Dr. Xavier Casanova Canals. Upper Extremity Orthopaedic and Trauma surgeon in EGARSAT.

PRP (platelet rich plasma) injections can prevent surgical treatment of lateral epicondylitis: Prospective analysis of 48 patients in work compensation environment

1. !

Dr. Xavier Casanova Canals"
ORTHOPAEDICS AND TRAUMATHOLOGY DEPARTMENT"
UPPER LIMB SURGERY UNIT"
EGARSAT!
!

2. 1. What is there about PRP and
Epycondylitis?"
2. Our results: prospective study in
workers"

3. INTRODUCTION
“Tennis Elbow”"
• Prevalence 1-3% (45-55y) !
" "14,5% streneous jobs"
REPETITIVE MICROTRAUMATISM: "
• Angiofibrobastic Hyperplasia!
! NO INFLAMATORY CELLS "
" """ (Nirschl 2003)!
ECRB!
Nirschl RP, Ashman ES. Elbow tendinopathy: tennis
elbow. Clin Sports Med 2003;22:813-836.!

4. TREATMENT" RESULTS" PROBLEM"
WAIT AND SEE" 83% recovery after 8-12M (acute)"
sports medicine?!
work compensation?!
SPLINTS" no diferences wrist/forearm! combined with other treatments!
PHYSICAL THERAPY" satisfaction early time points! Lomg Therm outcomes?? !
ULTRASOUND" contradictory studies! combined with other treatments!
AINE`s ORAL / TOPIC" Initial treatment , Adverse effects!
ANESTHETIC +
CORTICOID
INJECTION"
90% symptoms improvements at 4weeks,!
no differences at 1 year with naproxen or placebo!
skin problems!
NO LONG THERM EFFECT"
BOTULINUM TOXIN" improvement at 6 and 18 weeks!
finger paresis, extension weakness!
NO LONG THERM EFFECT!
AUTOLOGOUS
BLOOD"
good results 1 injection!
excel.lent with 2-3 injections!
NO long therm studies!
ESWT" little benefit compared with other treatments! morbidity (skin lesions, haematoma, swelling)!
ACCUPUNCTURE" short therm pain relief! NO LONG THERM EFFECT!
LASER THERAPY" no efficacy compared to placebo!
SURGERY "
(open, percutaneous,
arthroscopic)"
failure conservative treatment!
73% symptom resolution!
97% return to work!
agressive treatment!
(5y) 9% moderate to severe pain!
(5y) 28% low grade symptoms!
F. Faro, MD, J. M. Wolf, MD. Lateral
Epicondylitis: Review and current
concepts. J Hand Surg 2007;32A:1271-1279)!
…although the treatment of LE has evolved, the response
(and nonreponse) to the multiple nonoperative and surgical
interventions in lateral epincondylitis indicate that our
understanding of the disease process is currently
incomplete… (Faro F., et al. 2007)!

5. Another treatment for lateral
epicondylitis…"
PLATELET "
RICH "
PLASMA"
(PRP)"

6. PRP:
BASIC SCIENCE
IN VITRO + IN VIVO"
(2 studies)"
2/2 cell proliferation!
GF expression!
Collagen expression!
Fiber organization!
!
Human tenocytes!
Sheep / Mice!
PRP CONFERS SEVERAL EFFECTS ON TENDON MODELS COMPARED WITH A CONTROL"
(LIMITATIONS)"
379 studies database searching➯ 31 studies fit “inclusion criteria”, control group"
IN VIVO"
(14 studies)"
8/13 earlier healing"
8/13 longitudinal organization"
!
3/3 [GF]0"
3/3 vascul/blood flow!
4/4 collagen deposition!
3/4 load to failure"
!
Animal (white rabbit 57%)!
Achilles / Patellar tendon!
IN VITRO"
(15 studies)"
8/9 cell proliferation!
7/8 GF levels!
4/5 collagen expression!
Tenocytes or tendon stem cells!
7 animal/7 human!

7. PRP: RANDOMIZED CLINICAL TRIALS
Mishra"
(2006)"
Peerbooms"
(2010)"
Gosens"
(2011)"
Thanasas"
(2011)"
Krogh"
(2013)"

8. Study"
Mishra!
(2006)"
Peerbooms!
(2010)"
Gosens!
(2011)"
Thanasas!
(2011)"
Krogh!
(2013)"
Design"
Pilot trial!
Level 2!
RCT!
Double blind!
Level 1!
RCT!
Double blind!
Level 1!
RCT!
Single blind!
Level 1!
RCT!
Single blind!
Level 1!
Group of
patients"
CHRONIC"
>3m!
!
VAS>6!
CHRONIC"
>6m!
!
VAS>5!
CHRONIC"
>3m!
!
VAS>5!
CHRONIC"
>3m!
!
!
CHRONIC"
>3m!
!
N"
20"
15 PRP!
5 Bupi!
100"
51 PRP!
49 CORT!
100"
51 PRP!
49 CORT!
28"
14 PRP!
14 Blood!
60"
20 PRP!
20 CORT!
20 SS!
PRP"
(BIOMET GPS
SYSTEM)"
1A"
NO Activ"
2-3mL"
+Bupi (sc)"
1A"
NO Activ"
1mL"
+Bupi (mixed)"
1A"
NO Activ"
1mL"
+Bupi (mixed)"
1A"
NO Activ"
3mL"
US guidance"
2A"
NaHCO3"
3mL"
Lido (sc)"
RHB"
(weeks)"
4w RHB!
!
4w RHB!
!
Progressive
sustained
improvement!
!
better than Cort
at 2y !
!
4w RHB!
better than Blood
short therm!
!
No RHB!
PAIN"
statistical
differences"
FUNCTION
statistical
differences"
⇓VAS"
8w - 60%"
6m - 81%"
2y - 93%"
Improve
Mayo Score
72% 6m"
⇓VAS"
1y - 73%"
(vs 49%)"
⇓DASH"
1y - 73% "
(vs 51%)"
⇓VAS"
2y- 76,5%)"
⇓DASH"
2y -72,5%"
⇓VAS "
only 6w"
NO"
Liverpool
Elbow
Scrore"
"
PRTEE: NO DIF at 3m"
postinf pain PRP > SS > Cort"
duration PRP,,SS > CORT"
"
“Any attempt to generalize about the value of PRP based on a
methanalysys of the literature would be difficult. There are simply too
many different application techniques and poor documentation of what
was actually given to the subjects”. !
!
Mishra et al. Platelet rich plasma and upper extremity. Hand Clin
2012;28:481-491.!

9. PRP: CLASSIFICATION
TYPE"
WHITE BLOOD
CELLS"
ACTIVATION"
PLATELET
CONCENTRATION"
1!
INCREASED! NO!
A>5XPLATELETS!
!
B<5XPLATELETS!
2!
INCREASED! YES!
3!
NO/MINIMAL! NO!
4!
NO/MINIMAL! YES!
Mishra A, Harmon K, Woodall J et al. Sports medicione applications of platelet rich
plasma. Curr Pharm Biotechnol 2012;13(7):1185-95.!
Mazzoca AD et al. The positive effects of different platelet rich plasms methods on
human muscle, bone, and tendon cells. Am J Sports Med 2012;40:1742-49. !
• Varying preparations of PRP had different in vitro effects on proliferation
and GF expression in tenocytes, osteoblasts and myocytes.!
Dragoo JL et al. Comparison of the acute inflammatory response of two comercial platelet
rich plasma systems in healthy rabbit tendons. Am J Sport Med 2012;40:1274-81.!
• The effect of leukocyte concentration is poorly understood. !

10. > 800 proteins"
>16 separation systems "
Boswell SG, D.V.M, Cole BJ, MD, et al. Platelet
Rich Plasma: A milieu of bioactive factors.
Arthroscopy 2012; 28:429-439.!
!
Foster TE et al. Platelet-Rich Plasma from
basic science to clinical applications. Am J
Sport Med 2009; 37(11):2259-2272.!

12. 2. Prospective analysis of 48
patients in workers’ compensation
environment

(EGARSAT)

13. HYPOTHESIS AND
OBJETIVES
HYPOTHESIS"
• PRP injections reduce pain and improve functionality enough to prevent
more agressives treatments.!
GENERAL OBJECTIVE "
"
"
SPECIFIC OBJECTIVES"
• To determine after-treatment variations in PAIN, FUNCTION, LIFE
QUALITY and GRIP FORCE.!
• To determine the proportion of patients that can prevent surgical
treatment!
• To determine the survival function !
To Determine the effectivenes of PRP injection on Chronic LE in
the general clinical practice at work compensation environment"

14. PATIENTS AND METHODS
DESIGN !
• Prospective quasi-experimental clinical study pre-post intervention without
control group.!
AMBIT AND POPULATION "
• Labor Insurance Corporation (EGARSAT) 220.000 insured workers!
INCLUSION CRITERIA" EXCLUSION CRITERIA "
Clinical diagnose of LE!
>3m chronicity"
Conservative treatment failure"
Informed consent!
!
Previous elbow surgery!
Systemic rheumatic or
Methabolic pathology!
Radiculopathy!
Elbow osseous deformity!
Complet Rupture on MRI"
Corticoid injection in last 3m"

15. *Croisier JL, Foidart-Dessalle M, Tinant F et al. An isokinetic eccentric programme for the
management of chronic lateral epicondylar tendinopathy. Br J Sports Med 2007;41:269-75 !
PATIENTS AND METHODS
!
ORTHOPAEDIC!
SURGEON!
!
REHAB.!!!
THERAPY*!
FIRST!
ASSITANCE!
WORK!
LATERAL&
EPICONDYLITIS&
NEAI& STRECHING& PRP!
WORK&REST)&
ECCENTRICAL&
EXERCISES&
SURGICAL&
PROCEDURE&
CRIOTHERAPY&
BRACE&
CORTICOID&
INJECTION&
ELECTRO&
THERAPY&

16. April 2011 – December 2012!
4 patients excluded:!
KDiscal haernia!
KLanguage!
KComplete rupture on MRI!
KBurocrathic reasons!
13 patients lost
during sample
selection!
2 pacientes reject
PRP injections!
2 abandonments
after 1
st
injection!
Flow Diagram of the study.!
PATIENTS AND METHODS

17. PRE injections! INJECTIONS! POST injections!
INCL/EXCL Criteria!
Consetment!
Data Collecting!
Blood analysis!
1st !
INJ!
2nd!
INJ!
3rd!
INJ!
1m!
Control!
3m !
Control!
6-12m !
Control!
EVA"
QDASH"
SF12"
DEXTER"
EVA"
QDASH"
SF12"
DEXTER"
15d! 15d!T0! 4m! 7-13m!Time"
Average follow-up: 7.2months!
2m!
Schedule of the study: PRP injections protocol"
PATIENTS AND METHODS

18. • T-test for paired data: "
• Comparison of pre-post response variables"
• Fisher exact test (qualitative) and U of Mann Whitney test
(quantitative)!
• Bivariate analysis: determination of the differences between
non-operated and operated subgroups in some of the studied
variables ifferences of variables!
• Kaplan-Meyer survival function !
• considering failure surgical treatment!
• STATA S/Evs9 statistical pack!
• Statistical significance p<0.05"
PATIENTS AND METHODS
STATISTICAL ANALYSIS"

19. • Anítua* methodology!
• PRP 4B Mishra"
• [platelets]= x 2-3 [PBlood]!
• Laminar flux!
• 24mL peripheral blood sample (sodic citrate)!
• Centrifugation 8`- 1800rpm!
• Activation: CaCl
2
!
*E. Anítua, MD, DDS. Plasma Rich in Growth Factors: Preliminary
Results of Usein the Preparation of Future Sites for Implants. Int J Oral
Maxilofac Implants. 1999 Jul,Aug;14(4):529,35. !
PATIENTS AND METHODS

20. PATIENTS AND METHODS
Platelet Rich Plasma "
Platelet Poor Plasma"
Leukocyte band"
Peppering Technique!
1!
4!
3!2!1!
6!
5!
3CC"
Activation CaCl
2
!
Density
gradient after
centrifugation!

21. • NO Anaesthesia!
• Paracetamol 1g/8h !
• 48h work rest!
• NO RHB associated!
PATIENTS AND METHODS

22. RESULTS
SAMPLE DESCRIPTION"
VARIABLE! MESURE! MEAN! SD! RANG!
AGE" years! 45,9" 6,6! 32 - 59!
WEIGHT" kg! 69,4" 11,4! 52 - 102!
HEIGHT" cm! 165,8" 10! 147 - 187!
PLATELETS
RECOUNT"
x10
3
/mL! 246,6" 59,2! 92 - 415!
YEARS IN
PROFESSION"
years! 15,3" 12,1! 1- 40!
SICK LEAVE
BEFORE PRP"
days! 40,4" 53,5! 0 - 251!
LE Nº
EPISODES"
episodes! 1,7" 1,1! 1 - 5!
CHRONICITY" months! 23,1" 28,9! 4 - 120!

23. 82
%
18
%
RIGHTLEFT
13%
43%
44%
NO LOADED
MEDIUM LOADED
HIGHT LOADED
25
%
75
%
SICK LEAVE
WORKING
77
%
23
%
CORTICOID INJ
NO CORTICOIDS
16
%
84
%
DOMINANT
NON-DOMINANT
60
%
40
%
MANWOMEN
AVERAGE 5.2M pre-PRP!
RESULTS

24. 0
10,25
RESONANCIA MAGNÉTICA
EDEMA (8)
PARTIALRUPTURE (9)
ARTICULAREFFUSION (6)
CARTILAGELESION (1)
OSSEOUSLESION (1)
• Irregularity, distortion and thickening of the common
extensor insertion"
• MRI severity signs do not correlate positively with
symptoms in chronic.!
Walton MJ t al.The reliability and validity of MRI in the assessment of
chronic lateral epicondylitis. J Hand Surg 2011;36A:475-79).!
RESULTS

25. Test"
1m Postinj!
(N 29)!
3m Postinj!
(N 26)!
6-12m postinj!
(N 15)!
/‡x/‡!
(sd)!
p*!
/‡x/‡
(sd)!
p*!
/‡x/‡!
(sd)!
p*!
EVA"
16,4"
(32,8)!
0,0116!
27,0"
(34,9)!
0,0003!
46,7"
(20,1)!
0,0000!
qDASH"
12,7"
(25,8)!
0,0167!
19,1"
(23,8)!
0,0007!
32,4"
(22,0)!
0,0000!
qDASH"
work"
16,1"
(28,9)!
0,0101!
28,4"
(31,3)!
0,0003!
43,6"
(21,6)!
0,0000!
SF12"
PCS"
-3,3"
(6,8)!
0,0179!
-7,8"
(9,4)!
0,0012!
-11,1"
(7,3)!
0,0000!
*p<0,05= statistical significance; !X! mean of differences PRE-POST; (sd) standar deviation"
DIFFERENCES PRE AND POST INTERVENTION!
RESULTS

26. RESULTADOS
La puntuación SF12-MCS no tiene diferencias estadísticamente significativas.!
La mejoría en la Dinamometría está en el límite de la significación estadística.!
EVA!
qDASH!
qDASH trab!
SF12 PCS!
SF12 MCS!
DEXTER!
0"
20"
40"
60"
80"
100"
120"
140"
BASAL"
1m"
3m"
6.12m"
EVA"
qDASH"
qDASH"trab"
SF12"PCS"
SF12"MCS"
DEXTER"

27. RESULTS
BIG EFFECT SIZE "
Clinical relevance of the differences !
COMPARISON !VAS PAIN! Q-DASH! SF12-PCS!
0 - 1m! 0,65!moderate!0,45!small!0,36&small!
0 - 3m! 0,96! BIG! 0,83& BIG! 0,85& BIG!
0 - 6/12m! 2,40! BIG! 1,95& BIG! 1,51& BIG!
Cohen 1988 Effect Size (d value): 0.2 small; 0.5 moderate; 0.8 big!

28. 35%
65%
IQ
NO IQ
COMPLICATIONS !
1 vasovagal syndrome!
Postinjection pain(3-5d)!
RESULTS

29. Bivariate analysis"
OP (N14) / NON-OP (N25)"
Statistical
differences?"
p*"
Number of previous LE episodes" no" 0,13!
Sick leave days before injections" no" 0,04!
Duration of symptoms before injections" no" 0,58!
Platelet count (peripheral blood)" no" 0,57!
Corticoid injection before PRP" no" 0,08!
Stop working during PRP injections" no" 0,24!
Job effort grade subjective classification" no" 0,72!
*p<0,05= statistical differences!
RESULTS

30. SURVIVAL ANALYSIS!
0.00
0.25
0.50
0.75
1.00
0 20 40 60 80
analysis time
Kaplan-Meier survival estimate
71% conversions to surgical tretament were done during first 15w"
(4 IQ de la 15-27)!
!
60% probability of preventing surgery"
The PRP failure should be expected in 4-6 months"
RESULTS

31. LIMITATIONS
• Workers’ compensation environment: low adhesion
of patients to periodical testing while keep working!
• Losts and missings"
• Design: not controlled!
• Average Follow-up of 7,2m!
Statistical power of the comparisons pre-post between
the variables of the study (VAS, quickDash, SF12 PCS)
oscilates around 80-100%!

32. CONCLUSIONS
• The treatment of Chronic LE with PRP (4B) injections is
effective in work compensation environment improving pain
and functionality with a probability of 60% of preventing
surgery and a very low complicaction rate. !
• Is necessary to universalize the method of preparation and
adminstration of PRP and also specify the characteristics of the
product using a common classification; this will make possible
to compare its effects and results among different studies!
• More studies are needed to identify those patients who will
most probably improve with this treatment and fix its
indication according to some prognostic factors as the stage of
tendinopathy.!

33. THANK YOU

34. !

Dr. Xavier Casanova Canals"
ORTHOPAEDICS AND TRAUMATHOLOGY DEPARTMENT"
EGARSAT!
!
Head of Department: Dr. Francesc Soler i Romagosa"
!

36. PRP is a plasma suspension that contains all components of whole blood
in varying amounts (Red Cross: > 200.000/mL)*"
PRP ¿WHAT IS IT?
*Boswell SG, D.V.M, Cole BJ,
MD, et al. Platelet Rich
Plasma: A milieu of bioactive
factors. Arthroscipy 2012;
28:429-439.!

37. PRP ¿HOW IT WORKS?
CITOKINES"
INTRACELLULAR SIGNALING"
NUCLEAR GENE EXPRESSION"
Tendon healing phases!
1. INFLAMMATION !
2. PROLIFERATION !
3. REMODELING!
PROTEIN EXPRESSION (GF)"
cell proliferation"
angiogenesis"
cell chemotaxis"
cell differenciation"
extracell matrix production"
PRP Goal: positively affect gene expression and mathrix
synthesis in tendon cells (enhance healing)"
BIOLOGIC TREATMENT, CELLULAR LEVEL"
Foster TE, MD, Puskas BL, MD, Mandelbaum BR, MD et al. Platelet Rich Plasma. From basic science to
clinical applications. Am J Sports Med 2009;37(11):2259-2272.!
Boswell SG, D.V.M, Cole BJ, MD, et al. Platelet Rich Plasma: A milieu of bioactive factors. Arthroscipy 2012;
28:429-439!

38. EVA"
DASH"
PRP-group sustained improvement !
Cortocoid-group declination, higher
recurrence and reintervention rate!
26weeks!

39. RESULTS RESUME
• PRP (4B, Anítua) injections in chronic LE reduce
pain and improve function and life quality with
statistical and clinical significance !
• No major complications has been registered!
• In workers’ compensation environment 65% of cases
have not received other treatments after injections,
preventing the surgical procedure"
• It has been performed without interruption of work
activities in 75% of cases !
• The Kaplan-Meier Survival function value is 0.6
(60% probability of preventing surgery)!