What is the role of Platelet-rich plasma (PRP) with Alpha-2 Macroglobulin (A2M)?

From the Guidelines

Platelet-rich plasma (PRP) with Alpha-2-Macroglobulin (A2M) may be considered for patients with symptomatic osteoarthritis of the knee, as it may reduce pain and improve function, although the strength of recommendation is limited 1. When considering PRP with A2M, it's essential to weigh the potential benefits against the potential harm, and patient preference should play a substantial role in the decision-making process.

• The treatment involves drawing the patient's blood, processing it to concentrate platelets and A2M, and then injecting this preparation into the affected area.
• The standard protocol typically includes 1-3 injections spaced 2-4 weeks apart, with each session requiring 30-60 ml of blood to produce 3-6 ml of the final PRP-A2M preparation.
• Patients may experience mild soreness for 24-48 hours post-injection, during which time they should avoid anti-inflammatory medications like ibuprofen as these can interfere with the therapeutic inflammatory cascade.
• Light activity is recommended immediately after treatment, with gradual return to normal activities over 1-2 weeks.
• Results typically begin to appear within 2-4 weeks, with maximum benefits often seen around 3-6 months post-treatment. The use of PRP with A2M offers a natural alternative to corticosteroid injections, with potentially longer-lasting benefits and fewer side effects, as suggested by the limited evidence available 1.
• However, practitioners should exercise clinical judgment and be alert for emerging evidence that clarifies or helps to determine the balance between benefits and potential harm.
• The treatment works through multiple mechanisms: platelets release growth factors that promote tissue healing and regeneration, while A2M specifically inhibits destructive enzymes (matrix metalloproteinases) that break down cartilage and other tissues.

From the Research

Platelet Rich Plasma with A2M

• Platelet-rich plasma (PRP) is a volume of plasma with a platelet concentration higher than the average in peripheral blood, and it has been used to treat osteoarthritis (OA) due to its ability to promote tissue healing and anti-inflammatory effects 2.
• Alpha-2-macroglobulin (A2M) is a large plasma protein found in PRP that inhibits cartilage-degrading enzymes and could be an efficacious OA treatment independently 3.
• A2M has been shown to be an active inhibitor of joint degeneration, cartilage preservation, and improvement in quality of life for patients with knee osteoarthritis compared with a multitude of other modalities 4.

Treatment Outcomes

• Studies have reported that PRP therapy can improve musculoskeletal conditions including osteoarthritis, but the results are paradoxical, with some concluding it has no effect 2.
• A retrospective analysis of 252 patients treated with PRP for big joints OA found clinically significant improvements in pain and function, with multiple PRP shoots and high sports activity being favorable prognosis factors 5.
• A double-blinded, randomized, controlled clinical trial found that A2M-rich PRP concentrate showed comparable efficacy to PRP and corticosteroids in the treatment of mild-to-moderate knee OA, with modest improvement in knee pain and function at 6-week follow-up 3.

Mechanisms of Action

• PRP contains platelet-related growth factors that promote tissue healing and anti-inflammatory effects 6.
• A2M inhibits cartilage-degrading enzymes, which could contribute to its efficacy in treating OA 3.
• The exact mechanisms of action of PRP and A2M in treating OA are not fully understood and require further research 2, 6.