Platelet Rich Plasma

(PRP) Therapy
PRP injection was first
proposed by Sanchez
etal. to improve
symptoms and
accelerate healing in
nontraumatic avulsion
fractures of the
articular cartilage in
soccer players

Osteoarthritis and Cartilage

Volume 21, Issue 11, November 2013, Pages 16271637

Basic science and clinical application of platelet-rich plasma

forcartilage defects and osteoarthritis: a review

Y. Zhu,
M. Yuan,
H.Y. Meng,
A.Y. Wang,
Q.Y. Guo,
Y. Wang,
J. Peng , ,

Cartilage defects (CDs) and the most common joint disease,

osteoarthritis (OA), are characterized by degeneration of the

articular cartilage that ultimately leads to joint destruction.
Current treatment strategies are inadequate: none results in
restoration of fully functional hyaline cartilage, for uncertain
long-term prognosis. Tissue engineering of cartilage with autocartilage cells or appropriate mesenchymal stem cell (MSC)derived cartilage cells is currently being investigated to search
for new therapies. Platelet-rich plasma (PRP), an autologous
source of factors obtained by centrifugation, possesses various
functions. For culture of MSCs and cartilage cells, it might be
substituted for fetal bovine serum (FBS) with high efficiency and
safety. It enhances the regeneration of cartilage cells when
added to cartilage tissue engineering constructs for repairing
CDs and as regenerative injection therapy for OA. But challenges
also remain. Some of the growth factors (GFs) present in PRP
have negative effects on the OA joint. It is therefore unlikely that
a mix of GFs some of which have negative effects in the OA joint,
as present in PRP, will be of benefit in OA. Future directions of
PRP application may concentrate on seeking an appropriate and
innocuous agent like anti-VEGF antibody that can modulate and
control the effect of PRP.

INTRODUCTION
An estimated 15% of the world's population have joint

diseases; more than 39 million people in the European

Union and more than 20 million Americans have OA. By
2020, these numbers will probably be doubled 1.
When tendons and ligaments are damaged as a result of
injury or overuse, small tears may develop as part of a
condition known as tendonosis. Although these tissues are
strong and help us engage in all kinds of physical activity
when they are healthy, they do not heal well when
damaged by a sprain or by overuse, since they have a poor
blood supply.
Certain elements within the blood, specifically the
platelets and white blood cells, help tendons and
ligaments heal by stimulating a repair and growth
response that accelerates the process of developing of
new tissue. Unfortunately, the tendons and ligaments do
not receive a rich supply of these valuable nutrients, which
is why they often take a long time to heal and can cause
patients severe pain within the knee, ankle, shoulder,
wrist, bicep, calf and other areas.

What is plasma? Plasma refers to the liquid

component of blood; it is the medium for red and

white blood cells and other material traveling in the
blood stream. Plasma is mostly water but also
includes proteins, nutrients, glucose, and
antibodies, among other components.
What are platelets? Like red and white blood
cells, platelets are a normal component of blood.
Platelets alone do not have any restorative or
healing properties; rather, they secrete substances
called growth factors and other proteins that
regulate cell division, stimulate tissue regeneration,
and promote healing. Platelets also help the blood
to clot; a person with defective platelets or too few
platelets will bleed excessively from a cut.

What is platelet-rich plasma

(PRP)?
Platelet-rich plasma (PRP) is plasma with a high

concentration of platelets, which contains a large amount

of proteins. These proteins can initiate and accelerate new
tissue growth within the tendons and ligaments to repair
damage and relieve symptoms for patients with
tendonosis or other causes of chronic pain.
Injecting platelet-rich plasma into damaged tissue is an
effective yet minimally invasive treatment option used to
relieve pain and other symptoms caused by this damage.
By enhancing the bodys natural healing abilities, patients
are able to enjoy a faster and more thorough healing
process that relieves symptoms and allows them to return
to their regular activities.

What is platelet-rich plasma

used for?
Platelet-rich plasma injections can be used to treat a wide

range of orthopedic conditions, including:

Arthritis
Tendonitis
Bursitis
Joint pain
Ligament sprains or tears
Nerve inflammation
Shin splints
Plantar fasciitis
This treatment can also be used to speed the healing process
and reduce the risk of infection after cosmetic procedures or
other types of surgery.

How does this procedure work?

During the PRP injection procedure, a small amount of

blood is taken from the patient and placed in a processing

unit to separate the platelets, white blood cells and serum
from the red blood cells. The platelets and white blood
cells are then placed in a centrifuge and concentrated and
loaded into a sterile syringe. Some of the patients blood is
used as an activator and injected with the PRP into the
targeted tissue to stimulate the healing process.
This procedure is performed under local anesthetic, which
numbs the injection site to minimize pain for patients.
Most patients tolerate the injection well and experience
little to no discomfort from the injection.
Most patients require one to three PRP injections in order
to achieve the desired results from this procedure. Your
doctor will evaluate your condition a few weeks after the
initial treatment to determine whether or not additional
injections are needed. This treatment can be combined
with exercise or physical therapy in patients with acute
injuries.

Creating PRP

PRP is prepared by withdrawing peripheral blood and by

centrifugation to obtain a highly concentrated sample of

platelets. The platelets undergo degranulation to release
GFs with healing properties. The plasma contains cytokines,
thrombin, and other GFs, with inherent biological and
adhesive properties.
The first report of PRP preparation was in the 1970s 5. A few
years later, attention was drawn to gravity forces and times
of centrifugation to separate whole blood, which is crucial
for platelet counts and volume. Then the focus was on
platelet content of the PRP with an objective standard. With
the platelet activation method proposed in the last decade,
study of the various GFs released from activated PRP
became popular, and preparation was diversified. Although
peripheral venous blood factors influence the contents of
the final PRP product, platelet activation was confirmed to
be a key point in platelet counts and GFs: how to obtain
more platelet counts with a small volume of PRP, how to
improve the concentration of GFs released by PRP and
which methods can bring about sustained release of GFs 6.

The most basic method to prepare PRP is centrifugation,

divided into a one-step and two-step-centrifugation protocol.

The effect of separation by these two methods is still
controversial. According to discarded and retained
components, PRP is divided into different categories. The
increase in commercial applications led to the development of
PRP kits. Whether PRP is prepared by manual centrifugation
or by use of kits, platelet concentration is significantly higher
than in whole blood. However, the concentration of platelets
obtained by each method still differs. In addition, platelet
content is affected by the donor's gender (higher with female
than male plasma) and personal physical aspects but not age.
In contrast, the GF content is not influenced by age or gender.
Even the content might differ in the same individual with use
of different systems or different manufacturers.

The GFs will release after exogenous or endogenous

activation. Different methods of activating PRP

probably affect the concentration of GFs. PRPs are
commonly activated by calcium chloride, thrombin,
chitosan and batroxobin. Calcium chloride and
thrombin activation are the two most common
methods; 5% calcium chloride treatment for 19min
produces the most effective PRP, which have
properties for soft-tissue adhesion 7. Chitosan can be
used instead of thrombin because it enhances
aggregation, adhesion and expression of alphagranule membrane glycoprotein. Furthermore,
scaffolds by freeze-drying PRP with chitosan gel can
produce sustained release of GFs6. This potential
contributes to the durability of GFs in clinical and
experimental studies. As well as platelet content,
concentration of GFs differs between each person.

PRP for clinical application in OA

The healing process of OA comprises three phases:
(1) inflammation, (2) cell proliferation, and (3)

remodeling. Regenerative therapy involves

injecting a small volume of solution into multiple
sites of painful ligaments and tendons and
adjacent joint spaces to reduce pain and promote
tissue repair and growth. PRP was designed for this
purpose. It theoretically augments tissue healing
through the natural healing cascade. GFs are
released from the granules of platelets and induce
chemotaxis, cell migration, angiogenesis,
proliferation, differentiation, and matrix
production. PRP also enhances HA secretion and
increases release of angiogenic GFs33and36

Fig. 1Two-step-centrifugation protocol. The first centrifugation separate out the red blood cells and the second centrifugation to
concentrate the platelets. Growth factors were released from platelet products.

Y. ZhuY. Zhu, M. YuanY. ZhuY. Zhu, M. Yuan, H.Y. MengY. ZhuY. Zhu, M. YuanY. ZhuY. Zhu, M. Yuan, H.Y....
Basic science and clinical application of platelet-rich plasma for cartilage defects and osteoarthritis: a review
Osteoarthritis and Cartilage, Volume 21, Issue 11, 2013, 1627 - 1637
http://dx.doi.org/10.1016/j.joca.2013.07.017

What can patients expect after

the PRP procedure?
After platelet-rich plasma injections, patients

may experience soreness and aching for

several days, which is a sign that the healing
process has begun. Over-the-counter antiinflammatory medications may be taken if
needed to help alleviate these symptoms.
Patients can return to work and other normal
activities immediately after treatment, but
should refrain from heavy lifting and
strenuous activity for a few days.

PRP application
in the clinic
Treatment
/procedur
Symptom
e

Time

Outcome

a. OA

OA

3
injections
of PRP
(5.0 mL,
2-week
intervals)

A
significant
improvem
ent in
pain,
stiffness,
function,
and the
3 and 6 Lequesne
months
Index

PRP Does Not Work for Everyone

Not all clinical studies provide evidence that PRP alleviates

osteoarthritis symptoms. In several clinical studies PRP

injections were no better than a placebo treatment. Even in
studies that do provide evidence that PRP works, not all
patients benefit.
PRP proponents assert that PRP fails to successfully treat
symptoms in some cases because of differences in PRP
formulation or injection administration - in other words,
certain changes in variables, such as PRP preparation
methods, the amount of PRP injected, and the frequency of
injections, can make the PRP less effective. Others suggest
that PRP therapy may be a passing fad that has limited value

Cost
Intra-articular injections of platelet-rich

plasma to treat osteoarthritis are considered

"experimental" by most insurance companies.
A single treatment of one joint can cost $400
to $2,000, paid out-of-pocket by the
patient.30,31 (If more than one joint is treated,
the cost increases but typically does not
double.)

Knee Osteoarthritis Treated

with PRP
Researchers studying PRP and osteoarthritis often work with patients who have

knee osteoarthritis, a condition that experts estimate will affect nearly half of all
Americans at some point during their lives. 19 Two clinical studies that examine
PRP to treat knee arthritis are described below.
One study, published in 2013, involved 78 patients with osteoarthritis in both
knees (156 knees).20 Each knee received one of three treatments: 1 PRP
injection, 2 PRP injections, or 1 placebo saline injection. Researchers evaluated
the subjects' knees 6 weeks, 3 months, and 6 months after injection. Researchers
found:
Knees treated with 1 or 2 PRP injections saw a reduction in pain and stiffness as well

as improvement in knee function at 6 weeks and 3 months.

At the 6-month mark positive results declined, though pain and function were still
better than before PRP treatment.
The group that received placebo injections saw a small increase in pain and stiffness
and a decrease in knee function.

The platelet-rich plasma used in this clinical study had 3 times the platelet

concentration of normal blood and had been filtered to remove white blood cells.

Platelet-Rich Plasma Injections Require

Precision

An experienced physician should perform the

injections. The use of imaging technology

(e.g., ultrasound guidance) ensures a precise
injection.
Precision is important because, like
viscosupplementation treatments, plateletrich plasma injections must be made directly
into the joint capsule.

Pre-Injection Precautions
The American Academy of Orthopaedic Surgeons

recommends patients adhere to the following pre-injection

guidelines:
Avoid corticosteroid medications for 2 to 3 weeks prior to
the procedure
Stop taking non-steroidal anti-inflammatory drugs (NSAIDs),
such as aspirin or ibuprofen, or arthritis medications such as
Celebrex, a week prior to the procedure
Do not take anticoagulation medication for 5 days before the
procedure
Drink plenty of fluids the day before the procedure
Some patients may require anti-anxiety medication
immediately before the procedure

Platelet-Rich Plasma Injections,

Step-by-Step
This is an in-office procedure that involves a blood draw, preparation of the PRP,

and the injection:

Blood is drawn from a vein in the patient's arm into a vial (typically 15 to 50 mL, or
less than 2 ounces of blood is needed).
The blood is processed using a centrifuge machine.
A doctor or technician prepares the centrifuged platelet-rich plasma for injection.
The affected joint area is cleansed with disinfectant such as alcohol or iodine.
If ultrasound is being used, a special gel will be applied to an area of skin near the
injection site. An ultrasound probe will be pressed against the gel-covered skin. A
live image of the joint will be projected onscreen for the doctor to see.
The patient is asked to relax; this will facilitate the injection and also can make the
injection less painful.
Using a syringe and needle, the doctor injects a small amount (often just 3 to 6
mL) of platelet-rich plasma into the joint capsule.21
The injection area is cleansed and bandaged.
The platelet-rich plasma typically stimulates a series of biological responses, and
the injection site may be swollen and painful for about 3 days.

After the PRP Injection: Immediate Follow-up

Care
Patients are advised to take it easy for a few days and

avoid putting strain on the affected joint.

Doctors may require or suggest that a patient:
Does not take anti-inflammatory pain medication;
another pain medication may be prescribed by the
doctor
Wear a brace or sling to protect and immobilize the
affected joint; a patient who receives an injection at
the ankle, knee, or hip may be advised to use crutches
Use a cold compress a few times a day for 10 to 20
minutes at a time to help decrease post-injection pain
and swelling

Patients who do not have physically demanding jobs can

usually go back to work the next day. Patients can resume

normal activities when swelling and pain decrease,
typically a few days after the injections. Patients should
not begin taking anti-inflammatory medications until
approved by the doctor.
Physical therapy
If the injection(s) is successful in reducing the patient's
pain, the patient will likely be prescribed physical therapy.
Doing simple exercises to build and maintain muscle
strength around the affected joint serves to decrease
osteoarthritis symptoms and can slow down or halt further
joint degeneration.