Over the past decade, platelet rich plasma (PRP) has grown in popularity in both research and clinical practice due to its potential regenerative capabilities and therapeutic efficacy. Although there is growing evidence in support of PRP, much of the research volume has presented conflicting results. This is, in part, due to the multitude of conditions PRP has been used to treat (tendon, ligament, joint). More importantly however, this discrepancy may be due to fundamental differences in PRP preparations and cellular compositions. Although multiple attempts have been made at creating a standardized classification system for PRP in the past, none have accounted for all of the characteristics of PRP which may impact efficacy.
A recent article published in PM&R by TOBI: The Orthobiologic Institute alumni and faculty including Kenneth Mautner, Gerard Malanga, Jay Smith, Brian Shiple, Victor Ibrahim, Steven Sampson, and Jay Bowen presented the PLRA classification system in an effort to provide a framework to facilitate future research, as well as determining the efficacy of PRP in treating various conditions. The PLRA classification accounts for 4 main characteristics, Platelet count, Leukocyte presence, RBC presence, and Activation.
PRP by definition is blood or serum that contains a higher than normal concentration of platelets. Prior research studies have demonstrated that ideal platelet counts may be dependent upon target tissue (bone, cartilage, tendon). For example, mesenchymal stem cell recruitment was shown to increase exponentially with platelet concentrations up to 10x baseline, however platelet counts of 2 million/microL or more demonstrated an inhibitory effect on both tenocyte behavior and endothelial cell proliferation. Additionally, optimal platelet concentration may depend upon disease stage. Therefore, it is recommended that platelet concentration, volume injected and total number of platelets injected be documented.
The second characteristic of importance in PRP preparations is WBC concentration. Although WBCs, particularly neutrophils exhibit some pro-inflammatory effects, excessive inflammation may exacerbate pain and be detrimental to soft tissue healing. For example neutrophils contain hydrolytic enzymes, some of which have demonstrated negative effects on soft tissue in vitro, whereas the phagocytic properties of macrophages may be beneficial in chronic tendinopathy. The exact role of specific WBC subtypes in tissue healing is not yet completely understood, therefore classification of PRP by the presence or absence of WBCs, including percentage of neutrophils is recommended as well.
Red blood cells have been shown to be detrimental to cartilage, and interfere with normal platelet function. To date, no studies have been done comparing the efficacy of PRP formulations with varying RBC concentration although it is recommended that the presence or absence of RBCs be reported in future research trials.
The last criteria that should be included in the classification of PRP formulations is the presence or absence of exogenous activators and if so which substance was used. The 3 main types of activators include thrombin, calcium and collagen, and each has a variable affect on the both the speed and extent of platelet activation. Recent studies have shown that natural degranulation of platelets occurs slowly over time, however those in favor of exogenous activator use claim that they allow platelets to fully release their beneficial products. Moreover, the use of activators and its impact on efficacy may be target tissue specific as mentioned earlier with platelet concentration. Although no study to date has compared the efficacy of PRP with and without exogenous activators for a particular disease or tissue type, multiple studies on osteoarthritis have included activators such as calcium chloride whereas studies on tendinopathy most often have not. Nonetheless it is recommended that the use of exogenous activators be documented and specified in all future PRP trials.
By adopting this new PLRA classification system, the hope is that different PRP subtypes and their true efficacy in a multitude of clinical conditions can be more clearly identified and applied to patient care. This will in theory help to create a more standardized approach to research efforts and treatment specificity in the research ahead.
For the latest orthobiologics research and best practices from global field leaders, join us at TOBI 2016:
The Orthobiologic Institute (TOBI)
7th Annual PRP & Regenerative Medicine Symposium with Workshops & Cadaver Labs (TOBI 2016)
June 10-12, 2016
Wynn, Las Vegas, NV
Symposium: New Research & Protocol Updates
Workshops: Basic Science & Techniques
- Lipoaspirate & Bone Marrow Aspirate
- Beginner Basics – PRP & MSK Ultrasound-guided Injections
- Peripheral Nerve Hydrodissection
Cadaver Labs: Hands-on Experience
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