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Platelet Rich Plasma: How Does It Work, and Does It Work? What Is the Evidence?

platelet rich plasma

by Stuart M. Caplen, MD

In an effort to improve healing, injection of platelet rich plasma (PRP) is currently being utilized for many different medical conditions. In 2018 it was estimated that the global PRP market was expected to grow to between $380 million and $4.5 billion in the next ten years. The cost of a single treatment, which is not covered by most insurance, was estimated at approximately $500–$2,500, with patients often needing multiple treatments.[1] This article will discuss how PRP works and look at the current evidence as to whether it does improve healing for assorted conditions.

What Is Platelet Rich Plasma?

Platelet rich plasma is derived from blood drawn from an individual, which is then used in treating that same individual. The blood is specially processed to produce plasma, containing a large number of platelets. The theory behind PRP therapy is that an injection or deposition of concentrated platelets at sites of injury may aid tissue repair by releasing biologically active factors.[2]

Platelets contain seven growth factors required for wound healing. They also contain the proteins fibrin, fibronectin, and vitronectin that are used for cell adhesion in bone, connectivetissue, and epithelial tissue. Platelet growth factors are stored in platelet alpha granules, and are released after an injury. These growth factors are secreted through the platelet cell membrane after the initiation of the blood clotting cascade. Thegrowth factors next bind to the external surface of cells in the area where they were deposited or injected. The platelets continue to synthesize and secrete more growth factors for the approximately seven days of their life span.[3] PRP theoretically can stimulate the supraphysiological release of growth factors to jump-start healing in chronic injuries, and accelerate the acute injury repair process.[2] After the platelets die, macrophages take over wound healing regulation by secreting their own growth factors.

There are many different methods of preparing PRP. Variations in PRP include: the type of anticoagulant used, the number of platelets in the concentrate, the amount of growth factors, the numbers of leukocytes or red blood cells (RBCs), whether to add a procoagulant to activate the clotting cascade in PRP, the speed of the centrifuge, which manufacture’s device is used in the PRP process, and what additional additives the PRP contains. Some authors define PRP as consisting only of platelets, whereas others noted the PRP they used contained increased concentrations of leukocytes, fibrin, or bioactive proteins. This variation in PRP products may be responsible for some of the mixed results seen in the literature.[2,3]

There are also differencesin the ability of marketed PRP centrifugation devices to separate out the platelets without lysing them, which may affect results, as damaged platelets will not secrete growth factors, and may not assist in wound healing.[2]

The reporting of PRP preparation protocols in clinical studies has been inconsistent, and a clear consensus of the best formulation has not been agreed on, making it difficult to compare outcomes from different studies.[2] Clinical use of PRP is not an FDA approved procedure, but the FDA does allow off-label use of PRP. The FDA requires the blood be collected by a single venipuncture, centrifuged, and contain at least 250,000 platelets per microliter,[1] but general consensus is that the platelet concentration in platelet-rich plasma should be around 1 million cells per microliter.[5]

When PRP contains RBCs, a local response called eryptosis may occur, which triggers the release of the cytokine macrophage migration inhibitory factor (MMIF), which inhibits the migration of monocytes and macrophages. MMIF increases pro-inflammatory signals that inhibit migration of stem cells and fibroblast proliferation and can cause significant local cellular dysfunction. It is for this reason that removing the majority of RBCs from PRP preparations is considered an important step.[2]

Whether to include leukocytes in the PRP is controversial, and the issue is far from settled. Some authors have used leukocyte-rich PRP, also called buffy coat PRP, and others have not. It is hypothesized that PRP high in leukocyte concentration provides protection from infections, contributes to angiogenesis, and increases growth factor release.[5] Study results have been mixed. One study showed leukocyte-rich PRP led to improved outcomes in rabbits with induced tendinopathies over leukocyte-poor PRP.[6] In another rabbit study, the use of leukocyte-poor PRP produced better cartilage repair than leukocyte-rich PRP.[6A] A third study found using leukocyte-poor PRP did not change the in vitro healing effects versus leukocyte-rich PRP.[7] It is thought that leukocyte-rich PRP causes more inflammation than leukocyte-poor PRP,[8] so it might be more appropriate to use leukocyte poor PRP for joint injections, where one would not want to cause more inflammation.[9]

It isnot clear if the clotting cascade needs to be artificially activated for platelets to release their growth factors for PRP to work effectively, or whether just putting the PRP into tissues is enough to start the clotting process that allows release of thegrowth factors. To activate platelets in PRP injections, a procoagulant such as thrombin or calcium chloride needs to be added to start the clotting cascade.[10] Some authors have used activated platelet PRP, while other authors have not. There is one animal study that found nonactivated platelets promoted better healing than thrombin activated platelets.[11] A small study that used PRP for hair regrowth found that the PRP did not need to be activated to work, and nonactivated PRP promoted greater hairgrowth.[12] A third study found that just preparing the platelets for PRP activated them, and additional activation was unnecessary.[13]

While some medical conditions may possibly benefit from a quick release of growth factors that can be achieved from platelet activation, such as surgical wounds, other conditions may have worse results because the growth factors may degrade before tissue receptors become available for them to bind to.[14] A mouse studyfound that excessive levels of platelet growth factor may paradoxically inhibit osteochondral regeneration.[15]

How Is PRP Prepared?[16]

  1. Blood is drawn by venipuncture from the patient in anticoagulated tubes.ACD-A is a common anticoagulant used (yellow-top blood collection tube), but a number of other anticoagulants canbe used.

  2. The blood is first centrifuged at a relatively slow speed.

  3. The platelet rich plasma is then transferred to tubes that don’t contain an anticoagulant.

  4. The platelet rich plasma is then recentrifuged at a higher speedand a platelet pellet collects at the bottom of the tube.

  5. Most of the plasma is then removed, leaving about two to four milliliters that is gently swirled to resuspend the platelets in the plasma.

  6. The PRP is then ready for use. A pro-coagulant may be added before injection if platelet activation is desired.

PRP producing machines are also available, that simplify and automate the production process.

A) whole blood in tube with anticoagulant,

B) after first centrifugation,

C) removing platelet rich plasma,

D) plasma inserted into a tube with no anticoagulant,

E and F) platelet pellet and a small amount of RBCsafter second centrifugation,

G) some plasma removed and platelets gently swirled to reliquefy PRP,

H) PRP ready for injection[17]

Leukocyte Rich PRP Preparation

To make leukocyte-rich PRP, also known as a buffy coat PRP, the blood must first be cooled to 20 to 45 degrees Celsius, followed by a high-speed centrifugation. After some plasma is removed, a low-speed centrifugation is performed. After again removing some supernatant plasma, the mixture of leukocytes and platelets are gently mixed creating the leukocyte-rich or buffy coat PRP.

Uses of PRP

PRP is being used for multiple indications in manydifferent specialties including;orthopedics, podiatry, oral surgery, sports medicine,anddermatology. This section will explore the current knowledge for some of the possible uses of PRP for medical treatments.

Chronic Wound Healing

The U.S. Department of Health and Human Services commissioned an expert panel to review the literature on Platelet-Rich Plasma for Wound Care in the Medicare Population.

Some of their conclusions were:

  • There was moderate confidence that PRP increased complete wound closure or healing for lower extremity diabetic ulcers, but there was insufficient evidence to make conclusions about hospitalization, amputations and wound recurrence.

  • The evidence was insufficient to make conclusions about the effect of PRP on wound healing in individuals with lower extremity venous ulcers or pressure ulcers.

  • The available literature suffered from important limitations such as: inadequate description of wound care procedures, wound characteristics, PRP formulation techniques, concentration and volume, and inadequate length of follow-up.[18]

One systemic review and metanalysis of a PRP gel formulation used for cutaneous wounds found wound healing was improved, compared to wound care control treatment.[19] However, a Cochrane review of PRP for chronic wounds concluded that PRP may improve the healing of foot ulcers associated with diabetes, but this was based on low quality evidence from two small randomized controlled trials. The authors felt that it was unclear whether PRP improved healing of other chronic wounds. The quality of evidence for PRP improving wound healing in chronic wounds was described as low in the Cochrane review, and the studies were either underpowered, or had a significant risk of bias. It was recommended that better designed and adequately powered clinical trials are needed to evaluate the therapy further.[20]

Soft Tissue Injuries

In a Cochrane review of PRP for soft tissue injuries, looking at studies of rotator cuff tears, shoulder impingement syndrome surgery, elbow epicondylitis, anterior cruciate ligament reconstruction, patellar tendinopathy, Achilles tendinopathy, and acute Achilles tendon rupture surgical repair, the authors’ conclusion was that there was insufficient evidence to support the use of PRP for treating musculoskeletal soft tissue injuries. They found the methods of preparing PRP varied and lacked standardization, and suggested that for the future clarity of research in this area, PRP preparation methods needed to be standardized.[21]

Lateral Epicondylitis (Tennis Elbow)

A systematic review and metanalysis of corticosteroids versus autologous blood (blood obtained and then injected into the same individual) versus PRP injections for lateral epicondylitis found in the short-term, corticosteroids were associated with the most improvement, but in the long-term patients PRP had better outcomes than the steroid or autologous blood groups.[22] However, a Cochrane review of the literature, found no benefit for the use of autologous blood or PRP injection for treatment of lateral epicondylitis. The authors concluded that it was uncertain whether they improve treatment success and pain relief, and that they probably provided little or no clinically important benefit for pain or function.[23]

An interesting study on whether genetics plays a roll in the effectiveness of PRP found that certain genetic variants of the platelet-derived growth factor beta polypeptidegene resulted in better results in the treatment of lateral epicondylitis. People with certain variants were found to have a higher concentration of platelets in whole blood, and higher levels of some platelet growth factors in their PRP than patients with other genetic variants.[24]

Plantar Fasciitis

A metanalysis of PRP for plantar fasciitis found no significant differences between injected steroids versus PRP for short and intermediate pain relief. However, limited evidence supported the conclusionthat PRP is superior to steroid treatments for long-term pain relief. The sample sizes were small with limited high-quality studies, so it was recommended additional larger studies be performed.[25] Another review of the literature found some positive effect of PRP over placebo in two studies for plantar fasciitis, but superiority of PRP over steroid injection was not found in any well-designed study reviewed.[26]

Knee Osteoarthritis

A double-blinded placebo study found PRP was not superior to placebo for pain and function improvement in knee osteoarthritis over placebo.[27] Several studies found no difference in effect between PRP and hyaluronic acid injection for knee osteoarthritis.[28,29]

Back Pain and Disc Disease

There are a small number of animal studies and case reports of successful use of PRP for discogenic disease.[30,31] A randomized blinded study of PRP for spinal discogenic pain in 47 patients found a significant improvement in pain, function, and patient satisfaction over the control group.[32] One metanalysis found that intradiscal PRP injections are effective in relieving pain and improving disabilities caused by discogenic lower back pain. However, the pain-reducing effect of PRP was not evident at one-month post-injection and only achieved statistical significance two to six months after the injections.[33] Another systematic review and metanalysis of PRP for low back pain found that compared with a control intervention, PRP injection was found to improve pain relief and patient satisfaction significantly, with no increase in adverse events.[34] Larger randomized, controlled trials are needed to confirm these findings.

Carpal Tunnel Syndrome

A small study of 60 patients comparing PRP to night splints for carpal tunnel syndrome found statistically significant symptom improvement as well as decreased size of the medial nerve (cross-sectional area is measured by ultrasound and is a reflection of nerve swelling) in the PRP group.[35]

A systematic review and meta-analysis of nine randomized controlled trials with 434 total subjects, which compared PRP to corticosteroids, saline or splinting, found that PRP could be effective for mild to moderate carpal tunnel syndrome, and superior to traditional conservative treatments in improving painand function. At one month there was a significant reduction in the cross-sectional area of the median nerve, and at three to six months other measures of patient perceived improvement occurred. At three months in a subgroup analysis, sensory nerve conduction velocity was significantly improved in the PRP group over the corticosteroid group. The authors noted with the limited number of randomized trials in the literature on PRP for carpal tunnel syndrome, the results needed confirmation with larger trials.[36]

Androgenic Alopecia

A systemic review of subcutaneous PRP injections for male pattern hair loss (androgenic alopecia) concluded that most studies reported that subcutaneous injection of PRP is likely to reduce hair loss, increase hair diameter and density in patients with androgenic alopecia, but larger and better designed studies were needed to confirm that finding.[37]

Facial Rejuvenation

There are some small studies that have looked at facial rejuvenation, where PRP is injected into the face to reduce wrinkles and sagging. There are a few small positive studies, but confirmative studies are needed.[38]


There is some suggestive evidence thatPRP injections mayhelp reduce acne scars. PRP is also being investigated for use in keloids, traumatic and post-surgical scarring. As with almost all PRP indications, more confirmatory studies are needed to assess the true efficacy of PRP for these indications [39]


While the theory behind PRP seems sound, unfortunately the efficacy of the procedure has not been definitively proven for many of the conditions which it is currently being used. Contributing to the problem is a lack of standardization of the makeup of PRP being used, the equipment used for preparation, underpowered studies and a lack of non-biased, blinded, randomized controlled trials.[1] It may be that genetic makeup also plays a role in the varying effectiveness of PRP in clinical trials.[24]

It appears PRP may be of benefit of in some conditions such as diabetic ulcers and discogenic back pain. It may also be useful in many other conditions, but definitive proof is still lacking. Despite the many mixed or negative results of PRP in the current literature for certain indications, it has become a widely used procedure, and created a new healthcare industry. Fortunately, it has a low possibility of adverse effects.

In reviewing PRP studies on lateral epicondylitis there are both positive and negative studies, and depending on which articles were chosen, one could take either side of the argument as to whether PRP is effective. Almost all reviews of PRP usage in the medical literature suggest that better data, and larger randomized controlled trials are needed to determine which medical conditions will actually benefit from PRP therapy.


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[2] Everts P, Onishi K, Jayaram P, Lana JF, Mautner K. Platelet-Rich Plasma: New Performance Understandings and Therapeutic Considerations in 2020. Int J Mol Sci. 2020;21(20):7794. Published 2020 Oct 21. Retrieved from:

[3] Marx RE. Platelet-Rich Plasma: Evidence to Support Its Use. J Oral Maxillofac Surg 62:489-496, 2004. Retrieved from:

[4] Jones IA, Togashi RC, Thomas Vangsness C Jr. The Economics and Regulation of PRP in the Evolving Field of Orthopedic Biologics. Curr Rev Musculoskelet Med. 2018;11(4):558-565. Retrieved from:

[5] Muthuprabakaran K. et al. A cross-sectional analysis of the effects of various centrifugation speeds and inclusion of the buffy coat in platelet-rich plasma preparation. Indian Journal of Dermatology, Venereology and Leprology. 87 (6); 792-799. October 2021. Retrieved from:\

[6] Jiang G et al. Comparison of leukocyte-rich platelet-rich plasma and leukocyte-poor platelet-rich plasma on achilles tendinopathy at an early stage in a rabbit model. Am J Sports Med. 2020;48:1189-99. Retrieved from:

[6A] Xu Z et al. Comparative evaluation of leukocyte- and platelet-rich plasma and pure platelet-rich plasma for cartilage regeneration. Sci Rep 7, 43301 (2017).

[7] Giusti I et al. Leukocyte depletion does not affect the in vitro healing ability of platelet rich plasma. Exp Ther Med. 2018;15:4029-38. Retrieved from:

[8] Dragoo JL et al. Comparison of the acute inflammatory response of two commercial platelet-rich plasma systems in healthy rabbit tendons. Am J Sports Med. 2012 Jun;40(6):1274-81. Retrieved from:

[9] Kim J-H et al. Adverse Reactions and Clinical Outcomes for Leukocyte-Poor Versus Leukocyte-Rich Platelet-Rich Plasma in Knee Osteoarthritis: A Systematic Review and Meta-analysis. Orthopaedic Journal of Sports Medicine. June 2021. Retrieved from: 10.1177/23259671211011948

[10] PRP Labs Editorial Team. How to Activate Platelet Rich Plasma (PRP). PRP Labs. May 6th, 2018. Retrieved from:

[11]Scherer SS et al. Non-activated versus thrombin-activated platelets on wound healing and fibroblast-to-myofibroblast differentiation in vivo and in vitro. Plast Reconstr Surg. 2012;129:46e–54e. Retrieved from:

[12] Gentile P et al. Evaluation of Not-Activated and Activated PRP in Hair Loss Treatment: Role of Growth Factor and Cytokine Concentrations Obtained by Different Collection Systems. Int J Mol Sci. 2017;18(2):408. Published 2017 Feb 14. Retrieved from:

[13] Queiroz da Silva L et al. Platelet Activation Is Not Crucial for Platelet-Rich Plasma (PRP), When Used As Autologous Therapeutic Product, and Could be Lyophilized without Any Growth Factor Loss. Blood (2016) 128 (22). Retrieved from:

[14] Cavallo C et al. “Platelet-Rich Plasma: The Choice of Activation Method Affects the Release of Bioactive Molecules,” BioMed Research International, vol. 2016, Article ID 6591717, 7 pages, 2016. Retrieved from:

[15] Ranly DM et al. Platelet-derived growth factor inhibits demineralized bone matrix-induced intramuscular cartilage and bone formation. A study of immunocompromised mice. J Bone Joint Surg Am. 2005;87(9):2052-64. Retrieved from:

[16] Dhurat R, Sukesh M. Principles and Methods of Preparation of Platelet-Rich Plasma: A Review and Author's Perspective. J Cutan Aesthet Surg. 2014;7(4):189-197. Retrieved from:

[17] Dório, M et al. Efficacy of platelet-rich plasma and plasma for symptomatic treatment of knee osteoarthritis: a double-blinded placebo-controlled randomized clinical trial. BMC Musculoskelet Disord 22, 822 (2021). Retrieved from:

[18] Platelet-Rich Plasma for Wound Care in the Medicare Population. Agency for Healthcare Research and Quality U.S. Department of Health and Human Services. Technology Assessment Project ID: MYOE59 September 17, 2020. Retrieved from:

[19] 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.Retrieved from:

[20] Martinez‐Zapata MJ et al. Autologous platelet‐rich plasma for treating chronic wounds. Cochrane Database of Systematic Reviews. 25 May 2016. Retrieved from:

[21] Moraes VY et al. Platelet-rich therapies for musculoskeletal soft tissue injuries. Cochrane Database Syst Rev. 2013 Dec 23;(12):CD010071. Update in: Cochrane Database Syst Rev. 2014;(4):CD010071. PMID: 24363098. Retrieved from:

[22] Tang S et al. Platelet-Rich Plasma Vs Autologous Blood Vs Corticosteroid Injections in the Treatment of Lateral Epicondylitis: A Systematic Review, Pairwise and Network Meta-Analysis of Randomized Controlled Trials. PM R. 2020;12(4):397-409. Retrieved from:

[23] Karjalainen TV et al. Autologous blood and platelet-rich plasma injection therapy for lateral elbow pain. Cochrane Database of Systematic Reviews 2021, Issue 9. Art. No.: CD010951. Retrieved from:

[24] Niemiec P et al. Why PRP works only on certain patients with tennis elbow? Is PDGFB gene a key for PRP therapy effectiveness? A prospective cohort study. BMC Musculoskelet Disord. 2021;22(1):710. Published 2021 Aug 18. Retrieved from:

[25] Yang WY et al. Platelet-rich plasma as a treatment for plantar fasciitis: A meta-analysis of randomized controlled trials. Medicine (Baltimore). 2017;96(44):e8475. Retrieved from:

[26] Yu, T et al. Outcomes of platelet-rich plasma for plantar fasciopathy: a best-evidence synthesis. J Orthop Surg Res 15, 432 (2020).

[27] Dório, M et al. Efficacy of platelet-rich plasma and plasma for symptomatic treatment of knee osteoarthritis: a double-blinded placebo-controlled randomized clinical trial. BMC Musculoskelet Disord 22, 822 (2021). Retrieved from:

[28] Filardo G et al. (2012b) Platelet-rich plasma intra-articular knee injections show no superiority versus viscosupplementation: a randomized controlled trial. Am J Sports Med 43:1575–1582.

[29] Cole BJ et al. Hyaluronic Acid Versus Platelet-Rich Plasma: A Prospective, Double-Blind Randomized Controlled Trial Comparing Clinical Outcomes and Effects on Intra-articular Biology for the Treatment of Knee Osteoarthritis. Am J Sports Med. 2017 Feb;45(2):339-346.

[30] Formica M, Cavagnaro L, Formica C, Mastrogiacomo M, Basso M, Di Martino A. What is the preclinical evidence on platelet rich plasma and intervertebral disc degeneration? Eur Spine J. 2015 Nov;24(11):2377-86. Retrieved from:

[31] Mohammed S, Yu J. Platelet-rich plasma injections: an emerging therapy for chronic discogenic low back pain. J Spine Surg. 2018;4(1):115-122. Retrieved from:

[32] Yetsa A et al. Lumbar Intradiskal Platelet-Rich Plasma (PRP) Injections: A Prospective, Double-Blind, Randomized Controlled Study, PM&R, Volume 8, Issue 1, 2016, Pages 1-10. Retrieved from:

[33] Chang MC, Park D. The Effect of Intradiscal Platelet-Rich Plasma Injection for Management of Discogenic Lower Back Pain: A Meta-Analysis. J Pain Res. 2021;14:505-512

[34] Xuan Z, Yu W, Dou Y, Wang T. Efficacy of Platelet-rich Plasma for Low Back Pain: A Systematic Review and Meta-analysis. J Neurol Surg A Cent Eur Neurosurg. 2020 Nov;81(6):529-534. Retrieved from:

[35] Wu, YT. et al. Six-month efficacy of platelet-rich plasma for carpal tunnel syndrome: A prospective randomized, single-blind controlled trial. Sci Rep 7, 94 (2017).

[36] Dong C, Sun Y, Qi Y, et al. Effect of Platelet-Rich Plasma Injection on Mild or Moderate Carpal Tunnel Syndrome: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials. Biomed Res Int. 2020;2020:5089378. Published 2020 Nov 14. Retrieved from:

[37] Mao, G., Zhang, G. & Fan, W. Platelet-Rich Plasma for Treating Androgenic Alopecia: A Systematic Review. Aesth Plast Surg 43, 1326–1336 (2019).

[38] Schoenberg E et al. Platelet-rich plasma for facial rejuvenation: An early examination. Clinics in Dermatology, Volume 38, Issue 2, 2020, Pages 251-253. Retrieved from:

[39] Alser OH, Goutos I. The evidence behind the use of platelet-rich plasma (PRP) in scar management: a literature review. Scars Burn Heal. 2018;4. Published 2018 Nov 18. Retrieved from:

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