By Brennen McKenzie, MA, MSc, VMD, cVMA

Using platelet concentrates in veterinary medicine has expanded dramatically in the last 20 years. While initially used primarily to treat thrombocytopenia, platelet-rich plasma (PRP) is now popular for a wide variety of conditions, such as osteoarthritis, fractures, and chronic soft-tissue wounds. Various commercial kits are marketed to veterinarians, allowing them to concentrate platelets and other blood components in the clinic. Manufacturers of these products claim theirs is "an all-natural, drug-free pain relief option for dogs and cats"¹ and "a natural alternative to NSAIDs,"¹ which can offer "new hope" and "the realistic goal of a quick and effective recovery at an affordable price."² As is all too often the case in veterinary medicine, the evidence behind such dramatic marketing claims is weaker than such language would suggest.

High-quality clinical trials required

In addition to their role in hemostasis, platelets contain a variety of compounds involved in many other physiologic functions.^3,4 There are growth factors, which may have a role in stimulating tissue healing and regeneration. Platelets also contain both pro-inflammatory and anti-inflammatory cytokines, and they can influence the activity of mesenchymal stem cells. Further, there is abundant in vitro research showing the variety and complexity of platelet functions and suggesting they could have clinical benefits in wound healing and chronic inflammatory processes, such as osteoarthritis.

However, such in vitro research can only suggest possible clinical applications. The process of moving from theoretical uses to treatment of real patients requires validation of basic principles in animal model studies and, ultimately, high-quality clinical trials showing meaningful benefits and acceptable risks. There have been several reviews of animal model studies investigating PRP for bone and soft-tissue healing and other applications.^3-5 While much of this laboratory model evidence is supportive of beneficial effects, these reviews always note there are both negative and positive studies and the quality of much of the evidence is low. It is also difficult to draw confident conclusions from this research because of the heterogeneity in PRP products and in the treatment methods tested. This is also a problem in the clinical trial literature investigating PRP.

The actual clinical research on PRP in veterinary species is sparse and not robust. The best evidence pertains to treatment of horses; reviews of this literature conclude that while there are positive results, there are also significant limitations to the reliability of the available evidence:

• "Although the majority of equine clinical studies yielded positive results, the human clinical trials' results failed to corroborate these findings. In both species, beneficial results were more frequently observed in studies with a high risk of bias. The use of PRP in musculoskeletal lesions, although safe and promising, has still not shown strong evidence in clinical scenarios."²
• "Several factors related to PRP preparation, application, and intraindividual variability lead to inconsistent clinical results… It is important to take into consideration that many of the referred studies were not randomized and/or blinded controlled trials, and therefore should be regarded with caution… the clinical efficiency of this product in the treatment of osteoarthritis remains to be determined."⁶

The evidence in small animal species is even more limited. A handful of clinical studies in dogs have been published investigating a variety of indications and including both lab animal and natural disease models:

• Prostatic cysts—This was an uncontrolled study. Ten dogs had their cysts injected with PRP, and eventually they all resolved, but there was no comparison with other treatment or no treatment at all, so the significance of this in uncertain.⁷
• Corneal ulcers—This was a randomized, controlled trial adding PRP to conventional therapy for uncomplicated corneal ulcers. No difference was seen in healing between the groups.⁸
• Supraspinatus tendinopathy—This was an uncontrolled study of 10 dogs. Some subjects improved and others did not, but the absence of a control group and the subjective outcome measures used preclude any conclusions about efficacy.⁹
• Wound healing—This was a small study using three dogs. Eight small (6-mm) wounds were created on each dog—some were treated with PRP, while others were not. The authors reported faster healing in the PRP-treated wounds, but there was no blinding and the assessment of the wounds was subjective, so the risk of bias is high.¹⁰
• Skin flaps—This was a laboratory study in beagles. Skin flaps were created on both sides of several dogs, with one wound treated with PRP and the other not treated. Some measures of wound healing differed between the treatments and others did not, though the difference in survival of the flaps was pretty large. Assessment was not blinded, which raises the risk of bias.¹¹
• Bone healing—This was another lab study using beagles. Bone screws were placed and some were treated with PRP while others were not. No difference in bone healing was seen.¹²
• Bone healing—In this study, dogs had a defect surgically created in their radius and then fixed in place, and healing was compared between dogs treated with PRP or untreated. There was a difference in bone healing between the groups, and again some controls for bias were missing, reducing the strength of the evidence.
• Bone healing—This was a blinded, controlled study of healing in naturally occurring fractures. All subjects achieved complete healing, but there was a difference of about one week in time to radiographic resolution and fixator removal. Most other outcome measures did not differ between groups.¹³

Overall, the research in dogs is promising, but very limited. Unsurprisingly, there is even less research on PRP in cats, and no conclusions at all can be drawn about the effectiveness of this treatment in this species.

What's the evidence in humans?

As usual, when the veterinary research is limited, we turn to studies in humans to see whether a therapy is likely to be helpful. While the quantity and quality of human research is inevitably higher than that in dogs and cats, the results cannot reliably be assumed to apply to other species, so such studies can only suggest, not prove, the potential benefits of PRP in veterinary patients.

The human clinical trial research is vast, with almost 300 systematic reviews currently listed on Pubmed. The conclusions of these reviews are varied, with some claiming proven benefits while others do not support any firm conclusion. Nearly all reviews of the human clinical trial literature emphasize the evidence is limited in quality, with significant risk of residual bias; the heterogeneity of treatment methods precludes confident conclusions about efficacy despite the large number of published studies. For example, a recent review concludes, "The growing development and use of PRP preparations in wound healing and tissue repair in people will require the development of new randomized controlled studies with large sample sizes to establish therapeutic efficacy."³

Finally, we must always consider the safety as well as the potential benefits of any therapy we employ. Most studies of PRP in humans and animals find limited adverse effects. Infections and pain at the injection site are reported, though these are rare. There is little research evaluating the potential for long-term side effects, so the risk of these is unknown. The costs of PRP are also relatively low, though whether these are justified by the benefits is unclear.

Bottom line

PRP is a plausible therapy, and there is reason to believe it could be helpful for veterinary patients with arthritis, connective tissue and muscle injuries, wounds, and other conditions. However, the clinical trial in humans is encouraging though not consistently positive, and there is very little clinical research in veterinary species. Much of the veterinary research consists of small studies with significant methodological limitations, which means we cannot confidently conclude what conditions, if any, might benefit from treatment with PRP.

As with many veterinary therapies that are insufficiently tested, PRP involves a variety of commercial products that vary in ways which might be significant for their effectiveness, but which haven't been specifically tested in most, if any, of the conditions for which they are marketed.

Few significant signs of harm have been seen in the preliminary PRP research, so risks are likely small, though our confidence in this conclusion must also be limited by the absence of strong research evidence.

Brennen McKenzie, MA, MSc, VMD, cVMA, discovered evidence-based veterinary medicine after attending the University of Pennsylvania School of Veterinary Medicine and working as a small animal general practice veterinarian. He has served as president of the Evidence-Based Veterinary Medicine Association and reaches out to the public through his SkeptVet blog, the Science-Based Medicine blog, and more. He is certified in medical acupuncture for veterinarians. Columnists' opinions do not necessarily reflect those of Veterinary Practice News.

References

1. PRP for Veterinarians | MediVet Biologics. http://medivetbiologics.com/home/vets/bio-solutions/regen-med/vet-prp/. Published 2020. Accessed April 17, 2020.
2. PRP for Equine | Canine Platelet Rich Plasma Therapy. https://prpkits.com/veterinary/. Accessed April 17, 2020.
3. Cortese L, Christopherson PW, Pelagalli A. Platelet Function and Therapeutic Applications in Dogs: Current Status and Future Prospects. Animals. 2020;10(2). doi:10.3390/ani10020201
4. Tambella A, Martin S, Cantalamessa A, Serri E, Attili A. Platelet-rich Plasma and Other Hemocomponents in Veterinary Regenerative Medicine. Wounds. 2018;30(11). https://pubmed.ncbi.nlm.nih.gov/30418162/. Accessed April 17, 2020.
5. Marcazzan S, Taschieri S, Weinstein RL, Del Fabbro M. Efficacy of platelet concentrates in bone healing: A systematic review on animal studies - Part B: Large-size animal models. Platelets. 2018;29(4):338-346. doi:10.1080/09537104.2017.1384537
6. Garbin LC, Olver CS. Platelet-Rich Products and Their Application to Osteoarthritis. J Equine Vet Sci. 2020;86:102820. doi:10.1016/J.JEVS.2019.102820
7. Bigliardi E, Cantoni AM, De Cesaris V, et al. Use of platelet-rich plasma for the treatment of prostatic cysts in dogs. Can J Vet Res. 2018;82(4):264-270. http://www.ncbi.nlm.nih.gov/pubmed/30363366. Accessed April 17, 2020.
8. Edelmann M, Mohammed H, Wakshlag J, Ledbetter E. Clinical Trial of Adjunctive Autologous Platelet-Rich Plasma Treatment Following Diamond-Burr Debridement for Spontaneous Chronic Corneal Epithelial Defects in Dogs. J Am Vet Med Assoc. 2018;253(8). doi:10.2460/JAVMA.253.8.1012
9. Ho LK, Baltzer WI, Nemanic S, Stieger-Vanegas SM. Single ultrasound-guided platelet-rich plasma injection for treatment of supraspinatus tendinopathy in dogs. Can Vet J = La Rev Vet Can. 2015;56(8):845-849. http://www.ncbi.nlm.nih.gov/pubmed/26246631. Accessed April 17, 2020.
10. Jee C-H, Eom N-Y, Jang H-M, et al. Effect of autologous platelet-rich plasma application on cutaneous wound healing in dogs. J Vet Sci. 2016;17(1):79-87. doi:10.4142/jvs.2016.17.1.79
11. M K, LG P, P L, et al. Locally Injected Autologous Platelet-Rich Plasma Enhanced Tissue Perfusion and Improved Survival of Long Subdermal Plexus Skin Flaps in Dogs. Vet Comp Orthop Traumatol. 2014;27(5). doi:10.3415/VCOT-14-02-0030
12. Streckbein P, Kleis W, Buch R, Hansen T, Weibrich G. Bone Healing With or Without Platelet-Rich Plasma Around Four Different Dental Implant Surfaces in Beagle Dogs. Clin Implant Dent Relat Res. 2014;16(4). doi:10.1111/CID.12026
13. López S, Vilar JM, Sopena JJ, et al. Assessment of the Efficacy of Platelet-Rich Plasma in the Treatment of Traumatic Canine Fractures. Int J Mol Sci. 2019;20(5):1075. doi:10.3390/ijms20051075