How is platelet-rich plasma (PRP) prepared?

PRP is prepared from a patient’s own blood using a controlled, multi-step laboratory process designed to concentrate platelets while preserving platelet integrity and biologic activity. The specific volume of blood drawn is determined by the anatomic location, tissue type, and intended PRP formulation, as different indications may require different platelet concentrations. This approach is consistent with published PRP consensus recommendations emphasizing that PRP is not a single uniform product and should be indication specific.(1-4)

Step 1: Blood collection
Venous blood is drawn using sterile technique into anticoagulated collection tubes to prevent premature platelet activation. Baseline hematologic parameters, including platelet count, may be assessed prior to processing, as recommended by PRP classification frameworks that emphasize platelet dose and purity. (1,2)

Step 2: First centrifugation (“soft spin”)
The collected blood undergoes an initial low-force centrifugation step. This “soft spin” separates red blood cells from plasma while maintaining platelets in suspension. The goal is to isolate the platelet-containing plasma fraction while minimizing platelet activation and cellular damage. This step is a foundational component of most validated PRP preparation protocols.(3,4)

Step 3: Plasma transfer and refinement
The platelet-containing plasma layer is carefully transferred to sterile conical tubes, avoiding red blood cell contamination and controlling leukocyte inclusion when clinically appropriate. Red blood cell and leukocyte content are recognized variables that influence PRP’s inflammatory profile and post-injection tolerance.(1-3)

Step 4: Second centrifugation (“hard spin”). The plasma fraction is then subjected to a higher-force centrifugation step. This “hard spin” concentrates platelets into a visible pellet at the bottom of the tube. Excess platelet-poor plasma is removed, and the platelet pellet is resuspended to achieve a PRP formulation tailored to the clinical indication. Two-spin methods are widely supported in the literature for achieving meaningful platelet enrichment while maintaining biologic integrity.(3,4)

Balancing platelet yield and viability
Centrifugation parameters, including speed, duration, and acceleration, are selected to balance platelet concentration with platelet viability. Excessive centrifugal forces may damage platelets and reduce their functional capacity, while insufficient forces may yield subtherapeutic platelet concentrations. Consensus statements emphasize that platelet dose, purity, and viability are critical reporting elements in PRP research and clinical use.(1,2)

Final preparation and administration
The prepared PRP is maintained under sterile conditions until administration. No cell expansion, genetic modification, or donor-derived material is involved. PRP is delivered by a physician using image guidance when appropriate, consistent with best practices for musculoskeletal injections.

References

  1. DeLong JM, Russell RP, Mazzocca AD. Platelet-rich plasma: the PAW classification system. American Journal of Sports Medicine. 2012;40(4):106–114.
  2. Magalon J, Chateau AL, Bertrand B, et al. DEPA classification: a proposal for standardising PRP use. BMJ Open Sport & Exercise Medicine. 2016;2:e000060.
  3. Dohan Ehrenfest DM, Andia I, Zumstein MA, et al. Classification of platelet concentrates (PRP, PRF) and their biologic properties.
    Trends in Biotechnology. 2014;32(1):21–32.
  4. Mautner K, Malanga GA, Smith J, et al. A call for a standard classification system for PRP research. PM&R. 2015;7(4 Suppl):S53–S59.

Does insurance cover platelet-rich plasma (PRP) therapy?

In most cases, platelet-rich plasma (PRP) therapy is not covered by commercial insurance plans, Medicare, or Medicaid, and is considered an out-of-pocket expense. Coverage policies vary by insurer and indication, but PRP is commonly classified as investigational or not medically necessary for musculoskeletal conditions.

The primary reasons for limited insurance coverage include:

Regulatory status
PRP is an autologous biologic product prepared from a patient’s own blood. While PRP devices used for blood processing may be FDA-cleared, PRP itself has not been FDA-approved as a drug or biologic for the treatment of specific musculoskeletal diseases, which influences payer coverage decisions.

Heterogeneity of PRP formulations
PRP is not a single standardized product. Variability in platelet concentration, leukocyte content, activation status, and preparation methods makes it difficult for insurers to define uniform coverage criteria. This lack of standardization is widely acknowledged in PRP consensus statements and payer policy reviews.

Evolving clinical evidence
Although a growing body of randomized trials, systematic reviews, and meta-analyses suggests that PRP may improve pain and function for selected conditions (such as knee osteoarthritis and certain tendinopathies), insurers often require longer-term, indication-specific evidence and standardized protocols before approving coverage.

Classification as a biological procedure
Many insurers categorize PRP as a biologic or regenerative intervention rather than a conventional procedural service, further limiting reimbursement under existing benefit structures.

Are there exceptions?
In rare circumstances, limited reimbursement may occur when PRP is billed under specific procedural codes or within defined employer-sponsored or workers’ compensation plans; however, this is uncommon and cannot be guaranteed. Patients are encouraged to check directly with their insurer if they wish to pursue reimbursement independently.

Financial transparency
At Boulder Biologics, PRP pricing is discussed in advance during the consultation. Patients receive clear information about anticipated costs prior to treatment, enabling them to make informed decisions.

Regulatory Disclaimer
Platelet-rich plasma is an autologous biologic product prepared from a patient’s own blood. PRP has not been approved by the U.S. Food and Drug Administration (FDA) for the treatment of specific diseases or musculoskeletal conditions. Insurance coverage determinations are made by third-party payers and are independent of clinical judgment or scientific evidence. No guarantee of insurance reimbursement is made.

Is the PRP procedure painful?

Most patients experience mild to moderate discomfort during PRP procedures, though pain perception varies depending on the anatomic location treated, the underlying condition, and individual pain sensitivity.

Several factors influence procedural discomfort:

• Injection site and tissue type
Certain structures, such as tendons, periosteum, or joint capsules, are more sensitive than superficial soft tissues. Procedures involving deeper or more confined anatomic spaces may be perceived as more uncomfortable.

• Inflammatory response
PRP is intended to stimulate a localized biologic response. As a result, some patients experience transient discomfort or pressure during injection, followed by post-procedural soreness as the local inflammatory phase evolves.

• Individual pain tolerance
Pain perception varies widely among individuals and cannot be predicted with certainty.

Pain mitigation strategies
To improve patient comfort, non-acidic, non-platelet-toxic local anesthetic agents may be used to numb the skin and deeper tissues prior to injection. Ultrasound or fluoroscopic guidance is used to ensure precise placement, thereby reducing unnecessary tissue irritation and procedural discomfort. Most patients tolerate PRP procedures without difficulty and do not require sedation. When discomfort occurs, it is typically brief and manageable.

After the procedure. It is common to experience post-injection soreness or aching for several days following PRP treatment. This response is expected and reflects the platelet concentrate's biological activity. Patients are provided with post-procedure instructions to manage discomfort and optimize recovery.

Regulatory Disclaimer. Platelet-rich plasma is an autologous biologic product prepared from a patient’s own blood. Individual experiences with discomfort vary, and no guarantees can be made regarding procedural pain or post-treatment symptoms. Clinical care is based on physician judgment and individualized patient evaluation.

Can multiple injury sites be treated during a single PRP visit?

In selected cases, multiple injury sites may be treated during a single PRP visit; however, this determination is made on an individualized, case-by-case basis and depends on several clinical and safety considerations.

Factors that influence whether multiple sites can be treated include:
Anatomic location and tissue type
Treating multiple sites within the same anatomic region may be feasible, whereas treating widely separated or anatomically complex regions may require staged procedures.

Total PRP volume and formulation requirements
Each treatment site may require a specific PRP formulation and volume. The total amount of blood that can be safely drawn and processed during a single visit is taken into account.

Patient tolerance and procedural complexity. Treating multiple sites increases procedural duration and cumulative discomfort. Patient tolerance, overall health status, and ability to safely undergo multiple injections in one session are carefully considered.

Image-guidance requirements. All injections are performed using ultrasound and/or fluoroscopic guidance when appropriate. The need for precise image-guided delivery at multiple sites may influence procedural planning.

Post-procedure recovery considerations. Treating multiple areas may affect post-procedure soreness, mobility, and rehabilitation planning. Recovery instructions may differ depending on the tissues involved.

When multiple sites are treated, each injection is performed with the same attention to sterile technique, image guidance, and individualized formulation as a single-site procedure.

Regulatory Disclaimer. Platelet-rich plasma is an autologous biologic product prepared from a patient’s own blood. The decision to treat one or more sites during a single visit is based on physician judgment, patient-specific factors, and procedural safety considerations. No guarantees are made regarding outcomes or suitability for multi-site treatment.

How much blood is drawn for a PRP procedure?

The amount of blood drawn for a PRP procedure varies by patient and clinical indication and is determined during the consultation and procedural planning process. There is no single standard volume that applies to all patients.

Several factors influence the volume of blood required:

Number of treatment sites
Treating multiple anatomic areas may require a larger total PRP volume and, therefore, a greater initial blood draw.

Type and severity of injury
Different tissues and conditions may require different PRP formulations and injection volumes. Chronic or larger injuries may necessitate greater PRP volume than focal or mild conditions.

Baseline platelet count
Individual platelet counts vary based on age, sex, health status, and other biologic factors. Patients with lower baseline platelet counts may require a larger blood draw to achieve an appropriate platelet concentration.

PRP formulation goals
Target platelet concentration, leukocyte content, and red blood cell reduction influence how much starting blood volume is needed to prepare the desired PRP formulation.

Patient-specific considerations
Overall health, body size, and tolerance for blood draw are considered to ensure patient safety and comfort.

The blood draw volumes used for PRP are generally comparable to, and often less than, those drawn for routine laboratory testing or blood donation. Blood collection is performed using sterile technique, and patients are monitored throughout the process.

Regulatory Disclaimer. Platelet-rich plasma is an autologous biologic product prepared from a patient’s own blood. Blood draw volumes and PRP preparation parameters are determined based on physician judgment, current scientific understanding, and individual patient factors. No guarantees are made regarding formulation or clinical outcomes.

How effective is PRP?

Platelet-rich plasma (PRP) can be clinically helpful for selected musculoskeletal conditions, but its effectiveness is variable and depends on multiple interacting factors. PRP is not a single standardized product, and outcomes are influenced by the diagnosis, disease severity, PRP formulation, delivery technique, rehabilitation, and individual patient biology. Contemporary consensus statements emphasize that heterogeneity in PRP composition and protocols is a major reason results differ across studies and patients.(1)

Where the evidence is strongest:
Knee osteoarthritis (KOA)
Multiple randomized controlled trials and meta-analyses demonstrate that intra-articular PRP is associated with improvements in pain and function in knee osteoarthritis, particularly in mild to moderate disease and over short- to mid-term follow-up (often up to 12 months).(2-4)

When compared with hyaluronic acid (HA), several meta-analyses report PRP to be equal or superior for pain and functional outcomes in many cohorts, although effect sizes and durability vary by PRP formulation and study design.(3-4)

Clinical interpretation: PRP is most defensible in KOA when the goal is symptom and function improvement, not cartilage regeneration, and when disease is not end-stage.

Lateral epicondylitis (tennis elbow)
Systematic reviews and meta-analyses suggest that PRP may provide better longer-term pain relief and functional improvement compared with some comparators, while early outcomes may be similar across treatments.(5,6)

Clinical interpretation: PRP can be reasonable for chronic epicondylitis after failure of conservative management, with expectations that improvement often develops gradually over weeks to months.

Rotator cuff tendinopathy and selected shoulder conditions
Meta-analyses indicate that PRP is generally safe and may provide benefit in selected rotator cuff tendinopathy populations, particularly at longer follow-up intervals. However, results vary based on comparator, injection technique, and PRP formulation.(7)

Clinical interpretation: PRP may be appropriate in specific shoulder scenarios, but it is not uniformly superior across all shoulder disorders or protocols.

Where results are less predictable:
Advanced or end-stage arthritis
In severe degenerative joint disease with marked joint space loss and structural damage, PRP may still provide symptomatic relief for some patients, but the likelihood and magnitude of benefit generally decline as disease severity increases.(2-4)

Highly heterogeneous indications and protocols
When studies combine different PRP formulations (e.g., leukocyte-rich vs leukocyte-poor), dosing strategies, injection schedules, and outcome measures, results become difficult to generalize. This lack of standardization is a central theme in PRP consensus literature.(1,8)

What a typical response looks like:
Time course
When patients respond, improvement is usually gradual, often emerging over 4–12 weeks and sometimes continuing for several months. Longer-term follow-up tends to show clearer separation between PRP and comparators in some tendinopathy studies.(5,6)

Single injection versus series
Both single-injection and multi-injection protocols are reported in the literature. Some knee OA trials showing benefit, use injection series, but there is no universally accepted “best” schedule, and consensus guidance emphasizes tailoring protocols to the indication and documenting PRP composition.(1,2)

Key factors driving variability:

  • Diagnosis specificity: PRP behaves differently in osteoarthritis versus tendinopathy or ligament injury.
  • PRP composition: Platelet dose, leukocyte content, and red blood cell contamination influence inflammatory signaling and tolerability.(1,8)
  • Delivery technique: Accurate, image-guided placement is important, particularly for peri-tendinous and intra-articular injections.
  • Rehabilitation and load management: Especially in tendinopathy, outcomes depend heavily on appropriate rehabilitation.
  • Patient biology: Age, baseline platelet count, metabolic health, smoking status, and systemic inflammation can all affect response.

How we frame effectiveness at Boulder Biologics
PRP is offered when there is a sound biologic rationale and supportive clinical evidence for a given condition. Treatment goals are framed realistically: reduction in pain, improvement in function, and improved tolerance of rehabilitation, not guaranteed structural regeneration. When appropriate and with informed consent, baseline blood counts and PRP characteristics are documented to improve transparency and help explain variability in response.

Regulatory note
PRP is an autologous biologic product prepared from a patient’s own blood. It has not been approved by the U.S. Food and Drug Administration (FDA) as a drug or biologic for the treatment of specific musculoskeletal diseases. Clinical use is based on physician judgment and current scientific evidence, and outcomes cannot be guaranteed.

References

  1. Hurley ET, et al. Experts achieve consensus on a majority of statements regarding platelet-rich plasma treatments for musculoskeletal pathologies. Arthroscopy. 2024.
  2. Filardo G, Di Matteo B, Kon E, et al. Platelet-rich plasma intra-articular injections for cartilage degeneration and osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2015;23(9):2459–2470. DOI: 10.1007/s00167-013-2740-4
  3. Belk JW, Kraeutler MJ, Houck DA, et al.Platelet-rich plasma versus hyaluronic acid for knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials.Am J Sports Med. 2021;49(1):249–260.DOI: 10.1177/0363546520909397
  4. Laudy ABM, Bakker EWP, Rekers M, Moen MH. Efficacy of platelet-rich plasma injections in osteoarthritis of the knee: a systematic review and meta-analysis. Br J Sports Med. 2015;49(10):657–672. DOI: 10.1136/bjsports-2014-094036
  5. Fitzpatrick J, Bulsara M, Zheng MH. The effectiveness of platelet-rich plasma in the treatment of tendinopathy: a meta-analysis of randomized controlled clinical trials. Am J Sports Med. 2017;45(1):226–233. DOI: 10.1177/0363546516643716
  6. Coombes BK, Bisset L, Vicenzino B. Management of lateral elbow tendinopathy: one size does not fit all. Lancet. 2015;386(9992):221–232. DOI: 10.1016/S0140-6736(14)60892-6
  7. Hamid MSA, et al. Platelet-rich plasma for rotator cuff tendinopathy: a systematic review and meta-analysis. PLoS One. 2021.
  8. DeLong JM, Russell RP, Mazzocca AD. Platelet-rich plasma: the PAW classification system. Am J Sports Med. 2012.

It’s been two months, and I don’t see results yet. Why?

A lack of noticeable improvement at 6–8 weeks after PRP treatment is not uncommon and does not necessarily indicate that the therapy has failed. PRP works through biologically mediated repair and modulation processes that unfold over time, rather than through immediate pharmacologic effects. As a result, the clinical response is typically gradual, and meaningful improvement often becomes more apparent between 12 and 16 weeks after treatment.(1-3)

Why PRP responses take time:

1. PRP initiates a biologic cascade, not an instant effect: PRP delivers a concentrated platelet fraction that releases growth factors, cytokines, and signaling molecules upon activation. These signals influence inflammation, angiogenesis, cell recruitment, and matrix remodeling. This process mirrors the body’s natural healing sequence and occurs over weeks to months, not days.(1)

2. Early phases may include inflammation without symptom relief: In the first several weeks after PRP injection, the dominant biologic phase may be inflammatory or proliferative rather than reparative. During this period, patients may experience soreness, stiffness, or no clear improvement, even though underlying biologic activity is occurring. This early phase does not reliably correlate with long-term outcome.(2)

3. Tissue type matters: Different tissues heal at different rates:
• Tendons and ligaments often require longer timeframes due to limited blood supply and slow collagen turnover. Clinical improvement in tendinopathy studies frequently emerges at 3–6 months, not earlier.(3-5)
• Degenerative joint conditions such as osteoarthritis may show symptom improvement over 8–16 weeks, with some studies reporting continued gains up to 6–12 months.(2,6)
• Muscle injuries may improve more quickly, but even here variability is common.

4. PRP is not analgesic in the short term: Unlike corticosteroids, PRP does not suppress inflammation immediately. In fact, part of its proposed mechanism involves modulating, rather than eliminating, inflammatory signaling. This is one reason PRP may not provide rapid pain relief in the first few weeks but may demonstrate more durable effects later.(1,4)

5. Rehabilitation and loading influence timing: Especially for tendinopathies, clinical improvement depends heavily on appropriate rehabilitation and load management following PRP. Studies consistently show that PRP outcomes are optimized when combined with progressive, condition-specific rehabilitation rather than rest alone.(3,5)

6. Individual biology varies: Age, baseline platelet count, metabolic health, smoking status, systemic inflammation, and injury chronicity all influence response timelines. Some patients respond earlier, others later, and some may not respond despite appropriate technique and indication.(1,2)

What the literature shows about timing
Across randomized trials and meta-analyses:
• PRP often does not outperform comparators at early time points (4–8 weeks).(3-5)
• Separation between PRP and control groups is more commonly observed at 12 weeks and beyond, particularly in chronic tendinopathies and knee osteoarthritis.(2-6)
• Many studies report continued improvement at 6 months or longer, reinforcing that PRP should be evaluated over an extended timeframe rather than judged early.(2,6)

When to reassess
If there is no meaningful improvement by 3–4 months, reassessment is appropriate. This may include:
• Reviewing diagnosis and imaging
• Evaluating rehabilitation adherence and activity modification
• Considering whether additional PRP treatments, alternative biologic formulations, or different therapies are more appropriate

Early lack of response alone does not predict ultimate failure, but PRP should always be evaluated within the broader context of a comprehensive treatment plan.

How we counsel patients at Boulder Biologics
We counsel patients to assess PRP response over 12–16 weeks, with the understanding that:
• Early improvement is not required for later benefit
• Gradual, progressive change is typical
• PRP is intended to support biologic repair, not provide immediate symptom suppression

Realistic expectations and appropriate follow-up are essential components of evidence-based PRP care.

Regulatory note
PRP is an autologous biologic product prepared from a patient’s own blood. It has not been approved by the U.S. Food and Drug Administration (FDA) for the treatment of specific musculoskeletal diseases. Individual responses vary, and no outcome can be guaranteed.

References

  1. DeLong JM, Russell RP, Mazzocca AD. Platelet-rich plasma: the PAW classification system. Am J Sports Med. 2012;40(4):106–114. doi:10.1177/0363546512442374. PMID:22738751.
  2. Costa LAV, Lenza M, Irrgang JJ, Fu FH, Ferretti M. How Does Platelet-Rich Plasma Compare Clinically to Other Therapies in the Treatment of Knee Osteoarthritis? A Systematic Review and Meta-analysis. Am J Sports Med. 2023;51(4):1074–1086. doi:10.1177/03635465211062243. Epub 2022 Mar 22. PMID:35316112.
  3. Niemiec P, Szyluk K, Jarosz A, Iwanicki T, Balcerzyk A. Effectiveness of Platelet-Rich Plasma for Lateral Epicondylitis: A Systematic Review and Meta-analysis Based on Achievement of Minimal Clinically Important Difference. Orthop J Sports Med. 2022;10(4):23259671221086920. doi:10.1177/23259671221086920. PMID:35425843. PMCID:PMC9003647.
  4. Hohmann E, Tetsworth K, Glatt V. Corticosteroid injections for the treatment of lateral epicondylitis are superior to platelet-rich plasma at 1 month but platelet-rich plasma is more effective at 6 months: an updated systematic review and meta-analysis of level 1 and 2 studies. J Shoulder Elbow Surg. 2023. doi:10.1016/j.jse.2023.05.0xx (exact DOI is listed on PubMed record). PMID:37247780.
  5. amid MSA, Sazlina SG. Platelet-rich plasma for rotator cuff tendinopathy: A systematic review and meta-analysis. PLoS One. 2021;16(5):e0251111. doi:10.1371/journal.pone.0251111. PMID:33970936.
  6. Belk JW, Kraeutler MJ, Houck DA, et al. Platelet-Rich Plasma Versus Hyaluronic Acid for Knee Osteoarthritis: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Am J Sports Med. 2021;49(1):249–260. doi:10.1177/0363546520909397. PMID:32302218.