Platelet-Rich Plasma Therapy and Autologous Blood
Kimberly G. Harmon
Jonathan A. Drezner
INTRODUCTION
Soft tissue injuries including tendon, muscle, and ligament injuries account for a large proportion of injuries to recreational and elite athletes. Enhancing the healing of these injuries beyond ice, rest, activity modification, and the tincture of time has been the goal of sports medicine physicians.
It is now known that nonsteroidal anti-inflammatory drugs (NSAIDs), commonly prescribed for soft tissue injury, do not enhance healing, but alleviate pain. The advent of autologous growth factor therapies holds the potential to use the body’s own healing ability to speed up and improve tissue repair. A number of different options have been investigated.
This chapter will explore the pathophysiology of autologous blood and platelet-rich plasma, examine the human literature to date, and offer conclusions based on the best available data.
AUTOLOGOUS GROWTH FACTOR THERAPIES
Concept
Growth factors mediate the biologic process of repair; individual growth factors have been shown to enhance injury repair in animal models.
By increasing the amount of growth factors to the injury, healing may be accelerated or enhanced in terms of outcome (repaired tissue more closely approximates original tissue).
Platelets are one of the first cells to arrive at injury and are filled with growth factors; growth factors in platelets are in a physiologic balance.
Contain multiple growth factors in α-granules:
□ Platelet-derived growth factor (PDGF)
□ Transforming growth factor-β (TGF-β)
□ Insulin-like growth factor (IGF)
□ Epidermal growth factor (EGF)
□ Vascular endothelial growth factor (VEGF)
□ Fibroblast growth factor (FGF)
Also contain other factors that modulate healing:
□ Serotonin
□ Adenosine diphosphate (ADP)
□ Stromal cell-derived factor-1α (SDF-1α)
Recruits circulating stem cells to site of injury
Stimulates bone marrow to release additional stem cells
Variables to Consider
The use of ultrasound (US) guidance:
24%-71% failure rate with palpation-guided injections to subacromial bursa, glenohumeral, knee, and ankle joints (12,13,21,22)
Amount of injectate: typically 2-5 cc is used depending on location and type of tissue being treated. There is a volume effect from the injection of any fluid as well as an effect from the substance itself.
Amount of and location of local anesthetic used:
Anesthetics may also be toxic to tenocytes (44).
No in vivo studies.
Procedures with tenotomy are painful without anesthetic.
Negative effect of intratendinous anesthetic should be considered.
Whether or not a fenestration is performed:
Fenestration is the repetitive passing of a needle in a tissue.
Called tenotomy when done in a tendon.
Immobilization and/or rehabilitation after the injury.
AUTOLOGOUS BLOOD
History
Percutaneous release of extensor tendons of elbow shown to be effective treatment of lateral epicondylitis (1).
Theorized by Edwards and Calandruccio (10) that the benefits of this treatment were secondary to beneficial effect of bleeding in the area, which started an inflammatory reaction that led to a cascade of healing.
Definition
Injection of a small amount (2-3 cc) of the patient’s own blood back into a damaged or injured area.
Studies
Edwards and Calandruccio, 2003 (10):
Design was case series.
Twenty-eight patients with mean age of 46 with lateral epicondylitis for at least 3 months.
Injected 2 mL of autologous blood plus 1 mL bupivacaine blindly.
Thirty-two percent got second injection at 6 weeks if pain not completely relieved.
Visual analog pain scale (VAS) decreased from 7.8 to 2.3 mm.
Seventy-nine percent of patients had complete relief of pain.
One patient (4%) failed treatment.
Connell et al., 2006 (6):
Design was case series.
Thirty-five patients with lateral epicondylitis with a mean duration of symptoms of 13.8 months; average age was 40.9.
Injected 2 mL of autologous blood under US guidance after dry needling for 1 minute.
Seventy-five percent had second injection at 4 weeks.
VAS decreased from 9 to 6 at 4 weeks and to 0 at 6 months.
Two patients (6%) failed treatment.
Suresh et al., 2006 (47):
Design was case series.
Twenty patients (average age, 48.5) with medial epicondylitis with a mean duration of symptoms for 12 months.
Injected 2 mL of autologous blood under US guidance after dry needling.
Second injection done at 4 weeks (100%).
VAS decreased from 8 to 5.65 in 4 weeks and to 2.15 at 10 months.
Three patients (15%) failed.
James et al., 2007 (27):
Design was case series.
Forty-seven patients (average age, 34.5) with patellar tendinosis for a mean duration of 12.9 months.
Injected 3 mL of autologous blood under US guidance after dry needling for 1 minute.
Second injection done at 4 weeks per protocol.
Victorian Institute of Sport Assessment Scale – Patellar (VISA-P) is a validated outcome measure for pain and functional activity in individuals with patellar tendinosis ranging from 0-100, with 100 being normal. VISA-P increased from 39.8 to 74.3.
Three treatment failures (6%).
Conclusion
Level III evidence (case series) that autologous blood injection is an effective treatment for tendinosis.
Techniques, protocols, and rehabilitation varied between studies.
PLATELET-RICH PLASMA
Terminology
Platelet rich in growth factors (PRGF)
Another term for platelet-rich plasma (PRP)
Platelet-rich fibrin matrix
Typically used to refer to PRP that has been clotted
The clot provides substance and is usually used in surgical techniques.
Platelet concentrate
A solid composition of platelets without plasma
Will not clot without plasma (no fibrin)
Platelet releasate
The product created from activated platelets, i.e., the released growth factors from the platelets
Typically created by creating a pellet of platelets in plasma and then adding thrombin to activate platelets
Fibrin glue
First described in 1970s
Polymerized fibrin induced by thrombin and calcium
Used as a tissue adhesive and to achieve hemostasis
Autologous conditioned serum
Whole blood (without anticoagulant) is incubated with glass beads for 24 hours.
Blood clots and glass beads serve as slow activators of platelets with release of growth factors.
Serum is removed.
Has increased growth factors compared to serum not incubated with glass beads (FGF and TGF-β)
Should not be confused with Autologous Conditioned Plasma, a proprietary product
Variables to Consider in PRP Product
Platelet concentration
There may be an optimum concentration of platelets above which the concentration may be inhibitory.
Graziani et al., 2006 (18) demonstrated that 2.5× baseline was optimal concentration in vitro
Han et al. (19) demonstrated that PRP with 50 ng · mL−1 TGF-β was more stimulatory then 200 ng · mL−1.
Other studies have shown that proliferation is dependent on platelet concentration, with higher concentrations being more effective (33)
Marx (34) suggested that the minimum effective amount of platelets was a concentration of 1,000,000/µL in 6 mL of PRP. Many modern platelet concentrating systems do not achieve this concentration.
Presence or absence of leukocytes
There is debate regarding whether white blood cells (WBCs) enhance or are a detriment to healing.
There are three subtypes of WBCs.
□ Neutrophils
Contain hydrolytic enzymes
Release proteases and free radicals
□ Monocytes
Primary role is removal of debris.
Balance anti-inflammatory and proinflammatory aspects of healing (11)
□ Lymphocytes
Initiate cell-to-cell interactions
Play an important role in vessel formation by supporting the proliferation and differentiation of stem cells
Viability of platelets
Once platelets are activated (by thrombin, calcium chloride, or collagen), they release 95% of their growth factors in the first hour (34Related posts:
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