Definition and Overview
Autologous platelet-rich plasma (PRP) treatment is a regenerative medicine procedure that promotes tissue regeneration and healing by injecting plasma obtained by concentrating platelets from the patient's own peripheral blood to a high concentration into the damaged area. When the high concentration of platelets contained in PRP are activated, numerous growth factors are released from platelet alpha granules, and these growth factors promote tissue repair processes such as cell proliferation, angiogenesis, and collagen synthesis.
The concept of PRP was first proposed in the field of hematology in the 1970s, and clinical application began in the 1990s for the purpose of promoting healing during bone transplantation in oral and maxillofacial surgery. Marx (2004) systematically organized the growth factor mechanism and clinical evidence of PRP, the scope of application was expanded to include orthopedics, sports medicine, rehabilitation medicine, and dermatology. Recently, research is being conducted on the effect of PRP on supplying neurotrophic factors in the field of nerve regeneration.
Because autologous blood is used, the risk of blood-borne infection or immune rejection is extremely low, and it is a relatively simple procedure that can be performed in an outpatient setting within 30 to 40 minutes. However, since the composition varies depending on the manufacturing method of PRP, platelet concentration ratio, and whether white blood cells are included, the establishment of a standardized protocol is continuously being discussed.
Platelets and growth factors
Platelets are nonnucleated cell fragments with a diameter of 2 to 3 μm derived from megakaryocytes in the bone marrow. The concentration of platelets in normal blood is 150,000 to 350,000/μL, and in PRP, this is concentrated 3 to 5 times more (at least 1,000,000/μL). In addition to hemostatic functions, platelets store various bioactive substances in alpha granules, dense granules, and lysosomes, and release them when activated to regulate tissue healing.
The main growth factors released from PRP are as follows.
Platelet-derived growth factor (PDGF)
Platelet-derived growth factor (PDGF) is a representative growth factor released from platelet alpha granules. It promotes mitosis of mesenchymal stem cells and fibroblasts and induces cell migration (chemotaxis) to the damaged area. It also promotes the proliferation of smooth muscle cells in the blood vessel wall, contributing to the repair of damaged blood vessels.
Transforming growth factor-beta (TGF-β)
Transforming growth factor-beta (TGF-β) is a key factor that promotes the synthesis of extracellular matrix. It increases the production of connective tissue components such as collagen, fibronectin, and proteoglycan, and plays a central role in the healing process of tendons and ligaments.
Vascular endothelial growth factor (VEGF)
Vascular endothelial growth factor (VEGF) is a major factor that induces angiogenesis. It promotes the proliferation and migration of endothelial cells to form new capillaries at the damaged area, which improves nutrient supply and oxygen delivery and accelerates tissue regeneration.
Other growth factors
In addition, PRP includes epidermal growth factor (EGF), insulin-like growth factor (IGF-1), and fibroblast growth factor (FGF). These growth factors act not singly but in combination and sequentially to mediate the entire process of inflammation control, cell proliferation, and tissue remodeling.
PRP manufacturing method
PRP manufacturing involves three steps: blood collection, centrifugation, and plasma extraction.
blood draw
Approximately 20 to 60 mL of blood is collected from the patient's arm vein into a dedicated tube containing an anticoagulant (ACD-A or sodium citrate). The amount of blood collected is determined by the PRP kit used and the treatment area.
centrifugation
The collected blood is placed in a centrifuge and spun to separate the blood components into layers according to specific gravity. Centrifugation methods include single-spin and double-spin.
The one-time centrifugation method involves centrifuging once with a relatively low rotational force (soft spin) to separate the red blood cell layer and the plasma layer, and then extracting the platelet-rich lower plasma layer. The two-time centrifugation method separates red blood cells through first centrifugation, centrifuges the upper plasma layer again at high rotation force (hard spin), precipitates platelets into a pellet, and then resuspends them in a small amount of plasma. Two centrifugation methods achieve higher platelet concentration rates.
Plasma extraction and platelet concentration
The platelet concentration of the final extracted PRP is 3 to 5 times that of regular blood. Marx (2004) suggested 1,000,000/μL (approximately 4 to 5 times that of normal blood) as the minimum platelet concentration for therapeutic effect. However, there are reports that if the concentration ratio is too high (more than 8 times), an inhibitory effect may occur, so setting an appropriate concentration range is important.
PRP is classified into leukocyte-rich PRP (LR-PRP) and leukocyte-poor PRP (LP-PRP) depending on whether it contains leukocytes. LR-PRP, which contains white blood cells, is advantageous for antibacterial action, but may have a strong inflammatory response, while LP-PRP is advantageous for minimizing inflammatory responses when injected into a joint.
Indications
PRP treatment is applied in various fields, focusing on musculoskeletal diseases.
musculoskeletal disorders
Knee osteoarthritis is a representative indication for PRP. Intra-articular PRP injection promotes the proliferation of chondrocytes and extracellular matrix synthesis and suppresses inflammation of the synovium, leading to improved joint function and reduced pain.
In partial tears of the rotator cuff, PRP promotes healing of tendon tissue and is also applied as an adjunct during rotator cuff repair surgery. Lateral epicondylitis (tennis elbow) is a painful disease caused by degenerative changes in the tendon attachment area on the outside of the elbow, and the results of a randomized controlled trial have reported that PRP injections have better long-term effects than steroid injections.
The application of PRP is also increasing in chronic tendon diseases such as Achilles tendinopathy, plantar fasciitis, and patellar tendinopathy.
spinal disease
The effectiveness of intravertebral disc PRP injections is being studied for chronic back pain associated with intervertebral disc degeneration. Basic research has reported that growth factors can delay the progression of intervertebral disc degeneration by promoting proliferation of nucleus pulposus cells and matrix synthesis. Application of PRP injection is also being attempted in facet joint syndrome and sacroiliac joint dysfunction.
nerve regeneration
Among the growth factors included in PRP, PDGF, IGF-1, and VEGF are also involved in nerve regeneration. Research is underway on promoting nerve regeneration after peripheral nerve injury, PRP injection around the median nerve in carpal tunnel syndrome, and relieving neuropathic pain. In animal experiments, it was reported that applying PRP promoted Schwann cell proliferation and axon regeneration.
Hair loss (androgenic alopecia)
In androgenetic alopecia, injecting PRP into the scalp promotes angiogenesis around hair follicles and increases the activity of dermal papilla cells, thereby inducing hair growth. Several randomized controlled trials have reported significant increases in hair density and thickness after PRP treatment.
Procedure
PRP treatment is completed in about 30 to 40 minutes in an outpatient setting.
Preparation before procedure
Patients are advised to stop taking non-steroidal anti-inflammatory drugs (NSAIDs) for one week before the procedure. This is because NSAIDs can reduce the therapeutic effect of PRP by inhibiting platelet function. Patients taking anticoagulants should consult their doctor in advance.
Blood collection and PRP manufacturing
1. Approximately 20 to 30 mL of blood is collected from an arm vein into a special tube containing an anticoagulant. 2. The collected blood is transferred to a kit dedicated to producing PRP and then centrifuged in a centrifuge for about 10 to 15 minutes. 3. After centrifugation, blood is separated into the red blood cell layer (lower layer), the buffy coat (middle layer where platelets and white blood cells are concentrated), and the plasma layer (upper layer). 4. The platelet-enriched fraction (approximately 3 to 6 mL) is extracted into a syringe.
PRP injection
1. Disinfect the treatment area. 2. Under ultrasound guidance, the position of the needle is checked in real time and accurately enters the target area. 3. The extracted PRP is slowly injected. 4. In the case of intra-articular injection, the joint is flexed and extended several times after injection so that the PRP is evenly distributed within the joint.
Effect and evidence
knee osteoarthritis
The effectiveness of PRP for knee osteoarthritis is the area in which the most clinical evidence has been accumulated. Patel et al. (2013), in a prospective double-blind randomized controlled trial, the PRP injection group significantly improved the WOMAC (Western Ontario and McMaster Universities Arthritis Index) total score at 6 months compared to the placebo group (saline solution), and clinically significant pain reduction was reported in approximately 73% of patients.
Andia and Maffulli (2014)'s systematic literature review showed that PRP had equal or superior results compared to hyaluronic acid injection in terms of pain reduction and functional improvement at 12-month follow-up. Multiple meta-analyses have reported that PRP intra-articular injections are superior to hyaluronic acid and steroid injections in terms of long-term effects (6 to 12 months).
Tendon disease (tennis elbow, Achilles tendinopathy)
For lateral epicondylitis (tennis elbow), Sampson et al. (2008) reported that PRP injection promotes healing in tendon degeneration areas and that the short-term (4 weeks) effect is similar to that of steroid injection, but the long-term (6 to 12 months) effect is significantly superior. This is because steroids are effective in suppressing short-term inflammation but do not contribute to the structural recovery of tendon tissue, whereas PRP induces tissue regeneration through growth factors.
In Achilles tendinopathy, Filardo et al. (2015) reported that functional improvement was maintained in approximately 80% of patients as a result of follow-up for 4 years after PRP treatment. This suggests that the tissue regenerative effect of PRP is based on structural healing rather than simple symptom relief.
When effects occur and how long they last
PRP induces gradual improvement through a biological healing process rather than an immediate analgesic effect. Pain reduction begins 2 to 4 weeks after the procedure, and full effects appear over 6 to 12 weeks. In studies of knee osteoarthritis, the effects of PRP injections were reported to last for 6 to 12 months, and in some studies, significant improvements were maintained up to 24 months.
Side effects and precautions
Common Adverse Reactions
Because PRP uses autologous blood, the risk of blood-borne infection or immune response is extremely low. Common adverse reactions that may occur after the procedure are as follows.
- Pain at the injection site: Stiffness or pain may appear at the injection site for 2 to 5 days after the procedure. This is part of the initial inflammatory response caused by growth factors and disappears naturally.
- Swelling: Temporary joint swelling may occur after intra-articular injection.
- Bruising (ecchymosis): Bruising may occur at the blood collection site or injection site and disappears within 1 to 2 weeks.
rare complications
- Infection: The risk of infection is extremely low if aseptic manipulation is thoroughly performed, but the theoretical possibility exists.
- Nerve or blood vessel damage: Ultrasound-guided procedures can minimize the risk of damage to surrounding structures.
- Intra-articular calcification: Very rare cases of intra-articular calcification have been reported after repeated injections.
Contraindications
- Platelet dysfunction or thrombocytopenia
- Active infection or sepsis
- Skin infection at the treatment site
- Malignancy (at or adjacent to the treatment site)
- Taking anticoagulants (need to consult with your doctor)
- pregnancy
Precautions
You should stop taking NSAIDs such as aspirin and ibuprofen for one week before the procedure. These drugs may reduce the therapeutic effect of PRP by inhibiting the cyclooxygenase pathway in platelets. Acetaminophen (Tylenol) does not affect platelet function, so it can be used for pain relief before and after the procedure.
Post-procedure care
Immediately after the procedure, take rest for 10 to 15 minutes before returning home. Management on the day of and after the procedure is as follows.
- Avoid strenuous exercise and lifting heavy objects on the day of the procedure.
- For 48 hours after the procedure, it is recommended to use heat rather than cold compress on the treated area. This is because cold compresses can inhibit platelet activation and growth factor release.
- Avoid taking NSAIDs (ibuprofen, naproxen, etc.) for at least one week after the procedure. If you have pain, use acetaminophen.
- Avoid drinking alcohol for 48 hours after the procedure.
- Pain or swelling at the injection site may occur for 2 to 3 days after the procedure, which is a normal healing reaction.
- In the case of joint injections, avoid excessive load on the joints for 1 to 2 days after the procedure, but light joint movements help ensure even distribution of PRP.
- The progress is checked 1 to 2 weeks after the procedure, and the schedule for additional procedures is determined depending on the treatment response.
The interval between repeat treatments is determined depending on the disease and response to treatment, and is generally performed 2 to 3 times at 2 to 4 week intervals. In chronic tendon disease or advanced osteoarthritis, the procedure may be performed 3 to 4 times.