Gumina S, Campagna V, Ferrazza G et al. Use of platelet-leukocyte membrane in arthroscopic repair of large rotator cuff tears: a prospective randomized study. J Bone Joint Surg Am 2012; 94(15):1345-52.
  41. Randelli P, Arrigoni P, Ragone V et al. Platelet rich plasma in arthroscopic rotator cuff repair: a prospective RCT study, 2-year follow-up. J Shoulder Elbow Surg 2011; 20(4):518-28.
  42. Rha DW, Park GY, Kim YK et al. Comparison of the therapeutic effects of ultrasound-guided platelet-rich plasma injection and dry needling in rotator cuff disease: a randomized controlled trial. Clin Rehabil 2013; 27(2):113-22.
  43. Carreon LY, Glassman SD, Anekstein Y et al. Platelet gel (AGF) fails to increase fusion rates in instrumented posterolateral fusions. Spine (Phila Pa 1976) 2005; 30(9):E243-6; discussion E47.
  44. Tsai CH, Hsu HC, Chen YJ et al. Using the growth factors-enriched platelet glue in spinal fusion and its efficiency. J Spinal Disord Tech 2009; 22(4):246-50.
  45. Everts PA, Devilee RJ, Brown Mahoney C et al. Exogenous application of platelet-leukocyte gel during open subacromial decompression contributes to improved patient outcome. A prospective randomized double-blind study. Eur Surg Res 2008; 40(2):203-10.
  46. Sidman JD, Lander TA, Finkelstein M. Platelet-rich plasma for pediatric tonsillectomy patients. Laryngoscope 2008; 118(10):1765-7.
  47. Almdahl SM, Veel T, Halvorsen P et al. Randomized prospective trial of saphenous vein harvest site infection after wound closure with and without topical application of autologous platelet-rich plasma. Eur J Cardiothorac Surg 2011; 39(1):44-8.
  48. American Academy of Orthopaedic Surgeons. Treatment of osteoarthritis of the knee. 2013. Available online at: http://www.aaos.org/research/guidelines/TreatmentofOsteoarthritisoftheKneeGuideline.pdf. Last accessed July, 2013.
  49. National Institute for Health and Clinical Evidence (NICE). Interventional Procedure Guidance 279: Autologous blood injection for tendinopathy. 2009. Available online at: http://www.nice.org.uk/nicemedia/pdf/IPG279Guidance.PDF. Last accessed April, 2014.
  50. National Institute for Health and Clinical Excellence. Autologous blood injection for plantar fasciitis. NICE interventional procedure guidance 437. 2013. Available online at: http://www.nice.org.uk/nicemedia/live/13883/62398/62398.pdf. Last accessed April 2014.
  51. CMS Manual System. Autologous blood-derived products for chronic non-healing wounds. CAG-00190R3. 2012. Available online at: http://www.cms.gov/medicare-coverage-database/details/nca-decision-memo.aspx?NCAId=260. Last accessed April, 2014
  52. CMS Manual System. Pub. 100-3 Medicare National Coverage Determinations, July 30, 2004.
  53. CMS Manual System. Decision memo on autologous blood derived products for chronic non-healing wounds. CAG-00190R2. 2008. Available online at: https://www.cms.hhs.gov/mcd/viewdecisionmemo.asp?id=208. Last accessed April, 2014.

Codes

Number

Description

CPT    See Policy Guidelines section 
ICD-9 Diagnosis  250.60 – 250.63  Diabetes with neurological manifestations code range. 
  250.80 – 250.83  Diabetes with other specified manifestations code range. 
  707.0  Decubitus ulcer 
  707.1  Ulcer of lower limbs, except decubitus 
  707.8  Chronic ulcer of other specified sites 
  707.9  Chronic ulcer of unspecified site 
  G0460 Autologous platelet rich plasma for chronic wounds/ulcers, including phlebotomy, centrifugation, and all other preparatory procedures, administration and dressings, per treatment
HCPCS P9020 Platelet rich plasma, each unit
  S0157  Becaplermin gel 0.01%, 0.5 gm 
  S9055  Procuren or other growth factor preparation to promote wound healing 
ICD-10-CM (effective 10/1/15) E11.40-E11.43 Diabetes with neurological manifestations code range
   E11.49 Diabetes with other diabetic neurological complication
   L89.000-L89.95 Pressure ulcer code range
   L97.121-L97.929 Pressure ulcer lowe limbs and foot code range
   L98.491-L98.499 Non pressure chronic ulcer of skin and other sites
ICD-10-PCS (effective 10/1/15)    ICD-10-PCS Codes are only for use on inpatient services. There is no specific ICD-10-PCS code for this procedure.
Type of Service  Medical 
Place of Service  Inpatient, outpatient, home 

 


Index

Autologel
Autologous platelet tissue graft
Becaplermin
GPSII
Growth Factors for Wound Healing
Magellan Autologous Platelet Separator
Platelet-rich Plasma
Regranex
Safeblood
Wound Healing, Growth Factors
 


Policy History
Date Action Reason
03/31/96 Add to Medicine section New policy
07/16/99 Replace policy Revised policy; addresses becaplermin gel
07/12/02 Replace policy Policy reviewed with changes: new policy statement on becaplermin gel for treatment of pressure ulcers
07/17/03 Replace policy Policy updated; no change in policy statement. Information regarding Autologel and Safeblood provided
11/9/04 Replace policy Policy updated; no change in policy statement. Reference added to Medicare national non-coverage policy for autologous platelet-derived products for chronic non- healing wounds
09/27/05 Replace policy Policy revised; policy statement added regarding miscellaneous use of platelet-rich plasma as a primary procedure. Description and rationale now include discussion of platelet-rich plasma. Reference numbers 4 through 7 added.
04/17/07 Replace policy Policy updated with literature search; reference numbers 9-12 added; policy statement unchanged 
07/10/08 Replace policy  Policy updated with literature search; references reordered; policy statements unchanged
08/13/09 Replace policy Policy updated with literature search through June 2009; references added and reordered; acute wounds added for PRP, other policy statements unchanged
11/12/09 Replace policy Policy updated with literature search through September 2009; references 10, 15-21 added. PRP as an adjunct to surgical procedures added as investigational; other policy statements unchanged
4/14/11 Replace policy Policy updated with literature search, reference numbers 11-14, 18, 19, 23, 24 added, policy statements unchanged
04/12/12 Replace policy Policy updated with literature search through February 2012, references added and reordered; some references removed; policy statements unchanged
04/11/13 Replace policy Policy updated with literature search through March 8, 2013; references added and reordered; policy statements unchanged
5/22/14 Replace policy Policy updated with literature review through March 25, 2014; references 6, 19, 22-23, 26, 31, 36, and 48 added and reordered; policy statements unchanged