mp-241 - Medical Policies - Alabama
Recombinant and Autologous Platelet-Derived Growth Factors for Wound Healing, Orthopedic Applications, and Other Non-Orthopedic Conditions
Policy Number: MP-241
Latest Review Date: April 2021
Policy Grade: C
Recombinant platelet-derived growth factor (i.e., becaplermin) may be considered medically necessary when used as an adjunct to standard wound management for the following indications:
- Neuropathic diabetic ulcers extending into the subcutaneous tissue when all of the following criteria is met:
- 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); AND
- Full thickness ulcer (i.e., stage III or IV), extending through dermis into subcutaneous tissues; AND
- Participation in a wound-management program, which includes sharp debridement, pressure relief, and infection control
- Pressure ulcers extending into the subcutaneous tissue when all of the following criteria is met:
- Full-thickness ulcer (stage III or IV), extending through dermis into the subcutaneous tissue; AND
- Ulcer in an anatomic location that can be off-loaded for the duration of treatment; AND
- Albumin concentration > 2.5 dL; AND
- Total lymphocyte count > 1,000; AND
- Normal values of vitamins A and C
Treatments are normally for 20 weeks or complete healing.
Other applications of recombinant platelet-derived growth factor (i.e., becaplermin) are considered not medically necessary and investigational, including, but not limited to, ischemic ulcers, ulcers related to venous stasis, and ulcers not extending through the dermis into the subcutaneous tissue.
Autologous blood derived preparations (i.e., platelet rich plasma) are considered not medically and investigational, including but not limited to, use in the following:
- Treatment of acute or chronic wounds including surgical wounds, and non-healing ulcers
- All orthopedic indications including but not limited to the following situations and conditions:
- Primary use (injection)
- Achilles tendinopathy
- Lateral epicondylitis
- Plantar fasciitis
- Osteochondral lesions
- Dupuytren’s contracture
- Cartilage degeneration
- Degenerative disc disease
- Adjunctive use in surgical procedures
- ACL reconstruction
- Hip fracture
- Long-bone nonunion
- Patellar tendon repair
- Rotator cuff repair
- Spinal fusion
- Subacromial decompression surgery
- Total knee arthroplasty
DESCRIPTION OF PROCEDURE OR SERVICE:
This policy addresses the use of blood-derived growth factors, including recombinant platelet- derived growth factors (PDGFs) and platelet-rich plasma (PRP), as a treatment of wounds or other miscellaneous non‒orthopedic conditions, including but not limited to treatment of diabetic ulcers, pressure ulcers, and ulcers related to venous stasis.
A variety of growth factors have been found to play a role in wound healing, including platelet-derived growth factors, 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 platelet-rich plasma (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 various tissues. PRP injections have been proposed as a primary treatment of miscellaneous conditions, such as epicondylitis, plantar fasciitis, and Dupuytren contracture.
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.
Wound Closure Outcomes
This policy addresses the use of recombinant PDGF products and PRP for non-orthopedic indications, which include a number of wound closure-related indications.
For the purposes of this review, the primary end points of interest for studies of wound closure are as follows, consistent with guidance from the FDA for industry in developing products for treatment of chronic cutaneous ulcer and burn wounds:
- Incidence of complete wound closure.
- Time to complete wound closure (reflecting accelerated wound closure).
- Incidence of complete wound closure following surgical wound closure.
- Pain control.
The most recent literature update was performed through March 5, 2021.
Summary of Evidence
The evidence for recombinant PDGF in individuals who have diabetic lower-extremity ulcers or pressure ulcers includes randomized controlled trials (RCTs) and systematic reviews. Relevant outcomes are symptoms, change in disease status, morbid events, quality of life, and treatment-related morbidity. Results show improved rates of healing with use of recombinant PDGF for diabetic neuropathic ulcers and pressure ulcers. The evidence is sufficient to determine qualitatively that the technology results in a meaningful improvement in the net health outcome.
The evidence for recombinant PDGF in individuals who have venous ulcers or traumatic wounds includes small RCTs. Relevant outcomes are symptoms, change in disease status, morbid events, quality of life, and treatment-related morbidity. It cannot be determined whether recombinant PDGF is effective to treat other wound types, including chronic venous ulcers or acute traumatic wounds. The evidence is insufficient to determine the effects of the technology on health outcomes.
The evidence for PRP in individuals who have chronic wounds or acute surgical or traumatic wounds includes a number of small controlled trials. Relevant outcomes are symptoms, change in disease status, morbid events, quality of life, and treatment-related morbidity. The potential benefit of PRP has received considerable interest due to its appeal as a simple, safe, low-cost, and minimally invasive method of applying growth factors. Current results of trials using PRP are mixed and the studies are limited in both size and quality. The evidence is insufficient to determine the effects of the technology on health outcomes.
Primary Treatment for Tendinopathies
For individuals with tendinopathy who receive PRP injections, the evidence includes multiple randomized controlled trials (RCTs) and systematic reviews with meta-analyses. Relevant outcomes are symptoms, functional outcomes, health status measures, quality of life, and treatment-related morbidity. Findings from meta-analyses of RCTs have been mixed and have generally found that PRP did not have a statistically and/or clinically significant impact on symptoms (ie, pain) or functional outcomes.Findings from subsequently published RCTs have also been mixed. 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 effects of the technology on health outcomes.
Primary Treatment for Non‒Tendon Soft Tissue Injury or Inflammation
For individuals with non-tendon soft tissue injury or inflammation (e.g., plantar fasciitis) who receive PRP injections, the evidence includes six small RCTs, multiple prospective observational studies, and a systematic review. The relevant outcomes are symptoms, functional outcomes, health status measures, QOL, and treatment-related morbidity. The systematic review, which identified three RCTs on PRP for plantar fasciitis, did not pool study findings. Results among the six RCTs were inconsistent. The largest RCT showed that treatment using PRP compared with corticosteroid injection resulted in statistically mprovement in pain and disability, but not quality of life. The evidence is insufficient to determine the effects of the technology on health outcomes.
Primary Treatment for Osteochondral Lesions
For individuals with osteochondral lesions who receive PRP injections, the evidence includes an open-labeled quasi-randomized study. Relevant outcomes are symptoms, functional outcomes, health status measures, quality of life, and treatment-related morbidity. The quasi-randomized study found a statistically significant greater impact on outcomes in the PRP group than in the group receiving hyaluronic acid. Limitations of the evidence base include lack of adequately randomized studies, lack of blinding, lack of sham controls, and comparison only to an intervention of uncertain efficacy. The evidence is insufficient to determine the effects of the technology on health outcomes.
Primary Treatment for Knee or Hip Osteoarthritis
For individuals with knee or hip OA who receive PRP injections, the evidence includes multiple RCTs and systematic reviews. The relevant outcomes are symptoms, functional outcomes, health status measures, QOL, and treatment-related morbidity. Most trials have compared PRP with hyaluronic acid for knee OA. Systematic reviews have generally found that PRP was more effective than placebo or hyaluronic acid 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 residual statistical heterogeneity, questionable clinical significance, and high risk of bias in study conduct. RCTs with followup durations of at least 12 months published subsequent to the systematic reviews found statistically significantly greater 12-month reductions in WOMAC scores, but these findings were also limited by important study conduct flaws including potential inadequate control for selection bias and unclear blinding. Also, benefits were not maintained at 5 yearsAlso, using hyaluronic acid as a comparator is questionable, because the evidence demonstrating the benefit of hyaluronic acid treatment for OA is not robust. The single RCT evaluating hip OA reported statistically significant reductions in VAS scores for pain, with no difference in functional scores. Additional studies comparing PRP with placebo and with alternatives other than hyaluronic acid are needed to determine the efficacy of PRP for knee and hip OA. Studies are also needed to determine the optimal protocol for delivering PRP. The evidence is insufficient to determine the effects of the technology on health outcomes.
Adjunct to Surgery
For individuals with anterior cruciate ligament reconstruction who receive PRP injections, the evidence includes 2 systematic reviews of multiple RCTs and prospective studies. Relevant outcomes are symptoms, functional outcomes, health status measures, quality of life, morbid events, resource utilization, and treatment-related morbidity. Only 1 of the 2 systematic reviews conducted a meta-analysis; it showed that adjunctive PRP treatment did not result in significant effect on International Knee Documentation Committee scores, a patient-reported, knee-specific outcome measure that assesses pain and functional activity. Individual trials have shown mixed results. The evidence is insufficient to determine the effects of the technology on health outcomes.
For individuals with hip fracture who receive PRP injections, the evidence includes 1 open-labeled RCT. Relevant outcomes are symptoms, functional outcomes, health status measures, quality of life, morbid events, resource utilization, and treatment-related morbidity. The single open-labeled RCT failed to show any statistically significant reduction in the need for surgical revision with the addition of PRP treatment. The evidence is insufficient to determine the effects of the technology on health outcomes.
For individuals with long bone nonunion who receive PRP injections plus orthopedic surgery, the evidence includes three RCTs. The relevant outcomes are symptoms, functional outcomes, health status measures, QOL, morbid events, resource utilization, and treatment-related morbidity. One trial with a substantial risk of bias failed to show significant differences in patient-reported or clinician-assessed functional outcome scores between those who received PRP plus allogenic bone graft and those who received only allogenic bone graft. While the trial showed a statistically significant increase in the proportion of bones that healed in patients receiving PRP in a modified intention-to-treat analysis, the results did not differ in the intention-to-treat analysis. The second RCT, which compared PRP with rhBMP-7, also failed to show any clinical or radiologic benefits of PRP over morphogenetic protein. The third RCT reported no difference in the number of unions or time to union in patients receiving PRP injections s no treatment. The evidence is insufficient to determine the effects of the technology on health outcomes.
For individuals with rotator cuff repair who receive PRP injections plus orthopedic surgery, the evidence includes multiple RCTs and systematic reviews. The relevant outcomes are symptoms, functional outcomes, health status measures, QOL, morbid events, resource utilization, and treatment-related morbidity. Although systematic reviews consistently found significant reductions in pain with PRP at 12 months, important study conduct and relevance weaknesses limit interpretation of these findings. Additionally, the pain reductions with PRP were not maintained in longer-term studies. Further, the systematic reviews and meta- analyses failed to show a statistically and/or clinically significant impact on other outcomes. Findings of subsequently published small, single-center RCTs were consistent with the systematic reviews. The evidence is insufficient to determine the effects of the technology on health outcomes.
For individuals with spinal fusion who receive PRP injections plus orthopedic surgery, the evidence includes two controlled prospective studies. The relevant outcomes are symptoms, functional outcomes, health status measures, QOL, morbid events, resource utilization, and treatment-related morbidity. The two studies failed to show any statistically significant differences in fusion rates between the PRP arm and the control arm. The evidence is insufficient to determine the effects of the technology on health outcomes.
For individuals undergoing spinal fusion who receive PRP injections, the evidence includes a single small RCT and a few observational studies. Relevant outcomes include symptoms, functional outcomes, health status measures, quality of life, morbid events, resource utilization, and treatmentrelated morbidity. Studies have generally failed to show a statistically and/or clinically significant impact on symptoms (ie, pain). The evidence is insufficient to determine the effects of the technology on health outcomes.
For individuals with subacromial decompression surgery who receive PRP injections, the evidence includes 1 small RCT. Relevant outcomes are symptoms, functional outcomes, health status measures, quality of life, morbid events, resource utilization, and treatment-related morbidity. A single small RCT failed to show reduced self-assessed or physician-assessed spinal instability with PRP injections. However, subjective pain, use of pain medications, and objective measures of range of motion showed clinically significant improvements with PRP. Larger trials are required to confirm these benefits. The evidence is insufficient to determine the effects of the technology on health outcomes.
For individuals with total knee arthroplasty who receive PRP injections, the evidence includes 1 small RCT. Relevant outcomes are symptoms, functional outcomes, health status measures, quality of life, morbid events, resource utilization, and treatment-related morbidity. The RCT showed no significant differences between the PRP and untreated control groups in terms of bleeding, range of motion, swelling around the knee joint, muscle power recovery, pain, or Knee Society Score and Knee Injury and Osteoarthritis Outcome Score. The evidence is insufficient to determine the effects of the technology on health outcomes.
Practice Guidelines And Position Statements
American College of Physicians
In 2015, the American College of Physicians (ACP) published guidelines on treatment of pressure ulcers. The guidelines noted that “although low quality evidence suggests that dressings containing PDGF [platelet-derived growth factors] promote healing, ACP supports the use of other dressings such as hydrocolloid and foam dressings, which are effective at promoting healing and cost less than PDGF dressings.”
Association for the Advancement of Wound Care
In 2010, the Association for the Advancement of Wound Care developed guidelines pressure ulcers and on venous ulcer:
- Pressure ulcer: growth factors are not indicated at this time (level C evidence – no RCTs available comparing growth factors with A-level dressings)
- Venous ulcer: platelet derived growth factor has shown no significant effects on venous ulcer healing or recurrence (level A evidence).
National Institute for Health and Care Excellence
In January 2016, NICE updated its guidance on the prevention and management of diabetic foot problems. The guidance states that neither autologous platelet-rich plasma gel nor platelet-derived growth factor should be offered in the treatment of diabetic foot ulcers.
American Academy of Orthopaedic Surgeons
The 2013 American Academy of Orthopaedic Surgeons (AAOS) guidelines were unable to recommend for or against growth factor injections and/or platelet-rich plasma (PRP) for patients with symptomatic osteoarthritis of the knee. A recommendation of inconclusive was based on a single low-quality study and conflicting findings that did not permit a recommendation for or against the intervention. The AAOS recommendation as based on 3 studies published before May 2012.
National Institute for Health and Care Excellence
In 2013, the U.K.’s National Institute for Health and Care Excellence (NICE) issued guidance on use of autologous blood injection for tendinopathy. NICE concluded that the current evidence on the safety and efficacy of autologous blood injection for tendinopathy is “inadequate” in quantity and quality. NICE recommended “this procedure should only be used with special arrangements for clinical governance, consent, and audit or research.”
In 2013, NICE also issued guidance on use of autologous blood injection (with or without techniques for producing PRP) for plantar fasciitis. NICE concluded that the evidence on autologous blood injection for plantar fasciitis raised no major safety concerns but that the evidence on efficacy was “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.”
In 2019, the NICE issued guidance on the use of PRP for OA of the knee. The NICE concluded that current evidence on PRP injections for OA of the knee raised “no major safety concerns”;however, the “evidence on efficacy is limited in quality. Therefore, NICE recommended that "this procedure should only be used with special arrangements for clinical governance, consent, and audit or research."
U.S. Preventive Services Task Force Recommendations
Autologous platelet derived growth factors, autologous blood derived preparations, platelet-derived growth factors, PDGF, platelet rich plasma, PRP, autologous platelet gel, Autologel, SafeBlood, Medtronic Electromedic, Elmd-500 Autotransfusion system, Plasma Saver, Smart PreP, wound healing, platelet gel, platelet concentrate, autologous blood-derived products, platelet-derived wound healing formulas, epicondylitis, tennis elbow, plantar fasciitis, Dupuytren’s contracture, becaplermin, becaplermin gel, recombinant platelet-derived growth factor
APPROVED BY GOVERNING BODIES:
In 1997, becaplermin gel (Regranex®, Smith & Nephew), a recombinant platelet-derived growth factor (PDGF) product, was approved by the U.S. Food and Drug Administration (FDA) for the following labeled indication:
"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 debridement, 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 three 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.”
The U.S. Food and Drug Administration regulates human cells and tissues intended for implantation, transplantation, or infusion through the Center for Biologics Evaluation and Research, under Code of Federal Regulation (CFR) title 21, parts 1270 and 1271. Blood products such as platelet-rich plasma are included in these regulations. Under these regulations, certain products including blood products such as PRP are exempt and therefore, do not follow the traditional FDA regulatory pathway. To date, FDA has not attempted to regulate activated PRP.
A number of PRP preparation systems are available, many of which were cleared for marketing by FDA through the 510(k) process for producing platelet-rich preparations intended to be mixed with bone graft materials to enhance the bone grafting properties in orthopedic practices. The Aurix System™ (previously called AutoloGel™; Cytomedix) and SafeBlood® (SafeBlood Technologies) are 2 related but distinct autologous blood-derived preparations that can be used 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 (eg, Medtronic Electromedics, Elmd-500 Autotransfusion system, the Plasma Saver device, the SmartPReP® [Harvest Technologies] device). The Magellan™ Autologous Platelet Separator System (Medtronic Sofamor Danek) includes a disposables kit for use with the Magellan™ Autologous Platelet Separator portable tabletop centrifuge. GPS®II (BioMet Biologics), a gravitational platelet separation system, was cleared for marketing by FDA through the 510(k) process for use as 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.
In 2018, the “Boxed Warning” and “Warnings and Precautions” were changed to remove “increased rate of cancer mortality” and “cancer mortality,” respectively.
Coverage is subject to member’s specific benefits. Group specific policy will supersede this policy when applicable.
ITS: Home Policy provisions apply
FEP contracts: Special benefit consideration may apply. Refer to member’s benefit plan. FEP does not consider investigational if FDA approved and will be reviewed for medical necessity.
Injection(s) platelet rich plasma, any tissue, including image guidance, harvesting and preparation when performed
Injection(s), autologous white blood cell concentrate (autologous protein solution), any site, including image guidance, harvesting and preparation, when performed
Unlisted procedure, spine
Unlisted procedure, femur or knee
Unlisted procedure, arthroscopy
Unlisted procedure, dentoalveolar structures
Unlisted transfusion medicine procedure
NOTE: CPT code 20926-Tissue graft, other (DELETED 12/31/19) should not be billed for application of recombinant and autologous platelet derived growth factors.
Collection and application of autologous blood concentrate product
Autologous platelet rich plasma for chronic wounds/ulcers, including phlebotomy, centrifugation, and all other preparatory procedures, administration and dressings, per treatment
Platelet rich plasma, each unit
Becaplermin gel 0.01%, 0.5gm
Procuren or other growth factor preparation to promote wound healing
- Ahmed M, Reffat SA, Hassan A, et al. Platelet-Rich Plasma for the Treatment of Clean Diabetic Foot Ulcers. Ann Vasc Surg. Jan 2017; 38: 206-211.
- Alamdari DH AM, Rahim AN, et al. Efficacy and Safety of Pleurodesis Using Platelet-Rich Plasma and Fibrin Glue in Management of Postoperative Chylothorax After Esophagectomy. World J Surg. 2018;42(4):1046-1055.
- 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):44-48.
- American Academy of Orthopaedic Surgeons A. Management of Osteoarthritis of the Hip - Evidence-Based Clinical Practice Guideline. 2017; https://www.aaos.org/uploadedFiles/PreProduction/Quality/Guidelines_and_Reviews/OA%20Hip%20CPG_1.5.1 8.pdf. Accessed February 15, 2018.
- American Academy of Orthopaedic Surgeons. Treatment of osteoarthritis of the knee. 2013. Available online at: www.aaos.org/research/guidelines/TreatmentofOsteoarthritisoftheKneeGuideline.pdf.
- American Medical Association. Coding consultation: questions and answers. CPT® Assistant 2005; 15(11):14.
- Andia I, Latorre PM, Gomez MC, et al. Platelet-rich plasma in the conservative treatment of painful tendinopathy: a systematic review and meta-analysis of controlled studies. Br Med Bull. Jun 2014; 110(1):99-115.
- Association for the Advancement of Wound Care (AAWC). AAWC Guideline: Pressure Ulcer. //aawconline.org/wpcontent/uploads/2015/11/AAWCPressureUlcerGuidelineofGuidelinesAug11.pdf. Accessed December 12, 2016.
- Association for the Advancement of Wound Care (AAWC). AAWC Venous Ulcer Guideline. //aawconline.org/wp-content/uploads/2015/11/AAWC-Venous-Ulcer-Guideline-Update-Algorithm-v28-updated-11Feb2014.pdf. Accessed December 12, 2016.
- Balasubramaniam U, Dissanayake R, Annabell L. Efficacy of platelet-rich plasma injections in pain associated with chronic tendinopathy: a systematic review. Phys Sportsmed. Jul 2015; 43(3):253-261.
- Barrett S and Erredge S. Growth factors for chronic plantar fascitis. Podiatry Today 2004; 17:37-42.
- Beitzel K, Allen D, Apostolakos J, et al. US definitions, current use, and FDA stance on the use of platelet-rich plasma in sports medicine. J Knee Surg Feb 2015; 28(1):29-34.
- Best TM, Zgierska AE, et al. A systematic review of four injection therapies for lateral epicondylosis: Prolotherapy, polidocanol, whole blood and platelet rich plasma. Br J Sports Med, July 2009; 43(7): 471-481.
- Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Becaplermin for wound healing. TEC Assessments 1999; Volume 14, Tab 5.
- Blue Cross and Blue Shield Association Technology Evaluation Center. Growth factors for wound healing. TEC Evaluations 1999 7:352-377.
- Cai YZ, Zhang C, Lin XJ. Efficacy of platelet-rich plasma in arthroscopic repair of full-thickness rotator cuff tears: a meta-analysis. J Shoulder Elbow Surg. Dec 2015; 24(12):1852-1859.
- Calori GM, Tagliabue L, et al. Application of rhBMP-7 and platelet-rich plasma in the treatment of long bone non-unions: a prospective randomized clinical study on 120 patients. Injury, Dec 2008; 39(12): 1391-1402.
- Carlson NE, Roach RB Jr. Platelet-rich plasma: clinical applications in dentistry. J Am Dent Assoc 2002; 133(10):1383-6.
- Carreon LY, Glassman SD, et al. Platelet gel (AGF) fails to increase fusion rates in instrumented posterolateral fusions. Spine, May 2005; 30(9): E243-E246; discussion E247.
- 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.
- Castillo TN, Pouliot MA, Kim HJ et al. Comparison of growth factor and platelet concentration from commercial platelet-rich plasma separation systems. Am J Sports Med Feb 2011; 39(2):266-271.
- 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):258-265.
- Centers for Medicare & Medicaid Services (CMS). CMS Manual System: Pub 100-3 Medicare National Coverage Determinations (Transmittal 127). 2010 Oct; https://www.cms.gov/Regulations-and-Guidance/Guidance/Transmittals/downloads/R127NCD.pdf. Accessed November 21, 2019.
- Centers for Medicare & Medicaid Services. Decision Memo for Autologous Blood-Derived Products for Chronic Non-Healing Wounds (CAG-00190R3). 2012; https://www.cms.gov/medicare-coverage-database/details/nca-decision-memo.aspx?NCAId=260. Accessed December 23, 2019
- Centers for Medicare & Medicaid Services. Decision Memo for Autologous Blood Derived Products for Chronic Non-Healing Wounds (CAG-00190R2). 2008; https://www.cms.gov/medicare-coverage-database/details/nca-decision-memo.aspx? NCAId=208&bc=ACAAAAAAQCAA&. Accessed November 21, 2019.
- 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):2822-2827.
- 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):562-575.
- Chen HY, Chen CX, Liang Y, Wang J. Efficacy of autologous platelet richgel in the treatment of refractory diabetic foot. Chin J New Clin Med. 2008;17:1-2.
- Chen X, Jones IA, Togashi R, et al. 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. Jul 2020; 48(8): 2028-2041.
- Chen X, Jones IA, Park C, et al. The efficacy of platelet-rich plasma on tendon and ligament healing: a systematic review and meta-analysis with bias assessment. Am J Sports Med. Dec 1 2017:363546517743746.
- Chen W, Lo WC, Lee JJ, Su Ch, et al. Tissue engineered intervertebral disc and chondrogenesis using human nucleus pulposus regulated through TGF-beta 1 in platelet-rich plasma. J Cell Physiol. 2006; 2009(3):744.54.
- Cole BJ, Karas V, Hussey K, et al. Hyaluronic acid versus platelet-rich plasma. Am J Sports Med. Feb 2017; 45(2):339-346.
- Crovetti G, Martinelli G, et al. Platelet gel for healing cutaneous chronic wounds. Transfus Apheresis Sci Apr 2004; 30:145-151.
- Dallari D, Savarino L, Stagni C, et al. Enhanced tibial osteotomy healing with use of bone grafts supplemented with platelet gel or platelet gel and bone marrow stromal cells. J Bone Joint Surg Am. Nov 2007;89(11):2413- 2420.
- Dallari D, Stagni C, Rani N, et al. Ultrasound-guided injection of platelet-rich plasma and hyaluronic acid, separately and in combination, for hip osteoarthritis: a randomized controlled study. Am J Sports Med. Mar 2016;44(3):664-671.
- 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. Jun 2012; 40(6):1282-8.
- 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.
- 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):144-149.
- 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.
- Del Pino-Sedeno T, Trujillo-Martin MM, Andia I, et al. Platelet-rich plasma for the treatment of diabetic foot ulcers: A meta-analysis. Wound Repair Regen, 2018 Dec 24;27(2).
- 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):1184-1192.
- Di Martino A, Di Matteo B, Papio T et al. Platelet-Rich Plasma Versus Hyaluronic Acid Injections for the Treatment of Knee Osteoarthritis: Results at 5 Years of a Double-Blind, Randomized Controlled Trial. Am J Sports Med. 2019 Feb;47(2).
- Driver VR, Hanft J, Fylling CP, Beriou JM, et al. A prospective, randomized, controlled trial of autologous platelet-rich plasma gel for the treatment of diabetic foot ulcers. Ostomy Wound Manage, June 2006; 52(6): 68-70, 72, 74. (Abstract)
- Duymus TM, Mutlu S, Dernek B, et al. Choice of intra-articular injection in treatment of knee osteoarthritis: platelet-rich plasma, hyaluronic acid or ozone options. Knee Surg Sports Traumatol Arthrosc. Feb 2017; 25(2):485-492.
- Ebert JR, Wang A, Smith A, et al. A midterm evaluation of postoperative platelet-rich plasma injections on arthroscopic supraspinatus repair: a randomized controlled trial. Am J Sports Med. Nov 2017;45(13):2965-2974.
- El-Anwar MW, Nofal AA, Khalifa M, et al. Use of autologous platelet-rich plasma in complete cleft palate repair. Laryngoscope. Jul 2016; 126(7):1524-1528.
- Elksnins-Finogejevs A, Vidal L, Peredistijs A. Intra-articular platelet-rich plasma vs corticosteroids in the treatment of moderate knee osteoarthritis: a single-center prospective randomized controlled study with a 1-year follow up. J Orthop Surg Res. Jul 10 2020; 15(1): 257.
- Elsaid A, El-Said M, Emile S, et al. Randomized Controlled Trial on Autologous Platelet-Rich Plasma Versus Saline Dressing in Treatment of Non-healing Diabetic Foot Ulcers. World J Surg. Apr 2020; 44(4): 1294-1301.
- Eppley BL, Woodell JE, Higgins J. Platelet quantification and growth factor analysis from platelet-rich plasma: implications for wound healing. Plast Reconstr Surg. Nov 2004(6); 114; 1502-1508.
- Escamilla Cardenosa M, Dominguez-Maldonado G, Cordoba-Fernandez A. Efficacy and safety of the use of platelet-rich plasma to manage venous ulcers. J Tissue Viability. Nov 29 2016.
- Everts PA, Devilee RJ, 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): 203-210.
- Figueroa D, Figueroa F, Calvo R, et al. Platelet-rich plasma use in anterior cruciate ligament surgery: systematic review of the literature. Arthroscopy. May 2015; 31(5):981-988.
- 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.
- Fitzpatrick J, Bulsara MK, O'Donnell J et al. Leucocyte-Rich Platelet-Rich Plasma Treatment of Gluteus Medius and Minimus Tendinopathy: A Double-Blind Randomized Controlled Trial With 2-Year Follow-up. Am J Sports Med. 2019 Apr;47(5).
- Floryan KM. Intraoperative use of autologous platelet-rich and platelet-poor plasma for orthopedic surgery patients. J AORN 2004.
- Franceschi F, Papalia R, Franceschetti E, et al. Platelet-rich plasma injections for chronic plantar fasciopathy: a systematic review. Br Med Bull. Dec 2014; 112(1):83-95.
- Frechette JP, Martineau I, Gagnon G. Platelet-rich plasma: Growth factor content and roles in wound healing. J Dent Res 2005; 84(5):434-439.
- Freedman BM, Oplinger EH and Freedman IS. Topical becaplermin improves outcomes in work related fingertip injuries. J Trauma, October 2005; 59(4): 965-968.
- Friese G, Herten M, Scherbaum WA. The use of autologous platelet concentrate activated by autologous thrombin (APC+) is effective and safe in the treatment of chronic diabetic foot ulcers-a randomized controlled trial. In: eds. Proceedings of the Fifth International Symposium on the Diabetic Foot, May September 12, 2007, Noordwijkerhout, The Netherlands. 2007.
- Fu CJ, Sun JB, Bi ZG, et al. Evaluation of platelet-rich plasma and fibrin matrix to assist in healing and repair of rotator cuff injuries: a systematic review and meta-analysis. Clin Rehabil. Feb 2017;31(2):158-172.
- Game F, Jeffcoate W, Tarnow L, et al. LeucoPatch system for the management of hard-to-heal diabetic foot ulcers in the UK, Denmark, and Sweden: an observer-masked, randomised controlled trial. Lancet Diabetes Endocrinol. Nov 2018; 6(11): 870-878.
- Gibbs S, van den Hoogenband HM, Kirtschig G, et al. Autologous full-thickness skin substitute for healing chronic wounds. Br J Dermatol, August 2006; 155(2): 267-274. (Abstract)
- 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):1200-1208.
- 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).
- Griffin XL, Wallace D, Parsons N et al. Platelet rich therapies for long bone healing in adults. Cochrane Database Syst Rev 2012; 7:CD009496.
- Gude W, Hagan D, Abood F, et al. Aurix Gel Is an Effective Intervention for Chronic Diabetic Foot Ulcers: A Pragmatic Randomized Controlled Trial. Adv Skin Wound Care. Sep 2019; 32(9): 416-426.
- 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):1345-1352.
- Gupta PK, Acharya A, Khanna V et al. PRP versus steroids in a deadlock for efficacy: long-term stability versus short-term intensityresults from a randomised trial. Musculoskelet Surg. 2019 Aug.
- Huang Y, Liu X, Xu X et al. Intra-articular injections of platelet-rich plasma, hyaluronic acid or corticosteroids for knee osteoarthritis : A prospective randomized controlled study. Orthopade. 2019 Mar;48(3).
- Hsu WK, Mishra A, Rodeo SR, et al. Platelet-rich plasma in orthopaedic applications: evidence-based recommendations for treatment. J Am Acad Orthop Surg. Dec 2013; 21(12):739-748.
- Johal H, Khan M, Yung SP et al. Impact of Platelet-Rich Plasma Use on Pain in Orthopaedic Surgery: A Systematic Review and Metaanalysis. Sports Health. 2019 Jul;11(4).
- 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 Spec. 2019 Apr;12(2).
- Kakagia DD, Kazakos KJ, Xarchas KC, et al. Synergistic action of protease-modulating matrix and autologous growth factors in healing of diabetic foot ulcers. A prospective randomized trial. J Diabetes Complications. Nov-Dec 2007; 21(6): 387-91.
- Kanchanatawan W, Arirachakaran A, Chaijenkij K, et al. Short-term outcomes of platelet-rich plasma injection for treatment of osteoarthritis of the knee. Knee Surg Sports Traumatol Arthrosc. May 2016; 24(5):1665-1677.
- Karimi R, Afshar M, Salimian M, et al. The effect of platelet rich plasma dressing on healing diabetic foot ulcers. Nurs Midwifery Stud. 2016;5(3):e30314.
- Kazakos K, Lyras DN, et al. The use of autologous PRP gel as an aid in the management of acute trauma wounds. Injury, August 2009; 40(8): 801-805.
- Kevy SV, Jacobson MS. Comparison of methods for point of care preparation of autologous platelet gel. JECT Mar 2004; 36:28-35.
- Knox RL, Hunt AR, Collins JC, et al. Platelet-rich plasma combined with skin substitute for chronic wound healing: a case report. J Extra Corpor Technol, Sept 2006; 38(3): 260-264. (Abstract)
- 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, April 2010; 18(4): 472-479.
- 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):625-635.
- Kubota G, Kamoda H, Orita S et al. Platelet-rich plasma enhances bone union in posterolateral lumbar fusion: A prospective randomized controlled trial. Spine J. 2019 Feb;19(2).
- Lai LP, Stitik TP, Foye PM, et al. Use of platelet-rich plasma in intra-articular knee injections for osteoarthritis: a systematic review. PMR. Jun 2015; 7(6):637-648.
- Laudy AB, Bakker EW, Rekers M, et al. Efficacy of platelet-rich plasma injections in osteoarthritis of the knee: a systematic review and meta-analysis. Br J Sports Med. May 2015; 49(10):657-672.
- Li L, Chen D, Wang C, et al. Autologous platelet-rich gel for treatment of diabetic chronic refractory cutaneous ulcers: A prospective, randomized clinical trial. Wound Repair Regen. Jul-Aug 2015; 23(4): 495-505.
- Li Y, Gao Y, Gao Y, et al. Autologous platelet-rich gel treatment for diabetic chronic cutaneous ulcers: A meta-analysis of randomized controlled trials.. J Diabetes, 2018 Sep 6;11(5).
- Lin KY, Yang CC, Hsu CJ et al. 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 Jan;35(1).
- Liu GY, Deng XL, Sun Y, Wang MZ, Gao J, Gou J. Effect of autologous platelet-rich gel on the treatment of diabetic foot ulcers. J Xi'an Jiaotong Univ (Med Sci). 2016;37:264-267.
- Ma L. Clinical efficacy of autologous platelet rich gel in the treatment of diabetic foot and diabetic chronic cutaneous ulcer. Chin J Mod Drug Appl.2014;8:86-88
- Malavolta EA, Gracitelli MEC, Assuncao JH, et al. Clinical and structural evaluations of rotator cuff repair with and without added platelet-rich plasma at 5-year follow-up: A prospective randomized study. Am J Sports Med. Nov 2018;46(13):3134-3141.
- Marck RE, Gardien KL, Stekelenburg CM, et al. The application of platelet-rich plasma in the treatment of deep dermal burns: A randomized, double-blind, intra-patient controlled study. Wound Repair Regen. Jul 2016; 24(4):712-720.
- 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, Nov-Dec 2005; 13(6): 531-536.
- Martin JI, Atilano L, Bully P et al. Needle tenotomy with PRP versus lidocaine in epicondylopathy: clinical and ultrasonographic outcomes over twenty months. Skeletal Radiol. 2019 Sep;48(9) .
- Martinez-Zapata MJ, Marti-Carvajal A, et al. Efficacy and safety of the use of autologous plasma rick in platelets for tissue regeneration: a systematic review. Transfusion, January 2009; 49(1): 44-56.
- Martinez-Zapata MJ, Marti-Carvajal AJ, Sola I et al. Autologous platelet-rich plasma for treating chronic wounds. Cochrane Database Syst Rev 2012; 10:CD006899.
- Martinez-Zapata MJ, Marti-Carvajal AJ, Sola I, et al. Autologous platelet-rich plasma for treating chronic wounds. Cochrane Database Syst Rev. May 25 2016(5):CD006899.
- 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. Aug 2009; 97(2):110-118.
- Meheux CJ, McCulloch PC, Lintner DM, et al. Efficacy of intra-articular platelet-rich plasma injections in knee osteoarthritis: a systematic review. Arthroscopy. Mar 2016; 32(3):495-505.
- 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. Mar 2012; 40(3):534-541.
- Milek T, Baranowski K, Zydlewski P, et al. Role of plasma growth factor in the healing of chronic ulcers of the lower legs and foot due to ischaemia in diabetic patients. Postepy Dermatol Alergol. Dec 2017; 34(6): 601-606.
- Miller LE, Parrish WR, Roides B, et al. Efficacy of platelet-rich plasma injections for symptomatic tendinopathy: systematic review and meta-analysis of randomised injection-controlled trials. BMJ Open Sport Exerc Med. Nov 6 2017;3(1):e000237.
- Mishra AK, Pavelko T. Treatment of chronic elbow tendinosis with buffered platelet-rich plasma. Am J Sports Med. 2006; 10(10):1-5.
- 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.
- Mishra AK, Woodall Jr J and Vieira A. Treatment of tendon and muscle using platelet-rich plasma. Clin Sports Med, January 2009; 28(1): 113-125.
- Mishra AK. Treatment of chronic severe elbow tendinosis with platelet rich plasma. 2005 Annual Meeting, American Academy of Orthopaedic Surgeons. Paper 2003.
- Mohamadi S, Norooznezhad AH, Mostafaei S, et al. A randomized controlled trial of effectiveness of platelet-rich plasma gel and regular dressing on wound healing time in pilonidal sinus surgery: Role of different affecting factors. Biomed J. Dec 2019; 42(6): 403- 410.
- Monto RR. Platelet-rich plasma efficacy versus corticosteroid injection treatment for chronic severe plantar fasciitis. Foot Ankle Int. Apr 2014; 35(4):313-318.
- Moraes VY, Lenza M, Tamaoki MJ et al. Platelet-rich therapies for musculoskeletal soft tissue injuries. Cochrane Database Syst Rev 2013; 12:CD010071.
- Morishita M, Ishida K, Matsumoto T, et al. Intraoperative platelet-rich plasma does not improve outcomes of total knee arthroplasty. J Arthroplasty. Dec 2014; 29(12):2337-2341.
- National coverage determination (NCD) for blood-derived products for chronic non-healing wounds (270.3). Centers for Medicare and Medicaid Services. Effective date of version August 2, 2012. https://www.cms.gov/medicare-coverage-database/details/ncd-details.aspx? NCDId=217&ncdver=5&NCAId=260&bc=ACAAAAAAQAAA&. Accessed November 13, 2019.
- National Institute for Health and Clinical Excellence. Autologous blood injection for plantar fasciitis. NICE interventional procedure guidance 437. 2013. //www.nice.org.uk/nicemedia/live/13883/62398/62398.pdf.
- National Institute for Health and Care Excellence (NICE). Autologous blood injection for tendinopathy [IPG438]. 2013; //www.nice.org.uk/guidance/ipg438.
- National Institute for Health and Clinical Excellence (NICE). Diabetic foot problems: prevention and management [NG19]. 2016; //www.nice.org.uk/guidance/ng19.
- National Institute for Health and Clinical Evidence. Interventional Procedure Guidance 279: Autologous blood injection for tendinopathy. Issue date January 2009. www.nice.org.uk/nicemedia/pdf/IPG279Guidance.PDF.
- National Institute for Health and Care Excellence (NICE). Platelet-rich plasma injections for osteoarthritis of the knee: Interventional procedure guidance [IPG491]. 2014; nice.org.uk/guidance/ipg491.
- National Institute for Health and Care Excellence (NICE). Platelet-rich plasma injections for knee osteoarthritis: Interventional procedure guidance [IPG637]. 2019;https://www.nice.org.uk/guidance/ipg637/chapter/1-Recommendations.
- Niezgoda JA, Van Gils CC, Frykberg RG and Hodde JP. Randomized clinical trial comparing OASIS Wound Matrix to Regranex Gel for diabetic ulcers. Adv Skin Wound Care, June 2005; 18(5 Pt 1): 258-266. (Abstract)
- Nin JR, Gasque GM, Azcarate AV et al. Has platelet-rich plasma any role in anterior cruciate ligament allograft healing? Arthroscopy. Nov 2009; 25(11):1206-1213.
- Oliveira BGRB, Carvalho MR, Ribeiro APL. Cost and effectiveness of Platelet Rich Plasma in the healing of varicose ulcer: Metaanalysis. Rev Bras Enferm. 2020; 73(4): e20180981.
- Patel S, Dhillon MS, Aggarwal S, et al. Treatment with platelet-rich plasma is more effective than placebo for knee osteoarthritis: a prospective, double-blind, randomized trial. Am J Sports Med. Feb 2013; 41(2):356-364.
- 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):255-262.
- Picard F, Hersant B, Bosc R, et al. The growing evidence for the use of platelet-rich plasma on diabetic chronic wounds: a review and a proposal for a new standard care. Wound Repair Regen. Sep 2015; 23(5):638-643.
- Qaseem A, Humphrey LL, Forciea MA, et al. Treatment of pressure ulcers: a clinical practice guideline from the American College of Physicians. Ann Intern Med. Mar 03 2015; 162(5):370-379.
- Qi KQ, ChenTJ PJL, Shang XL. The application of autologous platelet-rich gel in the treatment of diabetic foot ulcers. Chin J Diabetes. 2014;22: 1102-1105.
- Qu W, Wang Z, Hunt C, Morrow AS, Urtecho M, Amin M, Shah S, HasanB, Abd-Rabu R, Ashmore Z, Kubrova E, Prokop LJ, Murad MH. Platelet-Rich Plasma forWound Care in the Medicare Population. Technology Assessment Program Project ID 040-353-492.
- Rabago D, Best TM, Zgierska A et al. A systematic review of four injection therapies for lateral epicondylosis: prolotherapy, polidocanol, whole blood and platelet rich plasma. Br J Sports Med 2009 Jan 21. British Journal of Sports Medicine 2009; 43:471-481.
- 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):518-528.
- Rees RS, Robson MC, et al. Becaplermin gel in the treatment of pressure ulcers: a phase II randomized, double-blind, placebo-controlled study. Wound Repair Regen, May-June 1999; 7(3): 141-147.
- Reyes-Sosa R, Lugo-Radillo A, Cruz-Santiago L, et al. Clinical comparison of platelet-rich plasma injection and daily celecoxib administration in the treatment of early knee osteoarthritis: a randomized clinical trial. J Appl Biomed. 2020;18(2-3):41-45.
- 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):113-122.
- 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):1234-1241.
- Saad Setta H, Elshahat A, Elsherbiny K, et al. Platelet-rich plasma versus platelet-poor plasma in the management of chronic diabetic foot ulcers: a comparative study. Int Wound J. Jun 2011; 8(3): 307-12.
- Saha S, Patra AC, Gowda SP, et al. Effectiveness and safety of autologous platelet-rich plasma therapy with total contact casting versus total contact casting alone in treatment of trophic ulcer in leprosy: An observer-blind, randomized controlled trial. Indian J Dermatol Venereol Leprol. May-Jun 2020; 86(3): 262-271.
- Saldalamacchia G, Lapice E, Cuomo V, et al. A controlled study of the use of autologous platelet gel for the treatment of diabetic foot ulcers. Nutr Metab Cardiovasc Dis. Dec 2004; 14(6): 395-6.
- 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. May 2016; 32(5):906-918.
- Sampson S, Gerhardt M, Mandelbaum. Platelet rich plasma injections grafts for musculoskeletal injuries: a review. Curr Rev Musculoskelet Med 2008.
- Samuel G, Menon J, Thimmaiah S, et al. Role of isolated percutaneous autologous platelet concentrate in delayed union of long bones. Eur J Orthop Surg Traumatol. Nov 22 2017.
- 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 Jun;47(7).
- 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):926-930.
- Serra R, Grande R, Butrico L, et al. Skin grafting and topical application of platelet gel in the treatment of vascular lower extremity ulcers. Acta Phlebologica. 2014 01 Dec;15(3):129-36.
- Serraino GF, Dominijanni A, Jiritano F, et al. Platelet-rich plasma inside the sternotomy wound reduces the incidence of sternal wound infections. Int Wound J. Jun 2015; 12(3):260-264.
- 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.
- Shetty SH, Dhond A, Arora M, et al. Platelet-Rich Plasma Has Better Long-Term Results Than Corticosteroids or Placebo for Chronic Plantar Fasciitis: Randomized Control Trial. J Foot Ankle Surg. Jan 2019;58(1):42-46.
- Sidman JD, Lander TA and Finkelstein M. Platelet-rich plasma for pediatric tonsillectomy patients. Laryngoscope, October 2008; 118(10): 1765-1767.
- Singh SP, Kumar V, Pandey A, et al. Role of platelet-rich plasma in healing diabetic foot ulcers: a prospective study. J Wound Care. Sep 02 2018; 27(9): 550-556.
- Slaninka I, Fibir A, Kaska M, et al. Use of autologous platelet-rich plasma in healing skin graft donor sites. J Wound Care. Jan 02 2020; 29(1): 36-41.
- Smith PA. Autologous conditioned plasma injections provide safe and efficacious treatment for knee osteoarthritis: an FDA-sanctioned, randomized, double-blind, placebo-controlled clinical trial. Am J Sports Med. Apr 2016;44(4):884-891.
- Snow M, Hussain F, Pagkalos J et al. The effect of delayed injection of leukocyte-rich platelet-rich plasma (LR-PRP) following rotator cuff repair on patient function: A randomized double-blind controlled trial. Arthroscopy. 2019 Nov.
- Sridharan K SG. Growth factors for diabetic foot ulcers: mixed treatment comparison analysis of randomized clinical trials. Br J Clin Pharmacol. 2018 Mar;84(3):434-444. doi: 10.1111/bcp.13470. Epub 2018 Jan 5.
- Steed DL, Edington HD, Webster MW. Recurrence rate of diabetic neurotrophic foot ulcers healed using topical application of growth factors released from platelets. Wound Repair Regen. Apr-Jun 1996; 4(2): 230-3.
- Steed DL, Goslen JB, Holloway GA, et al. Randomized prospective double-blind trial in healing chronic diabetic foot ulcers. CT-102 activated platelet supernatant, topical versus placebo. Diabetes Care. Nov 1992; 15(11): 1598-604.
- Tabrizi A, Dindarian S, Mohammadi S. The Effect of Corticosteroid Local Injection Versus Platelet-Rich Plasma for the Treatment of Plantar Fasciitis in Obese Patients: A Single-Blind, Randomized Clinical Trial. J Foot Ankle Surg. Jan 2020; 59(1): 64-68.
- Trams E, Kulinski K, Kozar-Kaminska K, et al. The Clinical Use of Platelet-Rich Plasma in Knee Disorders and Surgery-A Systematic Review and Meta-Analysis. Life (Basel). Jun 25 2020; 10(6).
- Tsai CH, Hsu HC, et al. Using the growth factors-enriched platelet glue in spinal fusion and its efficiency. J Spinal Disord Tech, Jun 2009; 22(4): 246-250.
- Tsikopoulos K, Tsikopoulos I, Simeonidis E, et al. The clinical impact of platelet-rich plasma on tendinopathy compared to placebo or dry needling injections: a meta-analysis. Phys Ther Sport. Jan 2016; 17:87-94.
- Tubach F, Ravaud P, Baron G, et al. Evaluation of clinically relevant changes in patient reported outcomes in knee and hip osteoarthritis: the minimal clinically important improvement. Ann Rheum Dis. Jan 2005; 64(1):29-33.
- U.S. Food and Drug Administration (FDA). Tissue and Tissue Products. //www.fda.gov/BiologicsBloodVaccines/TissueTissueProducts/.
- U.S. Food and Drug Administration. Guidance for Industry, Chronic Cutaneous Ulcer and Burn Wounds -- Developing Products for Treatment. ed2006. //www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm071324.pdf.
- Walsh MR, Nelson BJ, Braman JP, et al. Platelet-rich plasma in fibrin matrix to augment rotator cuff repair: a prospective, single-blinded, randomized study with 2-year follow-up. J Shoulder Elbow Surg. 2018 Sep;27(9):1553-1563.
- Wang Y, Han C, Hao J et al. Efficacy of platelet-rich plasma injections for treating Achilles tendonitis : Systematic review of high-quality randomized controlled trials. Orthopade. 2019 Sep;48(9).
- 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):263-270.
- Xie J, Fang Y, Zhao Y, et al. Autologous Platelet-Rich Gel for the Treatment of Diabetic Sinus Tract Wounds: A Clinical Study. J Surg Res. Mar 2020; 247: 271-279.
- Xu Z, Luo J, Huang X, et al. Efficacy of platelet-rich plasma in pain and self-report function in knee osteoarthritis: a best-evidence synthesis. Am J Phys Med Rehabil. Nov 2017;96(11):793-800.
- Yang L, Gao L, Lv Y, et al. Autologous platelet-rich gel for lower-extremity ischemic ulcers in patients with type 2 diabetes. International Journal of Clinical and Experimental Medicine. 2017 30 Sep;10(9):13796-801.
- Yang J, Sun Y, Xu P, et al. Can patients get better clinical outcomes by using PRP in rotator cuff repair: a meta-analysis of randomized controlled trials. J Sports Med Phys Fitness. Nov 2016; 56(11):1359-1367.
- Yeung CY HP, Wei LG, Hsia LC, Dai LG, Fu KY, Dai NT. Efficacy of Lyophilised Platelet-Rich Plasma Powder on Healing Rate in Patients With Deep Second Degree Burn Injury: A Prospective Double-Blind Randomized Clinical Trial. Ann Plast Surg. 2018 Feb;80(2S Suppl 1):S66-S69.
- Zhang L Qiang D, Sun YH. Clinical observation of autologous platelet rich gel in the treatment of diabetic foot ulcers. Ningxia Med J. 2016;38:809-811.
- Zhao JG, Zhao L, JiangYX, et al. Platelet-rich plasma in arthroscopic rotator cuff repair: a meta-analysis of randomized controlled trials. Arthroscopy. Jan 2015; 31(1):125-135.
- Zhao XH, Gu HF, Xu ZR, et al. Efficacy of topical recombinant human platelet-derived growth factor for treatment of diabetic lower-extremity ulcers: Systematic review and meta-analysis. Metabolism. Oct 2014; 63(10):1304-1313.
- Zhou SF, Estrera AL, Loubser P, et al. Autologous platelet-rich plasma reduces transfusions during ascending aortic arch repair: a prospective, randomized, controlled trial. Ann Thorac Surg. Apr 2015; 99(4):1282-1290.
Medical Policy Group, May 2005 (3)
Medical Policy Group, June 2005
Medical Policy Group, July 2005 (2)
Medical Policy Administration Committee, July 2005
Available for comment August 6-September 19, 2005
Medical Policy Group, November 2006 (1)
Medical Policy Group, November 2007 (1)
Medical Policy Group, February 2009 (2)
Medical Policy Administration Committee, May 2009
Available for comment April 9-May 23, 2009
Medical Policy Group, April 2010 (1): Policy updated, Description, Key Points, Policy Update, Key Words
Medical Policy Administration Committee, May 2010
Available for comment May 7-June 17, 2010
Medical Policy Group, June 1010 (2)
Medical Policy Administration, June 2010
Available for comment June 18-August 2, 2010
Medical Policy Group, June 2011; Updated Key Points & References
Medical Policy Group, April 2012 (3): 2012 Updates-Key Points & References
Medical Policy Group, November 2012: Added Code D7921 effective 1/1/13.
Medical Policy Panel, April 2013
Medical Policy Group, April 2013 (1): Update to Title with addition of ‘recombinant’ and removal of ‘primary and miscellaneous’; Added HCPCS code G0460 with retro effective date of 08/02/2012; condensed Policy section with no change to coverage criteria; update to Key Points and References
Medical Policy Panel, May 2014
Medical Policy Group, June 2014 (1): Clarification to policy statements to further define what is not covered, no change to intent of policy or what is covered/non-covered; Update to Key Points and References
Medical Policy Panel, May 2015
Medical Policy Group, June 2015 (2): 2015 Updates to Title, Description, Key Points, Approved by Governing Bodies, Current coding: CPT code 86999 added, and References; policy statement updated to include a list of some of the conditions that are not covered for platelet-rich plasma; no change to intent.
Medical Policy Panel, January 2016
Medical Policy Group, January 2016 (2): 2016: Updates to Title, Key Points, Approved by Governing Bodies, and References; no change in policy statement.
Medical Policy Panel, April 2016:
Medical Policy Group, April 2016 (7): 2016 Updates to Key Points, References; no change in policy statement.
Medical Policy Panel, April 2017
Medical Policy Group, May 2017 (7): 2017 Updates to Description, Key Points, Approved by Governing Bodies & References. No change to policy statement.
Medical Policy Group, December 2017: Annual Coding Update 2018. Added new CPT code 0481T effective 1/1/18 to the Current Coding section.
Medical Policy Panel, April 2019
Medical Policy Group, May 2019 (7): Updates to Key Points & References. No change to policy statement.
Medical Policy Panel, January 2020
Medical Policy Group, January 2020 (5): Updates to Description, Key Points, Approved by Governing Bodies, and References. No change to Policy Statement.
Medical Policy Panel, April 2020
Medical Policy Group, April 2020 (7): Updates to Key Points and References. No change to Policy Statement.
Medical Policy Panel, April 2021
Medical Policy Group, April 2021 (7): Updates to Key Points and References. Policy section updated to remove “not medically necessary” statements. No change in intent.
This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.
This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.
The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.
As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.
The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:
- The technology must have final approval from the appropriate government regulatory bodies;
- The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;
- The technology must improve the net health outcome;
- The technology must be as beneficial as any established alternatives;
- The improvement must be attainable outside the investigational setting.
Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:
- In accordance with generally accepted standards of medical practice; and
- Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and
- Not primarily for the convenience of the patient, physician or other health care provider; and
- Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.