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Effect of Intra-Articular Injection
Platelet-Rich Plasma in patients wit
Osteoarthritis knee
Candidate Chief GuidDr. Shashank Misra Dr. S. L. YadJR,PMR,AIIMS Professor
Department ofAIIMS
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CO-GUIDES
Dr. U Singh Dr. Sanjay Wadhwa DHanda
Professor & Head Professor
Professor
Department of PMR Department of PMR D
PMR
AIIMS, New Delhi AIIMS, New Delhi AIIM
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INTRODUCTION
Osteoarthritis (OA) is a chronic degenerative disorder of multifacharacterized by loss of articular cartilage, hypertrophy of bone
subchondral sclerosis and range of biochemical and morphologica
the synovial membrane and joint capsule
Mechanical, biochemical, and genetic factors are all involved in p
osteoarthritis
Osteoarthritis (OA) is the second most common rheumatological
most frequent joint disease with prevalence of 22% to 39% in
reference)
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INTRODUCTION
Typical clinical symptoms are pain, particularly after prolonged actbearing; whereas stiffness is experienced after inactivity
Characteristics of osteoarthritis vary across patients, and several
patterns have been identified
The choice of a suitable treatment strategy for a patient depends on
contraindications to specific therapies, and overall tolerability and
the considered treatment
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KNEE OSTEOARTHRITIS
Osteoarthritis of weight-bearing joints, such as knee osteoarthra local mechanical driven disease than a generalized one
In order to reach a non-vascularized tissue, such as cartilage
articular administration of drugs has always been considered atreatment modality
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CURRENT TREATMENT MODALIT
At present, there are numerous, non-invasive treatment ap
emphasis on pain management, improvement in function and th
modify the disease process and progress of cartilage degeneration.
Conservative management options include analgesics, steroid an
anti-inflammatory drugs, glucosamine/chondroitin supplement
therapy, and hyaluronic acid (HA) injections. Intra articular injection of glucocorticoids and viscosupplim
hyaluronic acid leads to short term pain relief that may last betwe
to few months
However, most of them have either been of short-term success,
the biological pathology or have shown only minor benefits
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NEW TREATMENT MODALITIES
Current research is aimed at investigating new methods of stimul
of damaged cartilage
Most recent knowledge regarding tissue biology highlights
regulation of growth factors for the normal tissue structure and
tissue damage
Platelet-rich plasma (PRP) therapy is a simple, low cost and minmethod that allows a natural concentrate of autologous growt
obtained from the blood
This therapy is widely experimented in different fields of med
potential to enhance tissue regeneration
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PLATELET RICH PLASMA
Platelet-rich plasma is autologous blood plasma that has been
platelets.
As a concentrated source of autologous platelets, PRP contain
through degranulation, several different growth factorsand other
stimulate healing of bone and soft tissue
Platelet rich plasma is composed of enhanced concentratio
contained in whole blood depending on the extraction proces
contains a hyper physiological content of autologous growth factor
http://en.wikipedia.org/wiki/Blood_plasmahttp://en.wikipedia.org/wiki/Platelethttp://en.wikipedia.org/wiki/Autotransplantationhttp://en.wikipedia.org/wiki/Degranulationhttp://en.wikipedia.org/wiki/Growth_factorhttp://en.wikipedia.org/wiki/Soft_tissuehttp://en.wikipedia.org/wiki/Soft_tissuehttp://en.wikipedia.org/wiki/Soft_tissuehttp://en.wikipedia.org/wiki/Soft_tissuehttp://en.wikipedia.org/wiki/Soft_tissuehttp://en.wikipedia.org/wiki/Soft_tissuehttp://en.wikipedia.org/wiki/Growth_factorhttp://en.wikipedia.org/wiki/Growth_factorhttp://en.wikipedia.org/wiki/Growth_factorhttp://en.wikipedia.org/wiki/Degranulationhttp://en.wikipedia.org/wiki/Autotransplantationhttp://en.wikipedia.org/wiki/Platelethttp://en.wikipedia.org/wiki/Blood_plasmahttp://en.wikipedia.org/wiki/Blood_plasmahttp://en.wikipedia.org/wiki/Blood_plasma8/12/2019 Thesis Protocol Presentation (2_30 Pm Wednesday) shashank
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CLINICAL APPLICATIONS OF P
In humans, PRP has been investigated and used as clinical too
types of medical treatments, including nerve injury,
osteoarthritis, cardiac muscle injury, bone repair and regenera
surgery, and oral surgery.
PRP has also received attention as a result of its use in tre
injuries in professional athletes
http://en.wikipedia.org/wiki/Nerve_injuryhttp://en.wikipedia.org/wiki/Osteoarthritishttp://en.wikipedia.org/wiki/Cardiac_musclehttp://en.wikipedia.org/wiki/Plastic_surgeryhttp://en.wikipedia.org/wiki/Oral_surgeryhttp://en.wikipedia.org/wiki/Oral_surgeryhttp://en.wikipedia.org/wiki/Oral_surgeryhttp://en.wikipedia.org/wiki/Oral_surgeryhttp://en.wikipedia.org/wiki/Plastic_surgeryhttp://en.wikipedia.org/wiki/Cardiac_musclehttp://en.wikipedia.org/wiki/Cardiac_musclehttp://en.wikipedia.org/wiki/Cardiac_musclehttp://en.wikipedia.org/wiki/Osteoarthritishttp://en.wikipedia.org/wiki/Nerve_injuryhttp://en.wikipedia.org/wiki/Nerve_injuryhttp://en.wikipedia.org/wiki/Nerve_injury8/12/2019 Thesis Protocol Presentation (2_30 Pm Wednesday) shashank
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ROLE OF PRP IN OSTEOARTHR
Recent studies support the application of platelet-rich plasma pr
effective and safe method in the treatment of the early stages of kn
Growth factors present in platelet-rich plasma produ
transforming growth factor , platelet derived growth factor, and
growth factor 1, contribute to the maintenance of a homeostastatus between anabolism and catabolism on the articular cartilage
Others such as vascular endothelial growth factor and basic fibro
factor show chondroinductive roles
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. REVIEW OF LITERATURE
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REVIEW OF LITERATURE
Mechanism of action
Platelets were thought to act solely in the clotting cascade. In addition
hemostasis at sites of vascular injury, platelets contain an abundance
factors and cytokines that are crucial in soft tissue healing and bone m
(Anitua et al., 2006)
Platelets also discharge many bioactive proteins responsible for attra
macrophages, mesenchymal stem cells, and osteoblasts, which not on
scavenging of necrotic tissue but alsofacilitate tissue regeneration and
(Sampson, 2008)
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REVIEW OF LITERATURE
The concept that application of PRP would result in impr
cartilage repair is based on the physiological role of platele
healing (Nurden et al., 2008)
There are classification schemes that categorize platelet concen
on relative concentrations of platelets, leukocytes, and fibrin, ait is important to recognize and understand that there
differences between types of platelet concentrates that are
(Dohan Ehrenfest et al., 2009)
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REVIEW OF LITERATURE
Mishra et al. (2012) supports the thought that PRP can sti
anabolism, reduce catabolic processes, and may improve overall j
reducing synovial membrane hyperplasia,demonstrating tha
mesenchymal stem cell proliferation in vitro
Dr Kisiday, et al concluded the study that suggests that
preparations may be the most advantageous for intra-articular appli
double-spin systems should be considered with caution
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REVIEW OF LITERATURE
,Baltzer et al., (1994) conducted A prospective, randomize
observer-blinded, placebo controlled trial and demonstrated
conditioned serum injections induced considerable improvemen
signs and symptoms of osteoarthritis with results that are even sup
hyaluronic acid
Sanchez et al. (2008) showed interesting preliminary results usin
injections of an autologous preparation rich in growth factors for tr
osteoarthritis Their studies suggest that these potent biologic
chondrocytes have an important role in cartilage repair
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REVIEW OF LITERATURE
Kon et al. reported results of a large, prospective case series usin
platelet rich plasma injection in patients with degenerative chondr
knee, as seen on magnetic resonance image or clear osteoarthrosis
The authors concluded that treatment with platelet rich plas
effective for improvement of pain, function, and quality of life
degenerative articular pathology
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RATIONALE OF STUDY
Pharmacological treatments options bear considerable risk of adver
events and gastrointestinal adverse effects observe for treatment o
Chronic nature of the disease requires development of drugs su
treatment with minimal side effects, which is a challenging goal.
Intra articular injection of drugs directly into the affected joint ha
option for treatment of osteoarthritis which is already frequently potential to deliver the desired profile.
PRP can stimulate chondral anabolism by stimulating chondrogenincreasing aggregan levels and promoting mesenchymal stem creduce catabolic processes, and may improve overall joint home
synovial membrane hyperplasia
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AIMS AND OBJECTIVES
Aims: To study the effect of intra- articular injections of plat
produced by single spin on improvement of pain, function, and
patients with OA knee
Objectives: The objectives of this study are to assess 1) changes inimprovement in functional outcome, and 3) improvement in qu
patients with OA knee
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STUDY CHARACTERSTICS
Study Design: A prospective, double blind, single hos
randomized control trial
Study Duration: The study shall commence after approvinstitutional review board and the ethical committee till tsample size is attained and will strictly adhere to the ICM
guidelines
Study Location:The study will be conducted at the DepartmenMedicine and Rehabilitation, All India Institute of Medical ScDelhi
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PATIENT PROFILE
Patient Selection:
Patients with chronic pain of knee failing conservative treatment by other tand imaging findings of degenerative changes of knee as classified by radioKellgren Lawrence grade I-III) after filling written consent forms and fulfilcriteria will be recruited. All male patients greater than age of 35 years wthe study except those with significant co-morbidities
Inclusion Criteria:
1) Male and female patients aged above 35 years
2) Diagnosed with OA of knee by radiograph
3) Radiologic severity kellgren lawrence scale less than grade 4
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EXCLUSION CRITERIA
Exclusion Criteria:
1. Systemic autoimmune rheumatoid disease (connective tissue diseas
necrotizing vasculitis)
2. Uncontrolled diabetes mellitus
3. Blood dyscrasias
4. Undergoing immunosuppressive therapy
5. Patient with impaired cognitive function
6. Unwilling to participate
7. H/o NSAID use within 5 days prior to blood withdrawl for PRP preparati
8. Hb < 10gm/dl and platelet count < 1,50,000 /cu.mm
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CLINICAL ASSESSMENT TES
Mention all your tests and their smallintroduction
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METHODOLOGY
Consent:Informed written consent prior to being enlisted in the stu
from each participant
History:A detailed complete history of the subject will be taken
Examination: The clinical examination will include determinat
motion and crepitus in affected knee, any malalignment with a bo
Any erythema or warmth over the affected joint(s);or any bland effuany limitation of joint motion or muscle atrophy around affect
mention your interview scales with a better language here)
Investigations: Haemoglobin/TLC/DLC/ESR levels, Blood Suga
Blood Urea/ Serum Creatinine/ Serum ALP levels. X ray both knee
and lateral views)
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Preparation and safety of PRP
Platelet rich plasma is prepared by centrifuging autologous, an
whole blood.. Centrifugation separates the following: (1) plasm
from (2) platelets and white blood cells (buffy coat, middle layer
blood cells (bottom layer) (Fig. 3.) as a result of difference
gravity.
In order to further concentrate the preparation, a second ce
separates the platelet rich plasma from platelet-poor plasma. Of
of 2 spins versus 1 spin is controversial. Although a second spin w
concentrate the platelets further, but it will deplete wbc whi
helpful in regeration of cartilage as suggested by Mishra et al
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Platelet rich plasma preparation (type 1, sin
To prepare the PRP, 24 mL of peripheral blood will be extracted from each
venipuncture directly into 4 EDTA tubes .
The extracted blood will be centrifuged at 3500 rpm for 15 minutes at roo
a system centrifuge.
Once the blood tubes will be centrifuged, we will proceed to physically sep
fractions by meticulous pipetting and under strictly sterile conditions.
We will pipette only the 2 mL of plasma rich in platelets remaining above
and the buffy coat, (one sample must be sent for analysis of platelet co
Before infiltration, all these 2-mL fractions will be put together in a single t
with gentle inversion of the tube in a sterile glass container.
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Pre-Intervention
Patients will be asked to discontinue corticosteroid use if possible
week and as long as 3 weeks before the procedure.
As for nonsteroidal anti-inflammatory drugs (NSAIDs) will be stop
extended period around the time of PRP administration and others f
preoperatively. Anti-inflammatories will not stop growth factor r
occurs almost instantly once PRP is introduced to the tissue or joint.
Normal consideration will be given to patients use of other antic
antiplatelet agents as per their standard injection protocols.
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We prepared PRP by single spin methods -
Single spin .
We spinned the venous blood of 6 ml in EDTA vial at about 3800 rminutes.We pipetted layer of about 2 ml above buffy coat. Throughcount machine ,platelet concentration was calculated which was abbase line level
The PRP Procedure (Intervention)
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The PRP Procedure (Intervention)
Clinical examination and imaging can help to characterize the prec
extent of the injury and/or degenerative disease.Ultrasound studies prior and post-therapy, document specific outco
as regeneration of tendons and evidence of tissue healing. PRP s
performed under strict asepsis.
Patients will be informed about the procedure and written consen
Analgesia and/or anxiolytics may be administered as needed.
Materials for the injection (PRP, needles, gel) will be placed on a ster
to the patient, who would have been positioned comfortably to ena
injection site.
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After the patientsskin will be cleaned and an aseptic field will
small amount of local anesthesetic (2-3 mls) may be injectedanalgesia for the PRP administration.
A test local anesthetic injection also may be administered to
source of pain and aid the physician in site selection for PRP i
analgesia following local administration helps to confirm
pathology and the source of pain).
Lidocaine will be used as the local anesthetic
Image-guided injection ( ultrasound) will be performed and will
in real time
Post-Procedure
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Post-Procedure
Patients should rest, ice the affected area and elevate the limb for 48 h
injection.
The pace and duration of rehabilitation depends on the nature and ext
and the patients overall health and condition.
Post-treatment, some patients may use a walker boot, knee brace and/
the lower extremity or a sling for the upper extremity to immobilize
Stretching and light resistance exercises and physical therapy may also
after 2-5 days.
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OUTCOME MEASURES
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STATISTICAL ANALYSIS