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 Table of Contents  
REVIEW ARTICLE
Year : 2019  |  Volume : 33  |  Issue : 3  |  Page : 126-130

Platelet-Rich Plasma for Degenerative Knee Joints: What is the Evidence?


1 Aadhya Pain Management Centre, Jaipur, Rajasthan, India
2 Daradia Pain Hospital, Kolkata, West Bengal, India
3 Department of Anaesthesiology, Adichunchanagiri Institute of Medical Sciences, Mysore, Karnataka, India
4 Department of Anaesthesiology, Rukmani Birla Hospital CK Birla, Jaipur, Rajasthan, India

Date of Submission13-Aug-2019
Date of Decision21-Sep-2019
Date of Acceptance07-Nov-2019
Date of Web Publication5-Dec-2019

Correspondence Address:
Dr. B Sarvesh
Belaku Number 90, Vivekananda Block, Teacher's Layout, Mysore - 570 029, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijpn.ijpn_57_19

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  Abstract 

Platelet-rich plasma (PRP) has been gaining popularity for degenerative joints because of its success and ease of performing procedure; however, there is a lack of standardized protocols for PRP preparation and clinical applications. Various studies have reported inconsistency and variations in their results. Evidence are inconclusive for its usage in knee osteoarthritis. We conducted a search in the English language literature using keywords such as “Platelet-rich plasma,” “knee joint,” “osteoarthritis,” “techniques,” “growth factors,” or “complications” in PubMed, Embase, and Google Scholar databases. Obtained articles were scrutinized and relevant content was included. This article has reviewed various studies regarding the definition, preparation, concentrates, and clinical application of PRP with respect to degenerative knee joint.

Keywords: Degenerative knee joint, osteoarthritis, platelet-rich plasma


How to cite this article:
Sharma K, Das G, Sarvesh B, Agarwal A. Platelet-Rich Plasma for Degenerative Knee Joints: What is the Evidence?. Indian J Pain 2019;33:126-30

How to cite this URL:
Sharma K, Das G, Sarvesh B, Agarwal A. Platelet-Rich Plasma for Degenerative Knee Joints: What is the Evidence?. Indian J Pain [serial online] 2019 [cited 2020 Jan 18];33:126-30. Available from: http://www.indianjpain.org/text.asp?2019/33/3/126/272383


  Introduction Top


Platelet-rich plasma (PRP) is defined as the volume of the plasma fraction of the autologous blood that has a platelet concentration above baseline. On the basis of the scientific evidence of PRP on bone and soft-tissue healing enhancement, the working definition of PRP has been proposed to be 10 lakh/ml in 5 ml of plasma.[1],[2] However, the concentration of platelets in PRP varies from studies to studies ranging from 2.5 to 8 times above the baseline platelet concentration.[3] Mark[1] have concluded that the effective minimum rise from the baseline concentration of the whole blood has to be 4–5 times. On the contrary effective concentrations of 2.67, 3.2, and 7.4 times were obtained by Anitua et al.,[4] Landesberg et al.,[5] and Araki et al.,[6] respectively. The zest is that ideal concentration of platelets is not yet defined properly and the present PRP definition does not hold true. There is no consensus yet regarding the concentration. It ranges from 2.67 to 7.4 times in the available literature.

There are mainly two varieties of PRP preparations, first leukocyte-rich PRP preparations, in which white blood cell (WBC) counts are above baseline, and leukocyte-poor PRP preparations, where WBC counts are below the baseline.

In recent times, utilization of PRP has increased, as it is regarded as well tolerated, with minimal complications. Preparation and injection of PRP are easy and comparatively less aggressive than other treatment modalities.


  Platelet Count Top


The individual platelet count is not constant, and it varies considerably on different days ranging from 150,000 to 350,000 platelets/μL.[7] According to the working definition of PRP, an individual with a low platelet count on the day of treatment would see a 6.5 times baseline increase in the platelet concentration. On the other hand, an individual with a high count of platelet concentration would see a three times increase from the baseline concentration. This leads to variation in quantifying a fold increase in the plasma concentration of platelets from baseline. Therefore, even though we have chosen similar protocols for different individual, the PRP products behave differently in two individuals and so is the treatment.

On the day of the procedure, it is important to document not only the absolute number of platelets/μL in the respective preparation of PRP but also the individual's own platelet count.[8]


  Platelet-Rich Plasma Methods and Systems Top


There are two basic methods of preparation of PRP[8], and the difference in their centrifugation process methods has been shown in [Table 1].
Table 1: Difference between plasma-based and buffy coat-based platelet-rich plasma system

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Not only the method of preparation differs widely but also the volume of the whole blood collected, relative centrifugal force and the centrifugation time as depicted in [Table 2].
Table 2: Different protocols for platelet-rich plasma preparation

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There is a difference in the option about the spins also. Some authors[4],[14] have cited single spin to be better while others[9],[10],[11],[12],[13] have found double spin to be better. As cited above, numerous protocols have been there in the literature describing the optimal conditions for centrifugation to get the best platelet yield. However, there is no general consensus as to which method is superior and should be recommended for the preparation of PRP.


  Platelet Activation Method Top


There are two methods of platelet activation endogenous and exogenous. Both the methods differ widely in their mechanism as listed in [Table 3].
Table 3: Difference between exogenous and endogenous system of platelet activation

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There are no recommendations regarding the activation method for platelets. Some authors[15],[16],[17],[18],[19],[20] have used the exogenous method of activations, while others[21],[22],[23],[24],[25],[26] have applied platelets directly and have concluded better results with this method.

Exogenous activators are thrombin and calcium chloride. Some researchers have used thrombin,[27] while others have believed in using calcium chloride[28],[29] still others have used a combination of both.[18],[30] Thus, in the absence of guidelines, it becomes an individual choice to use the exogenous activator of his choice.


  Individual Concentrates of Platelet-Rich Plasma Top


White blood cells

The plasma method of preparation of PRP intentionally excludes WBC; however, the buffy coat system focuses on maintaining the high concentration of WBC as stated in the article above. However, literature suggests that leukocytes have antimicrobial supportive properties in the PRP.[31] On the contrary, studies have shown that higher concentration of WBC have detrimental effect and neutrophils being the main reason.[32],[33],[34],[35],[36],[37],[38],[39],[40],[41] The growth factor platelet-derived growth factor (PDGF)-AB present in the PRP may be supplied by WBC in addition to platelets, which can affect the growth factor balance supplied by PRP preparation. Thus, the counting of the residual WBC becomes important.[42] What is the exact role of WBC remains unclear, and further studies are needed to find out the exact relevance of WBC in the PRP preparation.[43]


  Growth Factors Top


Studies have shown an increase in the concentration of growth factors such as PDGF, transforming growth factor (TGF)-β1, basic fibroblast growth factor, vascular endothelial growth factor, and epidermal growth factor as compared with their concentrations in the blood.[44],[45],[46] The functions of the above growth factors are listed in [Table 4].[47],[48],[49]
Table 4: Functions of growth factors

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Studies have shown significant variations and inconsistencies between the growth factor content and platelet counts in PRP. Not only the different PRP separation systems have yielded different growth factors content, but same PRP separation system testing different blood samples from the same individual has also shown different growth factors content.[7],[47],[50],[51]


  Platelet-Rich Plasma Injection Techniques, Postinjection Instructions, and Contraindications Top


PRP can be administered through various approaches, such as lateral,[52] superolateral,[53] parapatellar,[54] and lateral mid-patellar.[55] There is no consensus for postinjection instructions. There are several variations such as, patient is advised to rest (10 or 20 min of immobilization[55]); asked to do movement (flex and extend the knee for 5 min;[56] and knee is passively flexed and extended for ten times, followed by immobilization for 10 min in the supine position.[57] PRP injection is contraindicated in patients with coagulopathies, hemodynamic instability, local infection, and sepsis, platelet dysfunction and critical thrombocytopenia. However, steroid injection within one month at treatment site, systemic steroids within 2weeks, NSAIDS consistent use within 48hours, Hb<10g/dl, Platelet Count <105/l, Hypofibrinogenaemia, Chronic Liver pathology, and cancer of the hematopoetic are relative contraindications.[58]


  Mechanism of Action of Platelet-Rich Plasma Top


There are various theories explaining the mechanism of PRP. Once the platelets are activated either exogenously or endogenously, α granules degranulate and lead to the secretion of growth factors as listed above. These growth factors help in chemotaxis, angiogenesis, cell differentiation, and proliferation resulting in wound healing and regeneration.[59] Other than the release of the growth factors mentioned in [Table 4], platelet also releases interleukin-1 receptor antagonist which inhibits the activation n NFkB gene involved in inflammatory and apoptosis pathways. Mediators such as soluble receptors of TNF-R1 bind to its component TNF-α and prevent its cellular response. Insulin-like growth factors along with PDGF and TGF-β1 maintain a balance between the synthesis and degradation of proteoglycans and increase the chondrocyte proliferation. The growth factors also increase the synthesis of hyaluronic acid by stimulating the synovial fibroblast.[60],[61],[62],[63],[64]

Studies have shown that cell membrane of the adult mesenchymal cells, fibroblast, osteoblast, epidermal, and endothelial cells express receptors to growth factors. Once growth factors attaches to these transmembrane receptors; an endogenous internal signal protein pathway is activated, resulting in the expression of the gene involved in proliferation of cell, extracellular matrix synthesis, osteoid production, synthesis of collagen, etc.[65]


  Clinical Application of Platelet-Rich Plasma Top


Number and volume of injection

The total number of injections, PRP volume per injection, and time period between two injections are also not well defined as listed in [Table 5]. Various authors have used various protocols, and they have proved better results with the dosage they have used.
Table 5: Comparison of various protocols of platelet-rich plasma application

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Stage of the disease

Various authors have reported different effects regarding the stage of the diseases. Some[68] have found it to be effective for mild signs of degeneration, while others[53] have reported it to be effective for moderate signs of degeneration. However, some[69],[70] have reported it to be effective for both the stages of osteoarthritis (OA). Hence, there is no general consensus as which stage to use and which stage we should not.


  Effectiveness of Platelet-Rich Plasma Top


PRP does not provide immediate relief in pain. It usually takes 3–4 weeks, and thereafter, pain continues to improve over a period of 3 to 6 months following a PRP injection. There is a wide variation in the recovery time period also. Some authors have reported it to be 3 months,[57] while others have reported it to be 6 months[53],[67] and 12 months.[55],[56] However, majority publications have shown that it is beneficial in OA knee.


  Radiological Evidence Top


Studies have shown that PRP helps in the regeneration of the cartilage. However, postinjection follow-up studies using magnetic resonance imaging have shown that in approximately 73% of the cases have studied showed no change per compartment.[71]


  National Institute for Health and Care Excellence Top


Recommendations state that quality-wise evidence on the efficacy of PRP is inadequate.[72] This procedure should be used only with special arrangements for clinical governance, consent, audit, and research.


  Safety Concern Top


PRP increases the amount of growth factors which may have cancer-promoting effects. The exogenous activator bovine thrombin which was being used for the activation of platelets have resulted in life-threatening coagulopathies.[73]


  Conclusion Top


There are lots of publications, including some good-quality randomized controlled trials in support of PRP in knee joint, but there is a lack of standardization in the protocols used for the PRP preparation and the clinical application. PRP is very popular nowadays and used widely in OA knee by pain physicians, orthopedic surgeons, and physiatrists, but we need to standardize the protocol for better outcomes.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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  In this article
Abstract
Introduction
Platelet Count
Platelet-Rich Pl...
Platelet Activat...
Individual Conce...
Growth Factors
Platelet-Rich Pl...
Mechanism of Act...
Clinical Applica...
Effectiveness of...
Radiological Evi...
National Institu...
Safety Concern
Conclusion
References
Article Tables

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