The Effect of Leukocyte Concentration on Platelet-Rich Plasma Injections for Knee Osteoarthritis

Osteoarthritis is the most common musculoskeletal progressive disease, with the knee as the most commonly affected joint in the human body. While several new medications are still under research, many symptomatic therapy options, such as analgesics (opioid and non-opioid), nonsteroid anti-inflammatory drugs, symptomatic slow-acting drugs in osteoarthritis, and preparations for topical administration, are being used, with a diverse clinical response and inconsistent conclusions across various professional societies guidelines. The concept of pharmacogenomic-guided therapy, which lies on principles of the right medication for the right patient in the right dose at the right time, can significantly increase the patient’s response to symptom relief therapy in knee osteoarthritis. Corticosteroid intra-articular injections and hyaluronic acid injections provoke numerous discussions and disagreements among different guidelines, even though they are currently used in daily clinical practice. Biological options, such as platelet-rich plasma and mesenchymal stem cell injections, have shown good results in the treatment of osteoarthritis symptoms, greatly increasing the patient’s quality of life, especially when combined with other therapeutic options. Non-inclusion of the latter therapies in the guidelines, and their inconsistent stance on numerous therapy options, requires larger and well-designed studies to examine the true effects of these therapies and update the existing guidelines.

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AB0862 CONSENSUS STATEMENT ON INTRA-ARTICULAR INJECTIONS OF PLATELET-RICH PLASMA FOR THE MANAGEMENT OF KNEE OSTEOARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.618 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1738.3-1738

Author(s):

F. Eymard ◽

P. Ornetti ◽

J. Maillet ◽

E. Noel ◽

P. Adam ◽

...

Keyword(s):

Knee Osteoarthritis ◽

Task Force ◽

Platelet Rich Plasma ◽

Symptomatic Treatment ◽

Future Research ◽

List Type ◽

Clinical Practices ◽

Efficient Treatment ◽

Symptomatic Knee Osteoarthritis ◽

Symptomatic Knee

Background:There has been much debate regarding the use of intra-articular injections of platelet-rich plasma (PRP) as symptomatic treatment for knee osteoarthritis. The heterogeneity of the preparation and injection protocols limits the extrapolation of data from randomized controlled trials and meta-analyses.Objectives:The objective of this expert consensus was to develop the first clinical practice recommendations for PRP injections in knee osteoarthritis.Methods:Fifteen physicians (10 rheumatologists, 4 specialists in rehabilitation and sport medicine and 1 interventional radiologist) from different countries were selected given to their expertise in the fields of PRP and osteoarthritis. Twenty-five recommendations were finally retained after several meetings using the modified Delphi method to establish clinical consensus. All experts voted their agreement or not for each recommendation using a score between 1 (totally inappropriate) and 9 (totally appropriate). Depending on the median value and extreme scores, recommendations were judged as appropriated or unappropriated with a strong or relative agreement but could also be judged as uncertain due to indecision or absence of consensus.Results:The main recommendations are listed below:- Intra-articular injections of PRP constitute an efficient treatment of early or moderate symptomatic knee osteoarthritis. Median = 8 [6-9] – Appropriate. Relative agreement.- Intra-articular injections of PRP may be useful in severe knee osteoarthritis (Kellgren-Lawrence grade IV). Median = 7 [6-7] – Appropriate. Relative agreement.- Intra-articular injections of PRP in knee osteoarthritis should be proposed as second-line therapy, after failure of non-pharmacological and pharmacological (oral and topic) symptomatic treatment. Median = 9 [5-9] – Appropriate. Relative agreement.- Intra-articular injections of PRP should not be performed in osteoarthritis flare-up with significant effusion. Median = 7 [5-9] – Appropriate. Relative agreement.- Intra-articular PRP treatment may include 1 to 3 consecutive injections. Median = 9 [7-9] – Appropriate. Strong agreement.- Leukocyte-poor PRP should be preferred for knee OA treatment. Median = 8 [5-9] – Appropriate. Relative agreement.- PRP injections should be performed under ultrasound or fluoroscopic guidance. Median = 8 [3-9] – Uncertain. No consensus.- PRP should not be mixed with injectable anesthetic or corticosteroid. Median = 9 [6-9] – Appropriate. Relative agreement.Conclusion:Twenty-five recommendations were discussed by an international multidisciplinary task force group in order to provide a basis for standardization of clinical practices and future research protocols.Disclosure of Interests:Florent Eymard Consultant of: Regenlab, Paul Ornetti: None declared, Jérémy Maillet Consultant of: Regenlab, Eric Noel Consultant of: Regenlab, Philippe Adam Consultant of: Regenlab, Virginie Legré Boyer Consultant of: Regenlab, Thierry Boyer Consultant of: Regenlab, Fadoua Allali: None declared, Vincent Grémeaux Bader: None declared, Jean-François Kaux: None declared, Karine Louati: None declared, Martin Lamontagne Consultant of: Pendopharm, Fabrice Michel: None declared, Pascal Richette: None declared, Hervé Bard Consultant of: Regenlab

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Treating Knee Osteoarthritis With Platelet-Rich Plasma and Hyaluronic Acid Combination Therapy: A Systematic Review

The American Journal of Sports Medicine ◽

10.1177/0363546521998010 ◽

2021 ◽

pp. 036354652199801

Author(s):

Michael R. Baria ◽

W. Kelton Vasileff ◽

James Borchers ◽

Alex DiBartola ◽

David C. Flanigan ◽

...

Keyword(s):

Systematic Review ◽

Hyaluronic Acid ◽

Combination Therapy ◽

Knee Osteoarthritis ◽

Platelet Rich Plasma ◽

Case Series ◽

Final Analysis ◽

Preparation Technique ◽

Randomized Studies ◽

Patient Reported

Background: Platelet-rich plasma (PRP) and hyaluronic acid (HA) are injectable treatments for knee osteoarthritis. The focus of previous studies has compared their efficacy against each other as monotherapy. However, a new trend of combining these 2 injections has emerged in an attempt to have a synergistic effect. Purpose: To systematically review the clinical literature examining the combined use of PRP + HA. Design: Systematic review. Methods: A systematic review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines using PubMed and Embase. The following search terms were used: knee osteoarthritis AND platelet rich plasma AND hyaluronic acid. The review was performed by 2 independent reviewers who applied the inclusion/exclusion criteria and independently extracted data, including methodologic scoring, PRP preparation technique, HA composition, and patient-reported outcomes (PROs). Results: A total of 431 articles were screened, 12 reviewed in full, and 8 included in the final analysis: 2 case series, 3 comparative, and 3 randomized studies. Average follow-up was 9 months. The modified Coleman Methodology Score was 38.13 ± 13.1 (mean ± SD). Combination therapy resulted in improved PROs in all studies. Of the comparative and randomized studies, 2 demonstrated that combination therapy was superior to HA alone. However, when PRP alone was used as the control arm (4 studies), combination therapy was not superior to PRP alone. Conclusion: Combination therapy with PRP + HA improves PROs and is superior to HA alone but is not superior to PRP alone.

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In vitro responses to platelet-rich-plasma are associated with variable clinical outcomes in patients with knee osteoarthritis

Scientific Reports ◽

10.1038/s41598-021-90174-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Habib Zahir ◽

Bijan Dehghani ◽

Xiaoning Yuan ◽

Yurii Chinenov ◽

Christine Kim ◽

...

Keyword(s):

Knee Osteoarthritis ◽

Clinical Outcomes ◽

Inflammatory Responses ◽

Platelet Rich Plasma ◽

Autologous Blood ◽

Limited Information ◽

Knee Oa ◽

Patient Reported ◽

Treatment Comparisons

AbstractAutologous blood-derived products such as platelet-rich plasma (PRP) are widely used to treat musculoskeletal conditions, including knee osteoarthritis (OA). However, the clinical outcomes after PRP administration are often variable, and there is limited information about the specific characteristics of PRP that impact bioactivity and clinical responses. In this study, we aimed to develop an integrative workflow to evaluate responses to PRP in vitro, and to assess if the in vitro responses to PRP are associated with the PRP composition and clinical outcomes in patients with knee OA. To do this, we used a coculture system of macrophages and fibroblasts paired with transcriptomic analyses to comprehensively characterize the modulation of inflammatory responses by PRP in vitro. Relying on patient-reported outcomes and achievement of minimal clinically important differences in OA patients receiving PRP injections, we identified responders and non-responders to the treatment. Comparisons of PRP from these patient groups allowed us to identify differences in the composition and in vitro activity of PRP. We believe that our integrative workflow may enable the development of targeted approaches that rely on PRP and other orthobiologics to treat musculoskeletal pathologies.

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The Effect of Platelet-Rich Plasma on the Intra-Articular Microenvironment in Knee Osteoarthritis

International Journal of Molecular Sciences ◽

10.3390/ijms22115492 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5492

Author(s):

Dawid Szwedowski ◽

Joanna Szczepanek ◽

Łukasz Paczesny ◽

Jan Zabrzyński ◽

Maciej Gagat ◽

...

Keyword(s):

Knee Osteoarthritis ◽

Operative Treatment ◽

Animal Studies ◽

Platelet Rich Plasma ◽

Treatment Options ◽

Treatment Protocols ◽

Metabolic Functions ◽

Inflammatory Drugs ◽

Positive Effect

Knee osteoarthritis (KOA) represents a clinical challenge due to poor potential for spontaneous healing of cartilage lesions. Several treatment options are available for KOA, including oral nonsteroidal anti-inflammatory drugs, physical therapy, braces, activity modification, and finally operative treatment. Intra-articular (IA) injections are usually used when the non-operative treatment is not effective, and when the surgery is not yet indicated. More and more studies suggesting that IA injections are as or even more efficient and safe than NSAIDs. Recently, research to improve intra-articular homeostasis has focused on biologic adjuncts, such as platelet-rich plasma (PRP). The catabolic and inflammatory intra-articular processes that exists in knee osteoarthritis (KOA) may be influenced by the administration of PRP and its derivatives. PRP can induce a regenerative response and lead to the improvement of metabolic functions of damaged structures. However, the positive effect on chondrogenesis and proliferation of mesenchymal stem cells (MSC) is still highly controversial. Recommendations from in vitro and animal research often lead to different clinical outcomes because it is difficult to translate non-clinical study outcomes and methodology recommendations to human clinical treatment protocols. In recent years, significant progress has been made in understanding the mechanism of PRP action. In this review, we will discuss mechanisms related to inflammation and chondrogenesis in cartilage repair and regenerative processes after PRP administration in in vitro and animal studies. Furthermore, we review clinical trials of PRP efficiency in changing the OA biomarkers in knee joint.

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Clinical Efficacy of Platelet-Rich Plasma Injection and Its Association With Growth Factors in the Treatment of Mild to Moderate Knee Osteoarthritis: A Randomized Double-Blind Controlled Clinical Trial As Compared With Hyaluronic Acid

The American Journal of Sports Medicine ◽

10.1177/0363546520986867 ◽

2021 ◽

Vol 49 (2) ◽

pp. 487-496

Author(s):

Yong-Beom Park ◽

Jun-Ho Kim ◽

Chul-Won Ha ◽

Dong-Hyun Lee

Keyword(s):

Hyaluronic Acid ◽

Growth Factors ◽

Knee Osteoarthritis ◽

Clinical Outcomes ◽

Clinical Efficacy ◽

Global Assessment ◽

Platelet Rich Plasma ◽

Patient Global Assessment ◽

Symptomatic Knee Osteoarthritis ◽

Symptomatic Knee

Background: Although platelet-rich plasma (PRP) has potential as a regenerative treatment for knee osteoarthritis, its efficacy varies. Compositional differences among types of PRP could affect clinical outcomes, but the biological characterization of PRP is lacking. Purpose: To assess the efficacy of intra-articular PRP injection in knee osteoarthritis as compared with hyaluronic acid (HA) injection and to determine whether the clinical efficacy of PRP is associated with its biological characteristics. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 110 patients with symptomatic knee osteoarthritis received a single injection of leukocyte-rich PRP (1 commercial kit) or HA. Clinical data were assessed at baseline and at 6 weeks and 3 and 6 months after injection. The primary endpoint was an improvement in the International Knee Documentation Committee (IKDC) subjective score at 6 months, and the secondary endpoints were improvements in scores based on the Patient Global Assessment, the visual analog scale (VAS) for pain, the Western Ontario and McMaster Universities Osteoarthritis Index, and the Samsung Medical Center patellofemoral score. Cell counts and concentrations of growth factors and cytokines in the injected PRP were assessed to determine their association with clinical outcomes. Results: PRP showed significantly improvement in IKDC subjective scores at 6 months (11.5 in the PRP group vs 6.3 in the HA group; P = .029). There were no significant differences between groups in other clinical outcomes. The Patient Global Assessment score at 6 months was better in the PRP group ( P = .035). The proportion of patients who scored above the minimal clinically important difference (MCID) for VAS at 6 months was significantly higher in the PRP group ( P = .044). Within the PRP group, the concentrations of platelet-derived growth factors were high in patients with a score above the MCID for VAS at 6 months. The incidence of adverse events did not differ between the groups ( P > .05). Conclusion: PRP had better clinical efficacy than HA. High concentrations of growth factors were observed in patients who scored above the MCID for clinical outcomes in the PRP group. These findings indicate that concentration of growth factors needs to be taken into consideration for future investigations of PRP in knee osteoarthritis. Registration: NCT02211521 (ClinicalTrials.gov identifier).

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