Blog: The Plasma Edition 


Plasma - Rich, Poor, Concentrated.  This month's newsletter looks at some of the less commonly used components of blood. Two of the three spotlight articles look at PPP and acute injuries - The main blog post focuses its attention on Concentrating Plasma: A worthwhile endeavor or a fool's errand? 


Concentrated Plasma: 

One thing  PLYMOUTH MEDICAL has insisted upon when it comes to promoting products or devices used in the production of Orthobiologic treatments, is EVIDENCE. This is why we have never sold exosomes and perinatal products and why we introduced cell counting and encourage the use of very high dose PRP in line with and in support of better clinical evidence.


This is true, but, possibly with one exception: Concentrated Plasma. PLYMOUTH MEDICAL have been proponents of plasma concentration for many years. But why? The in-vitro data shows promise, but in-vivo clinical studies are few and far between and do not look good for concentrated plasma.


And it is not just PLYMOUTH MEDICAL that have been promoting this equipment:  We have seen a lot of companies selling plasma concentration filters. This recent study from Showel et al describes a protocol for producing A2M-rich plasma from platelet-poor plasma using the same filter PLYMOUTH MEDICAL have been selling for a number of years.  And we see other manufacturers - each claiming their filter is more efficient than the last, doing the same.

Understanding that plasma is approximately 92% water, the concept of filtering it to remove some of this water appears to make sense.  Filtering increases the relative concentrations of a number of key large plasma proteins, including Alpha-2-Macroglobulin, fibrinogen and Albumin. 

Some of these proteins have shown great potential benefit: On paper, A2M appears to be the front runner in terms of clinical benefit.  


A2M can bind to and neutralize certain enzymes that break down cartilage. A2M may also help reduce harmful inflammatory responses in joints. Animal studies prove that A2M can postpone cartilage degeneration by inhibiting the majority of catabolic enzymes and cytokines, making it a potentially valuable osteoarthritis treatment. One of the other concentrated proteins in plasma is albumin which serves as a very versatile and biocompatible scaffolding material.

BUT…. In concentrating the beneficial large plasma proteins, we are also concentrating all of the other large plasma proteins:  Fibrinogen for example. Fibrinogen has been shown in studies to exacerbate inflammatory joint disease through a mechanism linked to the integrin αMβ2 binding motif.

When a study is called “Plasma proteins take their toll on the joint in osteoarthritis”, perhaps we should be a bit more careful as to which proteins we are exposing the joints to. 

Here is a comparative table summarizing the A2M concentration and efficiency of various plasma concentrating devices, along with details on their performance:


Comparative Analysis of A2M Concentrating Devices

Note: Normal blood levels of A2M typically range from 1,000 to 3,000 µg/mL (or 1.5-1.8 mg/mL or ~2 mg/mL).

So where does that leave us?


Insufficient Clinical Evidence

The most glaring issue facing A2M therapy is the lack of robust clinical data. There are limited data on clinical efficacy and current studies show only modest improvements. Research demonstrates that Alpha-2-macroglobulin treatment resulted in modest improvement in knee pain and function at 6-week follow-up. Even more concerning, Alpha-2-Macroglobulin was not significantly better than (low-dose) regular PRP for knee arthritis symptoms, raising questions about whether the additional workflow complexity and cost are justified.

Most current evidence comes from animal studies rather than human trials. Results of animal experiments prove that the A2M can postpone cartilage degeneration, but translating these findings to human patients requires extensive clinical validation that simply doesn't exist yet.


Technical and Logistical Challenges & A Lack of Standardization

Extracting and concentrating A2M requires expensive equipment and a certain level of expertise, making it less accessible than PRP. Furthermore, the lack of point of care A2M testing, dosing and standardization makes it nearly impossible to compare results across studies or ensure consistent patient outcomes. This variability undermines confidence in the therapy and makes it difficult to establish evidence-based treatment protocols.


Cost-Benefit Concerns

Given that A2M shows only comparable efficacy to established treatments like PRP and corticosteroids, the additional cost and complexity may not be justified. The equipment and training requirements significantly increase treatment expenses without documented proportional improvements in patient outcomes.

Plasma does seem to have some knee pain relieving benefits, in the short term as outlined in NYU’s study. Dr. Ryan Kruse, Dr. Robbie Bowers and Dr. Scott Rodeo have each demonstrated that unconcentrated Platelet Poor Plasma (PPP) is more effective than PRP as a treatment for acute muscle injury. On paper, the constituents of plasma such as IGF could be incredibly helpful in the treatment of joint disease, but, in its concentrated form, the jury is still out. 

While we wait for the data to catch up & efficacy and dosing to be clearly demonstrated within the rigors of science, we will put our weight behind high dose Platelet Rich Plasma for the treatment of Osteoarthritis and soft tissue injury and Platelet Poor Plasma for the treatment of acute muscle injuries and continue to stick by our mission to provide our clients and their patients with products that pass the standard of peer review and clinical evidence.



Citations

  1. Berrigan W, Tao F, Kopcow J, et al. The Effect of Platelet Dose on Outcomes after Platelet Rich Plasma Injections for Musculoskeletal Conditions: A Systematic Review and Meta-Analysis. Curr Rev Musculoskelet Med. 2024;17(12):570-588. doi:10.1007/s12178-024-09922-x 

  2. Thompson, K., Shankar, D. S., Huang, S., Kirsch, T., Campbell, K. A., Gonzalez-Lomas, G., Alaia, M. J., Strauss, E. J., & Jazrawi, L. M. (2024). The Effectiveness of Alpha-2-Macroglobulin Injections for Osteoarthritis of the Knee. Bulletin of the Hospital for Joint Disease (2013), 82(4), 245–256.

  3. Showel KK, Evans CH, De la Vega RE, Hawse GP, et al. Preparation of alpha-2 macroglobulin rich plasma (A2MRP) from human blood: Technique and compositional analysis of plasma, platelet-rich plasma, platelet-poor plasma, and A2MRP. Journal of Cartilage & Joint Preservation. 2025 Jul ; (no volume or issue indicated) p. 100255. doi:10.1016/j.jcjp.2025.100255.

  4. Stephens NA. Comparison of Emcyte CORE Ultrafiltration System – Plasma Concentrator and Apex Biologix XCELL Protein Concentrator. Biofyl Scientific Research, Fort Myers, FL. Prepared for Emcyte Corporation (Patrick Pennie, CEO); April 2023. Unpublished white paper.

  5. Barry S. Coller; Blood at 70: its roots in the history of hematology and its birth. Blood 2015; 126 (24): 2548–2560. doi: https://doi.org/10.1182/blood-2015-09-659581 

  6. Vandooren J, Itoh Y. Alpha-2-Macroglobulin in Inflammation, Immunity and Infections. Front Immunol. 2021;12:803244. Published 2021 Dec 14. doi:10.3389/fimmu.2021.803244 

  7. Kuten Pella O, Hornyák I, Horváthy D, Fodor E, Nehrer S, Lacza Z. Albumin as a Biomaterial and Therapeutic Agent in Regenerative Medicine. International Journal of Molecular Sciences. 2022; 23(18):10557. https://doi.org/10.3390/ijms231810557 

  8. Flick MJ, LaJeunesse CM, Talmage KE, et al. Fibrin(ogen) exacerbates inflammatory joint disease through a mechanism linked to the integrin alphaMbeta2 binding motif. J Clin Invest. 2007;117(11):3224-3235. doi:10.1172/JCI30134 

  9. Goldring, S.R., Scanzello, C.R. Plasma proteins take their toll on the joint in osteoarthritis . Arthritis Res Ther 14, 111 (2012). https://doi.org/10.1186/ar3741

  10. Thompson K, Shankar DS, Huang S, et al. The Effectiveness of Alpha-2-Macroglobulin Injections for Osteoarthritis of the Knee. Bull Hosp Jt Dis (2013). 2024;82(4):245-256. 

08/08/2025