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.

Eligibility Criteria:
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.