Platelet-Rich Plasma as an Orthobiologic: Clinically Relevant Considerations

Regenerative Medicine

Platelet-Rich Plasma as an Orthobiologic: Clinically Relevant Considerations

  • September 29 2023
  • Companion

Published: Veterinary Clinics of North America: Small Animal Practice, 2022

Keyword: Regenerative medicine, orthobiologic, Platelet-rich plasma (PRP), growth factors, cytokines, wounds, osteoarthritis, soft tissue injury

Author(s): B.J. Carr


Platelet-rich plasma (PRP) as an orthobiologic was reviewed regarding applications in the canine, constituents, and its use in clinical practice. 


Platelet-rich plasma is an autologous blood-derived product processed to concentrate platelets and the associated growth factors and cytokines (found within platelets’ alpha granules) that is higher than baseline. The associated growth factors and cytokines that have been correlated to tissue healing include platelet-derived growth factor (PDGF), transforming growth factor-α (TGF-α), transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF), basic fibroblastic growth factor (bFGF), epidermal growth factor (EGF), connective tissue growth factor (CTGF), insulin-like growth factor (IGF), hepatocyte growth factor (HGF), and keratinocyte growth factor (KGF).  These growth factors and cytokines have been shown to promote cell recruitment, cell migration, cell proliferation, angiogenesis, and osteogenesis. PRP has also been shown to recruit, stimulate, and provide a scaffold for stem cells.  Thus, PRP has been used to manage numerous conditions including wound healing, osteoarthritis, and soft tissue injury in humans, equines, and canines. 


Canine Applications


Wound Healing 

Multiple studies on wound healing in people and dogs have found that PRP promotes wound epithelialization, reduces scar formation, exhibits antimicrobial activity, and stimulates angiogenesis.  Thus, PRP is currently being used in the canine as a biological wound healing enhancer.  


Autogolous blood-derived products have been used to manage osteoarthritis (OA) in humans, horses, and dogs to alleviate pain, reduce inflammation, and improve function.  Multiple studies in dogs with OA using a single PRP injection or series have shown improvement in validated client survey results, subjective pain and gait scores, and objective kinetic gait findings anywhere from 30 to 180days.  Numerous studies have also been performed in dogs with cranial cruciate ligament (CCL) injury and have shown PRP improved pain, lameness, effusion, and/or inflammation within the stifle.   

Soft Tissue Injury 

Tendons and ligaments have poor self-repair capability.  Concentrated growth factors and inflammatory mediators within PRP are believed to induce a transient inflammatory event that triggers tissue regeneration by stimulating cell recruitment and proliferation. Furthermore, PRP has been shown to have a beneficial immunomodulatory effect on tenocytes to stimulate the secretion of angiogenic proteins in injured tenocytes.  However, there is still limited evidence available regarding the use of PRP in the canine for tendinopathy.  

Platelet-Rich Plasma Constituents

There are multiple commercial products and formulations of autologous blood-derived products available.  Multiple studies have investigated the compositional differences of commercially available PRP systems, but there is still no consensus on optimal component concentrations. 



Numerous studies have indicated that the ideal PRP product should increase platelets anywhere from 2 to 6 fold compared with baseline CBC, depending on the clinical application.  Platelet concentration greater than 6x baseline (or >1800 x 103 platelets/µ) may be detrimental. However, there is still no consensus on the ideal platelet concentration for specific applications. 

Red Blood Cells 

Most recent studies agree that it is best to reduce red blood cells (RBC) in PRP as they have been shown to have a deleterious inflammatory effect. 

Leukocytes (Neutrophils) 

There is still much debate regarding whether leukocytes should be included in PRP, particularly neutrophils as they increase concentrations of inflammatory mediators.  Many argue that neutrophil concentration should be decreased for intra-articular applications as an increased neutrophil concentration in PRP has been shown to cause synoviocyte death. 

However, some studies suggest that leukocytes should be included in PRP for soft tissue applications as in tendinosis there is a failure of normal tendon repair in which case concentrated growth factors and inflammatory mediators within PRP work together to reinitiate a healing response. 

Mononuclear Cells 

While the direct effect of mononuclear cells remains unclear, recent studies indicate they may be beneficial in PRP as monocytes are associated with an increase in cellular metabolism and collagen production in fibroblast. 


The concentration of growth factors in PRP has been shown to be affected by its activation method.  Some methodologies include activation by physical or chemical stimuli that then cause the release of growth factors.  However, not all commercial PRP products are activated exogenously before administration as platelets are known to activate endogenously when placed in contact with collagen fibers or other coagulation factors within the extracellular matrix in situ.  Unfortunately, there remains debate as to whether PRP should be activated and if so, which activation agent is best.  


There is great debate as to which anticoagulant is best for minimizing effects on platelet function and optimizing PRP formulation.  Commonly used anticoagulants include EDTA, ACD-A, and sodium citrate.  Most commercial PRP kits for companion animals use ACD-A as it maintains the optimal pH for platelets at 7.2 while the citrate binds to calcium preventing the coagulation cascade.    

Frozen Storage 

Multiple studies have shown that platelets are no longer viable once frozen, and some studies suggest that freezing PRP changes levels of various growth factors as well as inflammatory mediators.  However, canine freeze-thawed PRP has been shown to still contain high levels of TGF-β which may be of clinical value.  Nonetheless, there is limited information on optimal freezing procedures or storage time and studies defining use or efficacy of freeze-thawed PRP vs fresh-thawed PRP in canines have not been performed.  


Platelet-Rich Plasma in Clinical Practice 



Multiple methodologies have been developed to produce PRP with various characteristics.  Typically, 5 to 60mls of whole blood is drawn from the patient into a syringe primed with anticoagulant and then processed via differential filtration or centrifugation.  PRP filtration involves passing whole blood through a gravity filtration system that is dependent on the pore size of the filter and gravity of isolate platelets. With differential centrifugation, whole blood is placed in a centrifuge for either 1 or 2 spins.  A double spin technique is thought to concentrate platelets to a higher degree than a single spin. In a double spin technique, the first “soft” spin is used to separate the RBCs.  The second “hard” spin is used to obtain the final platelet concentrate.  

Commercial Products 

Multiple studies have investigated the compositional differences of commercially available PRP systems in both the canine and feline and the heterogeneity is obvious. Two recent studies (Franklin et al. and Carr et al.) compared different commercially available PRP systems. Both studies found differences among platelet concentration and WBC concentration in the final PRP product.   

A study regarding growth factor concentration among the commercially available systems found great variation in growth factor concentration among the PRP products. 

The use of PRP in feline patients has become more common but is more challenging as they are smaller in size and thus, larger blood samples are not feasible. Additionally, feline platelets tend to aggregate more than canine platelets, which can make PRP preparation and sample quantification difficult. Two recent studies assessed various commercial PRP systems for feline use. In Ferrari et al., two systems were evaluated and it was concluded that neither system was able to concentrate platelets as well in the feline and attributed this to significant platelet aggregation.  In Chun et al., the CRT PurePRP system was found to be able to concentrate platelets by 2.5-fold and reduce both neutrophil and RBC concentration. 


It is crucial to deliver PRP directly to the site of tissue injury for it to be most effective; therefore, appropriate intra-articular injection technique and ultrasound-guided soft tissue injection techniques are crucial for success. 

Contraindications and Adverse Events 

PRP is considered safe, and well-tolerated, however, there are contraindications which include (but not limited to) anemia, patients on anticoagulants or antiplatelet therapy, neoplasia, and septic arthritis.  Complications are uncommon but if seen, are typically within the first 24hours and improve within 72hours.  This includes mild injection associated discomfort or a sterile inflammatory response (“joint flare”).  Septic arthritis could also occur and is why adhering to aseptic technique is important.  

Post Therapy Recommendations 

Following PRP therapy, exercise restriction for 14 days is typically recommended and the patient should avoid high-impact activities.   

Patients are often prescribed medications for discomfort as needed.  Antiplatelet therapies such as nonsteroidal anti-inflammatory drugs (NSAID) have been thought to be contraindicated due to the concern that they may negatively affect platelet function and diminish the effects of PRP.  Literature is controversial and NSAID use is most often not recommended.  However, NSAIDs are sometimes included in a patient’s treatment plan if indicated.  

Rehabilitation therapy is often encouraged following PRP therapy. Low-level laser therapy is also commonly recommended following PRP as photoactivation is thought to support optimal growth factor and cytokine concentrations. 


A patient’s progress should be monitored following PRP therapy with both subjective and objective outcome measures. Typically, the first reassessment is 14 days following PRP therapy.  If no improvement is noted, another PRP injection may be performed. Human and canine studies suggest that 1 to 3 PRP injections (typically performed 7 to 30days apart) should be performed in the same therapeutic cycle as multiple injections could increase and/or prolong treatment efficacy. If a patient has shown no improvement following 3 PRP injections, it is unlikely they will benefit from additional injections in that therapeutic cycle. Patients have been documented to show improvement following PRP therapy for up to 180 to 270 days 


PRP has been used to treat wounds, osteoarthritis, and soft tissue injury in the canine and has shown to be relatively safe and well-tolerated. PRP is widely available with multiple commercial systems validated for canine use that generate different PRP products. Further study is still needed to fully elucidate both indications for PRP therapy as well as optimal component concentrations for various indications. However, it is imperative that future studies adhere to a standardized universal nomenclature to describe PRP so that the indications can be clearly identified, and evidence-based protocols can be established.