Platelet-Rich Plasma Intra-Articular Injection in Treating Hemophilic Arthropathy

Severe hemophilia is characterized by frequent and lifelong bleeding, with more than 60% of bleeds occurring into joints . Repeated joint bleeding leads to chronic synovitis, cartilage damage and bony destruction. Currently available treatment of hemophilic arthropathy, such as analgesics, NSAIDs, and hyaluronic acid (HA), are predominantly directed toward the symptomatic relief of pain and inflammation, but they do little to reduce joint cartilage degeneration. Platelet-Rich Plasma (PRP) is a simple and minimally invasive method that provides a natural concentrate of autologous growth factors from the blood. This method is now being increasingly applied in clinical practice to treat musculoskeletal disorders, such as tendon repairment and osteoarthritis. To the best of our knowledge, no study applies PRP for arthropathy of knee joint in hemophilia patients. The aim of the study is to investigate the efficacy, safety and duration of benefit of single PRP injection versus five weekly intra-articular injections of HA in patients with hemophilic arthropathy of knee.

Severe haemophilia is characterized by frequent and lifelong bleeding, with more than 60% of bleeds occurring into joints. Repeated joint bleeding leads to chronic synovitis, cartilage damage and bony destruction, which are associated with limitation of range of motion (ROM), pain, muscle atrophy, functional impairment, and poor quality of life. The knee, elbow, and ankle are the most commonly involved joints and arthropathy could worsen in adolescence or young adulthood. Hemophilic arthropathy is a multifactorial event and there is evidence to suggest that iron may play a major role with release of cytokines such as Interleukin ( IL)-1, IL-6, and tumour necrosis factor alpha (TNF-α) leading to chronic proliferative synovitis, hypervascularity, and progressive arthropathy. These effects on cartilage and subchondral bone are inflammatory and degenerative in nature and management of chronic hemophilic arthropathy is difficult. Currently available drugs for the treatment of hemophilic arthropathy, such as analgesics, corticosteroids, nonsteroid and steroid anti-inflammatory drugs, and hyaluronic acid (HA), are predominantly directed toward the symptomatic relief of pain and inflammation, but they do little to reduce joint cartilage degeneration. Platelet Rich Plasma (PRP) is a simple and minimally invasive method that provides a natural concentrate of autologous growth factors from the blood. This method is now being increasingly applied in clinical practice to treat musculoskeletal disorders, such as tendon repairment and osteoarthritis. Growth factors including platelet derived growth factor (PDGF), insulin growth factor (IGF), vascular endothelial growth factor, and transforming growth factor beta-1 are believed to be key components of PRP for structural repair. Although comparing PRP with other intra-articular and soft tissue injections has led to conflicting results, it seems that PRP has useful effects on healing and functional improvement of injured tissues. To the best of our knowledge, only one study applies PRP for arthropathy in haemophilia. Teyssler et al reported PRP could reduce pain of chronic ankle synovitis in hemophilia although the small sample size (n=6), short term follow-up and absence of a control group. Hyaluronic acid (HA) has some role in joint mechanical support and its metabolic effects, which causes endogenous HA synthesis, stimulation of chondrocyte metabolism, synthesis of cartilage matrix components, and inhibition of chondrodegenerative enzymes, as well as inflammatory process. In 1994 Fernandez-Palazzi et al firstly used intra-articular HA injection for haemophiliacs with arthropathy and reported its beneficial effects in 2002. Recently, Carulli et al reported 27 haemophilic patients with a mean seven-year follow-up who had excellent results in terms of pain relief and functional improvement in the knee following treatment with HA injection. Viscosupplementation is a safe and effective therapeutic strategy in haemophilic arthropathy of knee in order to delay of surgery. The aim of the study was to investigate the efficacy, safety and duration of benefit of single PRP injection versus five weekly intra-articular injections of HA in patients with haemophilic arthropathy of knee.

single intra-articular injection of 2mL PRP (RegentKit-THT-1, RegenLab SA, Mont-sur-Lausanne, Switzerland)

five weekly intra-articular injections of 2.5 mL of hyaluronate sodium (ARTZDispo, Seikagaku Corporation Japan).

The pain intensity will be evaluated subjectively on a visual analogue scale (0-10). Higher scores mean a worse outcome.

Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) From Baseline at 1, 2, 3 &6 Months

It consists of 24 items: five pertaining to pain perception, two to stiffness, and 17 to physical function. Individual scores were then summed to form a raw score ranging from 0 (best) to 2400 (worst). Finally, WOMAC total score normalized between 0 (best) and 100 (worst).

The SF-36 is a 36-item assessment tool that measures eight general health concepts including physical functioning, role limitation due to physical health problems, bodily pain, general health, vitality, social functioning, role limitation due to emotional problems, and mental health. Individual scores were then summed to form a total score ranging from 0 (worst) to 100 (best). Higher scores mean a better outcome.

Synovial thickness (mm) by ultrasonography were evaluated from the lateral, middle, and medial aspects of the anterior suprapatellar recess

Power Doppler assessment of the selected synovial sites was performed with settings standardized to a pulse repetition frequency of 700 Hz. The power Doppler gain was adjusted to a level just below the disappearance of artifacts under the bony cortex.14,15 The intensity of blood flow in the synovium was scored on a semiquantitative scale from 0-3 (grade 0, no intraarticular colour signal; grade 1, up to 3 color signals or 2 single and 1 confluent signal in the intraarticular area; grade 2, greater than grade 1 to <50% of the intraarticular area filled with color signals; grade 3, ≥50% of the intraarticular area filled with color signals)

Inclusion Criteria: hemophilia patients with hemophilic arthropathy of knee joints for at least 6 months painful (VAS ≥ 3) hemophilic arthropathy of knee joints after medication Exclusion Criteria: presence of joint infections, any surgery on the joint in preceding 12 months intra-articular corticosteroid or HA injection within the past 6 months treatment with systemic steroids history of rheumatoid arthritis, or gouty arthropathy history of chicken or egg allergy presence of neoplasm use of non steroidal anti-inflammatory drugs in the 5 days before study platelet values < 100,000/mm3 acute hemarthrosis paresis, or recent trauma.