Tobias Chapter 4 - PRP And ACP Flashcards
List five growth factors and cytokines found and platelet alpha granules and associated with tissue healing, derived from PRP
PDGF, TGF-α, TGF-β, VEGF, basic fibroblastic growth factor, epidermal growth factor, connective tissue growth factor, insulin-like growth factor, hepatocyte growth factor, and keratinocyte growth factor.
What is the recommended platelet concentration in PRP? Are there any disadvantages to higher concentrations?
Proposed platelet concentrations typically range from 2- to 6-fold. Moderate (2- to 3-fold) and high (4- to 6-fold) platelet concentrations may prove advantageous for the healing of soft tissue and bone injuries. Moreover, recent studies have shown that cells respond to PRP in a dose-dependent manner. On the other hand, platelet concentration greater than 6-fold (or > 1,800 X 103 platelets/μL) may result in cellular apoptosis as well as downregulation and desensitization of growth factor receptors.
Is there a downside to the presence of RBCs and PRP? Explain.
Reducing RBCs in PRP is recommended as RBCs have been shown to have a harmful inflammatory effect. Iron within RBCs may act as a catalyst to form reactive oxygen species, damaging cartilage, and synovial tissues. Strong inflammatory mediator (IL-1 and TNF-α) concentrations positively correlate with red cell increases.
Is there a downside to the presence of leukocytes in PRP? Explain.
Neutrophils inherently release potent inflammatory media- tors such as IL-1β, TNF-α, IL-6, IL-8, and matrix metalloproteinase. Such cell signaling effects may be desirable within some applications but not others. Because LR-PRP significantly induces more synoviocyte death compared with LP-PRP and PBS, it is likely advisable to minimize neutrophils within intra-articular PRP.
What are the current thoughts regarding monocytes and lymphocytes in PRP? Are they thought of as beneficial or detrimental? Explain the proposed role of each of these cells.
Monocytes are thought to increase cellular metabolism and collagen production in fibroblasts and decrease antiangiogenic cytokines interferon-γ and IL-12.
Likewise lymphocytes exhibit collagen production potential when activated by platelets through increased production of IL-6.
What is the proposed effect of PRP on the dynamics of M1 versus M2 macrophages in the synovium?
Monocyte-derived macrophages isolated from peripheral blood have been shown to respond to PRP by shifting from M1 toward a more M2 phenotype. PRP may influence monocyte-derived macrophages within the product or macrophages at the site of application. A transition toward a more dominant M2 synovial macrophage phenotype could explain the longer duration of effect seen by intra-articular PRP in joints affected by OA.
What are the proposed benefits and most common methods of platelet activation for PRP? What is the current trend regarding platelet activation?
The activation of PRP samples affects the concentration of growth factors by inducing degranulation. Platelets release most of their contents within 1 hour of activation, but viable platelets may continue to release growth factors for up to 7 days after activation. Activation methods include thermal, thrombin solution, and calcium, and the type of activation agent and platelet product composition influences the type and quantity of growth factor release. Activation agents could also directly affect changes in tissues, regardless of their platelet effects.
Most current Platelet-rich plasma (PRP) products are usually not activated before administration because they naturally degranulate when contacting certain substances, so most commercial systems do not require activation before administration. However, more evidence is needed before making strong recommendations about platelet product activation.
What is the current recommendation regarding the use of anticoagulant? Is there a preferred anticoagulant? Why?
- Anticoagulants such as EDTA, ACD-A, and sodium citrate have been used for PRP processing.
- EDTA suppresses platelet degranulation and is not commonly recommended for PRP.
- ACD-A maintains optimal pH, prevents the coagulation cascade, preserves platelet morphology and does not affect growth factor concentration.
- Sodium citrate and ACD-A support greater proliferation of mesenchymal cells than EDTA.
- A study in rabbits found that sodium citrate yielded a higher number of platelets and leukocytes while maintaining similar growth factor concentration, but ACD-A is the most common and well-supported choice.
What are the current thoughts regarding freezing of PRP?
Platelets are no longer viable once frozen, but PRP can be cryopreserved for future use, reducing the need for repeated patient collection. Although freezing alters concentrations of growth factors and inflammatory mediators, freeze-thawed PRP still retains anabolic potential. However, there are currently no direct comparisons between fresh and frozen PRP in dogs, so conclusions about the benefits, drawbacks, or optimal procedures for freezing and thawing PRP cannot be made at this time.
List 5 systemic and 2 local contraindications for the use of PRP
Contraindications for Autologous PRP Products
A. Systemic contraindications
1. Thrombocytopenia
2. Anemia
3. Antiplatelet therapy
4. Sepsis
5. Neoplasia
B. Local contraindications
1. Septic arthritis
2. Other localized contraindications (pyoderma)
What are the proposed benefits and current research regarding the use of PRP in wounds?
PRP (platelet-rich plasma) has a wide range of positive effects, including promoting wound healing and reducing scar formation, as well as exhibiting antimicrobial activity and stimulating the growth of blood vessels.
A study conducted on dogs with decubital ulcerations showed significant benefits from using autologous platelet gel, leading to a greater reduction in wound area compared to traditional gauze treatment. Additionally, PRP has been effective in promoting healing in acute wounds. However, the effectiveness of PRP can vary based on factors such as wound chronicity, sterility, patient health status, and the method of PRP application. For example, while autologous PRP injected at the margins of surgically induced canine wounds did not accelerate healing, it did improve tissue perfusion and collagen bundle formation. These differences in findings suggest the importance of considering various factors when using PRP in wound management.
What is the current status and shortcomings of the research evaluating the use of PRP for OA?
Osteoarthritis affects over 60% of the canine population. Platelet-enriched products have been found to reduce pain and lameness associated with naturally occurring OA of various joints when administered through intra-articular injections in controlled clinical trials. PRP also targets secondary stifle OA resulting from cranial cruciate ligament (CCL) disease, with evidence supporting its use in dogs, regardless of whether surgical stabilization has been conducted. In a study by Yun et al, PRP, mesenchymal stem cells, or a combination of both were compared to controls, and PRP alone or in combination with mesenchymal stem cells showed positive effects on lameness and preservation of tissue mechanics and histology. The ideal timing of PRP application for the stage of OA is still debated, but evidence supports its use in various stages of OA. It’s worth noting that while these studies are promising, there were differences in the product compositions, small study populations, and variability in the types of OA in the dogs studied. However, both PRP and ACP may provide noticeable and measurable relief from OA in dogs for up to 3 months with a single injection, based on both studies and anecdotal evidence from clinical practice.
What is the current status of research on PRP for tendinous injuries?
Platelet-rich plasma (PRP) has been found to have a beneficial effect on soft tissue healing in animals through promoting tissue regeneration, stimulating the secretion of angiogenic proteins, and increasing neovascularization and fibrocyte proliferation. The effectiveness of PRP for tendon healing and tendinopathy may depend on the site of injury, the product used, and the stage of the disease. While PRP has shown positive effects on healing canine cranial cruciate ligament (CCL) injuries, further research is needed to fully understand its potential and limitations in treating soft tissue injuries in animals.
