Definition and Overview
Platelet-rich plasma (PRP) therapy is a regenerative medicine procedure in which plasma with a high concentration of platelets obtained from the patient's own peripheral blood is injected into damaged tissues to promote tissue regeneration and healing [1]. When the concentrated platelets in PRP are activated, numerous growth factors are released from platelet alpha granules, promoting tissue repair processes including cell proliferation, angiogenesis, and collagen synthesis.
The concept of PRP was first introduced in the field of hematology in the 1970s, and clinical application began in oral and maxillofacial surgery in the 1990s to promote healing during bone grafting. After Marx (2004) systematically reviewed the growth factor mechanisms and clinical evidence for PRP, its applications expanded to orthopedics, sports medicine, rehabilitation medicine, and dermatology [1]. More recently, research has been conducted on the neurotrophic factor delivery effects of PRP in the field of neural regeneration.
Because autologous blood is used, the risk of blood-borne infection or immune rejection is extremely low, and the procedure can be performed in an outpatient setting within 30–40 minutes [3]. However, since PRP composition varies depending on the preparation method, platelet concentration factor, and leukocyte inclusion, the establishment of standardized protocols remains an ongoing discussion.
Platelets and Growth Factors
Platelets are anucleate cell fragments measuring 2–3 micrometers in diameter, derived from megakaryocytes in the bone marrow. Normal platelet concentration in blood ranges from 150,000–350,000/microL, and PRP concentrates this to 3–5 times or more (minimum 1,000,000/microL) [1]. Beyond their hemostatic function, platelets store various bioactive substances in alpha granules, dense granules, and lysosomes, which are released upon activation to regulate tissue healing.
The major growth factors released from PRP are as follows.
Platelet-Derived Growth Factor (PDGF)
PDGF is a representative growth factor released from platelet alpha granules. It stimulates mitosis of mesenchymal stem cells and fibroblasts and induces cell migration (chemotaxis) to the injury site. It also promotes proliferation of vascular smooth muscle cells, contributing to damaged vessel repair [1].
Transforming Growth Factor-Beta (TGF-beta)
TGF-beta is a key factor that promotes extracellular matrix synthesis. It increases production of connective tissue components such as collagen, fibronectin, and proteoglycans, and plays a central role in tendon and ligament healing [1] [3].
Vascular Endothelial Growth Factor (VEGF)
VEGF is a major factor that induces angiogenesis. It promotes endothelial cell proliferation and migration to form new capillaries at the injury site, thereby improving nutrient supply and oxygen delivery to accelerate tissue regeneration [3].
Other Growth Factors
PRP also contains epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1), fibroblast growth factor (FGF), and others. These growth factors act in a complex, sequential manner rather than individually, mediating the entire process of inflammation regulation, cell proliferation, and tissue remodeling [1].
PRP Preparation Methods
PRP preparation consists of three stages: blood collection, centrifugation, and plasma extraction.
Blood Collection
Approximately 20–60 mL of blood is drawn from the patient's antecubital vein into specialized tubes containing anticoagulant (ACD-A or sodium citrate). The volume of blood drawn depends on the PRP kit used and the treatment site [3].
Centrifugation
The collected blood is placed in a centrifuge and spun to separate blood components into layers based on specific gravity. Centrifugation methods include single-spin and double-spin techniques.
The single-spin method uses a relatively low centrifugal force (soft spin) to separate the red blood cell layer from the plasma layer, then extracts the platelet-rich lower plasma. The double-spin method first separates red blood cells, then centrifuges the upper plasma again at high centrifugal force (hard spin) to sediment platelets into a pellet, which is then resuspended in a small volume of plasma. The double-spin method achieves a higher platelet concentration [1].
Plasma Extraction and Platelet Concentration
The final PRP platelet concentration is 3–5 times that of whole blood. Marx (2004) proposed a minimum platelet concentration of 1,000,000/microL (approximately 4–5 times baseline) as the threshold for therapeutic efficacy [1]. However, excessively high concentration ratios (8 times or more) may paradoxically produce inhibitory effects, making it important to establish an optimal concentration range.
PRP is classified based on leukocyte content into leukocyte-rich PRP (LR-PRP) and leukocyte-poor PRP (LP-PRP). LR-PRP with leukocytes is advantageous for antimicrobial action but may produce a stronger inflammatory response, whereas LP-PRP is preferable for intra-articular injection to minimize inflammatory reactions [5].
Indications
PRP therapy is applied across various fields, primarily for musculoskeletal conditions.
Musculoskeletal Conditions
Knee osteoarthritis is one of the most representative indications for PRP. Intra-articular PRP injection promotes chondrocyte proliferation and extracellular matrix synthesis while suppressing synovial inflammation, inducing improved joint function and pain reduction [2] [5].
In partial rotator cuff tears, PRP promotes tendon tissue healing and may be applied as an adjunct during rotator cuff repair. Lateral epicondylitis (tennis elbow), a painful condition caused by degenerative changes at the lateral elbow tendon attachment, has been shown in randomized controlled trials to respond to PRP injection with superior long-term outcomes compared to corticosteroid injection [3].
PRP application is also increasing in chronic tendon conditions such as Achilles tendinopathy, plantar fasciitis, and patellar tendinopathy [4].
Spinal Conditions
The efficacy of intradiscal PRP injection for chronic low back pain associated with intervertebral disc degeneration is under investigation. Preclinical studies have reported that growth factors may promote nucleus pulposus cell proliferation and matrix synthesis, potentially delaying the progression of disc degeneration. PRP injection has also been attempted for facet joint syndrome and sacroiliac joint dysfunction.
Neural Regeneration
Among the growth factors contained in PRP, PDGF, IGF-1, and VEGF are also involved in neural regeneration. Research is ongoing regarding PRP for promoting peripheral nerve regeneration after injury, perineural PRP injection for carpal tunnel syndrome affecting the median nerve, and neuropathic pain relief. Animal studies have reported that PRP application promotes Schwann cell proliferation and axon regeneration.
Hair Loss (Androgenetic Alopecia)
In androgenetic alopecia, PRP injection into the scalp promotes angiogenesis around hair follicles and increases dermal papilla cell activity, inducing hair growth. Several randomized controlled trials have reported significant increases in hair density and thickness following PRP treatment.
Procedure Process
The PRP procedure is completed within approximately 30–40 minutes in an outpatient setting.
Pre-procedure Preparation
Patients are instructed to discontinue nonsteroidal anti-inflammatory drugs (NSAIDs) for one week before the procedure. NSAIDs can suppress platelet function and reduce the therapeutic effect of PRP. Patients taking anticoagulants should consult their physician in advance.
Blood Collection and PRP Preparation
1. Approximately 20–30 mL of blood is drawn from the antecubital vein into specialized tubes containing anticoagulant.
2. The collected blood is transferred to a dedicated PRP preparation kit and centrifuged for approximately 10–15 minutes.
3. After centrifugation, the blood separates into a red blood cell layer (bottom), buffy coat (middle layer concentrated with platelets and leukocytes), and plasma layer (top).
4. The platelet-concentrated fraction (approximately 3–6 mL) is extracted into a syringe.
PRP Injection
1. The treatment site is sterilized.
2. Under ultrasound guidance, the needle position is confirmed in real time while precisely entering the target site.
3. The extracted PRP is slowly injected.
4. For intra-articular injection, the joint is flexed and extended several times after injection to ensure even distribution of PRP within the joint.
Efficacy and Evidence
Knee Osteoarthritis
The efficacy of PRP for knee osteoarthritis has the largest body of clinical evidence. In a prospective, double-blind, randomized controlled trial by Patel et al. (2013), the PRP injection group showed significant improvement in WOMAC (Western Ontario and McMaster Universities Arthritis Index) total scores at 6 months compared to the placebo group (saline), with clinically significant pain reduction reported in approximately 73% of patients [2].
A systematic review by Andia and Maffulli (2014) showed that PRP demonstrated equivalent or superior results compared to hyaluronic acid injection in pain reduction and functional improvement at 12-month follow-up [5]. Multiple meta-analyses have reported that intra-articular PRP injection is superior to hyaluronic acid and corticosteroid injections for long-term outcomes (6–12 months).
Tendon Conditions (Tennis Elbow, Achilles Tendinopathy)
For lateral epicondylitis (tennis elbow), Sampson et al. (2008) reported that PRP injection promoted healing of the degenerative tendon site, with similar short-term (4-week) efficacy but significantly superior long-term (6–12 month) efficacy compared to corticosteroid injection [3]. While corticosteroids are effective for short-term inflammation suppression, they do not contribute to structural recovery of the tendon tissue, whereas PRP induces tissue regeneration through growth factors.
For Achilles tendinopathy, Filardo et al. (2015) reported that functional improvement was maintained in approximately 80% of patients at 4-year follow-up after PRP treatment [4]. This suggests that the tissue regeneration effect of PRP is based on structural healing rather than mere symptom relief.
Onset and Duration of Efficacy
PRP induces gradual improvement through biological healing processes rather than immediate analgesic effects. Pain reduction begins 2–4 weeks after the procedure, with full effects developing over 6–12 weeks. In knee osteoarthritis studies, the effects of PRP injection have been reported to persist for 6–12 months [2], with some studies showing significant improvement maintained up to 24 months.
Adverse Effects and Precautions
Common Adverse Reactions
Because autologous blood is used, the risk of blood-borne infection or immune reactions is extremely low. Common adverse reactions that may occur after the procedure include the following.
- Injection site pain: Soreness or pain at the injection site may occur for 2–5 days after the procedure. This is part of the initial inflammatory response induced by growth factors and resolves spontaneously.
- Swelling: Temporary joint swelling may occur after intra-articular injection.
- Bruising (ecchymosis): Bruising may develop at the venipuncture or injection site and resolves within 1–2 weeks.
Rare Complications
- Infection: The risk of infection is extremely low with strict aseptic technique, although a theoretical possibility exists.
- Nerve or vascular injury: Ultrasound-guided procedure minimizes the risk of damage to surrounding structures.
- Intra-articular calcification: Very rarely, intra-articular calcification has been reported after repeated injections.
Contraindications
- Platelet dysfunction or thrombocytopenia
- Active infection or sepsis
- Skin infection at the procedure site
- Malignancy (at or adjacent to the treatment site)
- Concurrent anticoagulant use (physician consultation required)
- Pregnancy
Precautions
NSAIDs such as aspirin and ibuprofen must be discontinued for one week before the procedure. These medications inhibit the platelet cyclooxygenase pathway and may reduce the therapeutic effect of PRP. Acetaminophen does not affect platelet function and may be used for analgesia before and after the procedure.
Post-procedure Care
After the procedure, patients rest for 10–15 minutes before being discharged. Post-procedure care guidelines are as follows.
- Avoid vigorous exercise and heavy lifting on the day of the procedure.
- For 48 hours after the procedure, warm compresses are recommended over cold compresses at the treatment site, as cold compresses may inhibit platelet activation and growth factor release.
- Avoid NSAIDs (ibuprofen, naproxen, etc.) for at least one week after the procedure. Use acetaminophen for pain relief.
- Abstain from alcohol for 48 hours after the procedure.
- Pain or swelling at the injection site may occur for 2–3 days after the procedure, which represents a normal healing response.
- For joint injections, avoid excessive load on the joint for 1–2 days after the procedure, although gentle range-of-motion exercises help distribute PRP evenly.
- Progress is assessed at 1–2 weeks after the procedure, and additional treatment sessions are scheduled based on treatment response.
The interval between repeat procedures is determined by the condition and treatment response, typically performed 2–3 times at 2–4 week intervals. For chronic tendon disease or advanced osteoarthritis, up to 3–4 sessions may be performed [2] [5].