Low-Cost Platelet-Rich Plasma Injection for the Management of Hemarthropathy
Phase: NA
Conditions: Hemarthrosis, Hemophilia
Sponsor: University of Utah

Low-Cost Platelet- Rich Plasma for Hemearthropathy 
NCT06543368 
May 2, 2024 

STUDY PROTOCOL 
Objectives 
Hemophilic arthropathy, or hemarthropathy, results from recurrent accumulation of blood in the joints, leading 
to chronic pain, inflammation, and progressive joint damage. Effective nonsurgical treatment options for 
patients with hemophilic arthropathy are needed, but further research must be conducted to identify if safe 
conservative options, such as platelet-rich plasma (PRP) injections, can contribute to functional improvements 
and pain relief for this clinical population. 
The objective of this study is to assess the feasibility of utilizing low-cost platelet-rich plasma (LC-PRP) 
preparation technique within the context of utilizing PRP for the treatment of hemophilic arthropathy. 
Specifically, this study aims to demonstrate the safety of this technique/treatment (no serious adverse events), 
evaluate LC-PRP composition (i.e., to assess if the prepared LC-PRP has similar cellular composition to 
reported values from commercially available PRP kits), and to measure patient improvement (e.g., pain, 
function, and satisfaction) following LC-PRP injection.  
More specifically, this study will be guided by the following aims: 
Aim 1: Prospectively evaluate clinical outcomes in a cohort of patients with bleeding disorders for pain and 
functional measures over six months. Hypothesis: Subjects who receive LC-PRP will demonstrate 
improvements in pain and function at three months, specifically on the WOMAC score (knee), American 
Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot score (ankle), and the Quick Disabilities of Arm 
Shoulder and Hand (QuickDASH) score (elbow).   
Aim 2: Evaluate the total cost of the procedure, including the cost of supplies, staff time, and pharmaceutical 
components. Hypothesis: The total cost of the procedure will be comparable to the standard-of-care injection, 
corticosteroid. 
Aim 3: Evaluate the likelihood of adverse events related to the procedure, namely repeat bleeding into the joint 
or infection following the procedure. Hypothesis: Subjects who receive a LC-PRP injection will not have an 
increased risk of adverse events compared to the standard-of-care injection, corticosteroid. 
METHODS 
Study Design 
This single-arm, prospective cohort pilot study is designed to evaluate the feasibility of using LC-PRP to treat 
pain and dysfunction from hemarthropathy. Consecutive patients eligible for a standard-of-care injection will be 
enrolled from the Utah Center for Bleeding and Clotting Disorders. A total of 20 joints (estimated 10-15 
patients) will receive PRP injections, performed at day 0 and 3 weeks, for a total of two injections – two 
injections have demonstrated superior outcomes to one,1 and will increase our number of injections to improve 
the proof of feasibility. 
Sample 
Adult patients with symptomatic hemarthropathy of the ankle, knee, or elbow, based on radiographs within the 
last 24 months will be eligible for inclusion. Patients must have failed at least six weeks of conventional 
conservative treatments (e.g., medication or physical therapy). Exclusion criteria will include recent (last two 
years) surgery to the affected joint, prior joint replacement, prior orthobiologic injection into the affected joint, 
thrombocytopenia, inability to receive factor prior to PRP injection, active systemic or local infection at the site 
of injection, non-ambulatory patients, body mass index (BMI) over 50, and recent (six month) or current 
corticosteroid injection/intake. Patients with hemarthropathy in multiple joints will be eligible for up to 2 joints if 
multiple fit the criteria. 
LC-PRP Preparation 
The full methodology is presented in the Appendix. To summarize, 45mL of blood will be collected and 
processed to result in 3-9 mL of neutrophil-poor PRP, depending on the joint injected (i.e., 3 mL for 
ankles/elbows, 9 mL for knees). Whole blood will be collected into three 20 mL syringes containing ACD-A 
anticoagulant. No platelet activators will be used in this process. The flange and the plunger of the syringes will 
be clipped off with shears and placed into a centrifuge with counterbalance. The centrifuge will run at 750 G for 

five minutes. The three syringes will then be removed, and each will be consecutively attached to a 3-way 
stopcock. For each syringe, the platelet-poor (upper) portion of the plasma will be directed to a waste syringe, 
then the remaining platelet-rich (lower) portion of the plasma will be directed to a syringe containing the final 
PRP. This process will be repeated for the 3 syringes. No more than 5 minutes will elapse between stages of 
the procedure. No more than 30 minutes will elapse between completion of PRP preparation and injection; 
during that time, the PRP will be placed on a rocker to avoid layer separation. Blood will not be exposed to air 
at any point during this process, and all connections between syringes will be accomplished via Luer-Lok. PRP 
preparation/processing time will be monitored. 
LC-PRP Injection 
Peri-procedure factor management (if applicable) will be directed by the participant's primary hematologist. 
Injections are to be performed on day 0 and at 3 weeks, for a total of two injections per joint. This process will 
involve an ultrasound-guided intra-articular knee, ankle, or elbow injection by an experienced sports medicine 
provider (PI Daniel Cushman) with a 23 g needle after local anesthesia with 1% lidocaine to the extra-articular 
structures, namely the skin and joint capsule, to increase comfort.  
Blood Analysis: LC-PRP Composition 
All subjects will have less than 1mL of their whole blood and prepared PRP analyzed, with a complete blood 
count (CBC) with differential for each injection. Importantly, we will include all data required in the PRP 
minimum reporting standards,2 including “platelet, differential leukocyte, and red cell analysis of all samples.”  
Questionnaires 
We will collect demographic information along with baseline and follow-up (i.e., 1 month, 3 months, and 6 
months following second injection) patient reported outcomes, namely the WOMAC (knee), FAOS (ankle), and 
the QuickDASH (elbow). Surveys will be administered, and data will be stored, in REDCap.3–5 Additionally, 
patient surveys will assess any adverse events, pain, global satisfaction, global injection satisfaction, and 
medications. At 3 and 6 weeks, we will inquire about adverse events related to the procedure, monitoring 
closely for any reported joint bleeds or infections following PRP injections. 
DATA ANALYSIS 
Statistical Analysis Plan 
Whole blood and LC-PRP outcomes (e.g., platelet concentration, platelet count) will be summarized with 
descriptive statistics (i.e., mean and standard deviation). Patient reported outcome measures (e.g., global 
assessment, EQ-5D, WOMAC [including total score and pain, stiffness, and function subscores], QuickDASH, 
FAOS) will be described via median and interquartile range (IQR) at baseline and follow-up (i.e., 1, 3, and 6-
months). Frequencies and percentages will be used to summarize patient satisfaction with the study joint (at 
baseline and all follow-up points) and adverse events. As this is a feasibility study and therefore is not 
intentionally powered for clinical outcomes, no statistical hypothesis testing will be performed. See example 
tables 1 through 6 below for further details pertaining to planned analyses and study reporting. 
Example Table 1: Demographics 
  
n 
% 
Mean 
SD 
Total patients 
Joints 
 
 
 
 
Elbows 
Knees 
 
 
 
 
Ankles 
 
 
 
 
Age 
Body mass index (kg/m2) 
Duration of symptoms (y) 
 
 
 
Sex 
 
 
 
Female  
Male 
 
 
 
 
Hemophilia type 
 
 
 
 

Hemophilia type A 
 
 
 
 
Hemophilia type B 
 
 
 
 
Hemophilia severity 
 
 
 
 
Mild 
 
 
 
 
Moderate 
 
 
 
 
Severe 
 
 
 
 
Baseline satisfaction with joint 
 
 
 
 
Very unsatisfied 
 
 
 
 
Unsatisfied 
 
 
 
 
Neither satisfied nor unsatisfied 
 
 
 
 
Satisfied 
 
 
 
 
Very satisfied 
 
 
 
 
 
Example Table 2: Whole blood and PRP cellular composition  
Whole blood 
PRP 
Mean 
SD 
Mean 
SD 
Volume 
 
 
 
 
Platelet concentration, 103 per uL 
Platelet count (billion) 
Platelet extraction (%) 
Concentration factor 
 
WBC concentration, 103 per uL 
 
 
 
 
- 
Neutrophils 
 
 
 
 
- 
Lymphocytes 
 
 
 
 
RBC concentration, 106 per uL 
Hb concentration, g/dL 
 
Example Table 5. Satisfaction with study joint at baseline and and follow-up 
 
Baseline 
1 Month 
3 Months 
6 Months 
Satisfaction with Joint 
 
 
 
 
Very unsatisfied 
 
 
 
 
Unsatisfied 
 
 
 
 
Neither satisfied nor unsatisfied 
 
 
 
 
Satisfied 
 
 
 
 
Very satisfied 
 
 
 
 
 
Example Table 6. Adverse events associated with study PRP injections. 
 
n (%) 
Adverse Event 
 
New joint bleed 
 
Increased pain in the joint 
 
Bruising 
 
Fever/Chills 
 
Redness in the area 
 
Reduced joint range of motion 
 
Other 
 
 
 
 

REFERENCES 
 
1. 
Tavassoli M, Janmohammadi N, Hosseini A, Khafri S, Esmaeilnejad-Ganji SM. Single- and double-dose 
of platelet-rich plasma versus hyaluronic acid for treatment of knee osteoarthritis: A randomized 
controlled trial. World J Orthop. 2019;10(9):310-326. doi:10.5312/wjo.v10.i9.310 
2. 
Chu CR, Rodeo S, Bhutani N, et al. Optimizing Clinical Use of Biologics in Orthopaedic Surgery: 
Consensus Recommendations From the 2018 AAOS/NIH U-13 Conference. Journal of the American 
Academy of Orthopaedic Surgeons. 2019;27(2):e50-e63. doi:10.5435/JAAOS-D-18-00305 
3. 
Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture 
(REDCap)—A metadata-driven methodology and workflow process for providing translational research 
informatics support. J Biomed Inform. 2009;42(2):377-381. doi:10.1016/j.jbi.2008.08.010 
4. 
Harris PA, Taylor R, Minor BL, et al. The REDCap consortium: Building an international community of 
software platform partners. J Biomed Inform. 2019;95:103208. doi:10.1016/j.jbi.2019.103208 
5. 
McAlindon TE, Bannuru RR, Sullivan MC, et al. OARSI guidelines for the non-surgical management of 
knee osteoarthritis. Osteoarthritis Cartilage. 2014;22(3):363-388. doi:10.1016/j.joca.2014.01.003 
  
 
 

APPENDIX – LOW-COST PLATELET-RICH PLASMA (LC-PRP) PREPARATION METHOD 
Step  
1 
Ensure name and date-of-birth of subject. 
2 
Put stickers on all syringes, ensuring proper name & DOB throughout procedure 
3 
Add 2mL of ACD-A into 3 x 20mL syringes 
4 
Venipuncture using butterfly needle 
5 
Draw 13mL blood (15mL total including 2mL ACD-A) into 20mL syringe - syringe 1 
6 
Draw 13mL blood (15mL total including 2mL ACD-A) into 20mL syringe - syringe 1 
7 
Draw 13mL blood (15mL total including 2mL ACD-A) into 20mL syringe - syringe 1 
8 
Draw 1-2mL blood into 5mL syringe for complete blood count (CBC) testing 
9 
If extra blood is drawn up on any needle, properly dispose of extra blood to leave exactly 15mL 
10 
Cap each syringe (qty 4) - 3 for PRP and 1 for CBC 
11 
Mix all syringes by themselves with a rocking motion, back and forth 
12 
Using shears, cut off the plunger and both flanges from each syringe 

13 
Place syringes in the centrifuge, opposite each other 
14 
A fourth syringe will be used as a counterbalance, filled with saline 
15 
Using a scale, syringes will be emptied (~0-0.5mL) to match weights for counterbalance 
16 
Close centrifuge lid 
17 
Centrifuge at 750G for five minutes  

18 
Ready stopcock - one "waste" syringe (20mL) and one "PRP" syringe (10mL) 
19 
For each of 3 syringes, perform the following: 
20 
- Hold syringe upright and attach to bottom of stopcock 

21 
- Distribute upper portion of plasma into "waste" syringe, leaving 3mL of plasma 
22 
- Rotate stopcock from "waste" syringe to "PRP" syringe 
23 
- Distribute remaining 3mL of plasma into "PRP" syringe 
24 
This will leave 9mL in the "PRP" syringe 
25 
Mix syringe with rocking motion (to ensure homogeneity) 
26 
From the "PRP" syringe, inject 1mL into separate 5mL syringe for CBC testing 
27 
This will leave 8mL in the "PRP" syringe 
28 
Physician will perform injection after local anesthetic administration, name/DOB verification, and 
sterile preparation 
29 
Perform CBC testing on both PRP and whole blood samples 
 
 
Important points to note: 
1. Sterility will be ensured 
2. Appropriate storage of sodium citrate 
3. Will not use single-use vials multiple times 
4. Will use gloves and mask at all times 

5. Only use sterile syringes, stopcocks, needles 
6. Filling syringes to exact amounts is imperative.  Will avoid over- or under-filling. 
7. If a syringe becomes contaminated in any way, it will be disposed of appropriately and not continue to 
use it in the PRP preparation process. 
8. All blood must have a label on it to ensure that no patient receives another patient’s blood 
 
Supplies: 
• 
Alcohol wipes 
• 
Gloves 
• 
Elastic tourniquet 
• 
Butterfly/winged infusion set 
• 
20 mL BD syringes (dual ribbed) 
• 
18G blunt tip filling needles 
• 
Anticoagulant (single use vials): 4% sodium citrate  
• 
50cc conical tubes 
• 
Red caps 
• 
Shears 
• 
3-way stop cock 
• 
Injection syringe with needle 
• 
Centrifuge