Thesis Protocol Presentation (2_30 Pm Wednesday) shashank

8/12/2019 Thesis Protocol Presentation (2_30 Pm Wednesday) shashank

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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_plasma


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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_injury


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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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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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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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,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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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

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Thesis Protocol Presentation (2_30 Pm Wednesday) shashank

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