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[Prevention of joint damage in hemophilic children with early prophylaxis]
W Kreuz1, C Escuriola Ettingshausen, M Funk
1Zentrum der Kinderheilkunde und Jugendmedizin, Johann Wolfgang Goethe Universität, Frankfurt/Main.
Insights
Early prophylactic treatment for hemophilia A and B is crucial. Starting prophylaxis before or shortly after the first joint bleed prevents irreversible joint damage and halts the progression of hemophilic arthropathy.
Area of Science:
- Orthopedics
- Hematology
- Pediatrics
Background:
- Severe and moderate hemophilia A and B patients are at high risk for joint damage.
- Long-term prophylactic treatment is a standard care for hemophilia patients.
- The optimal timing for initiating prophylaxis and its impact on joint health remain critical areas of investigation.
Purpose of the Study:
- To investigate the radiological and orthopaedic outcomes in severe and moderate hemophilia A and B patients.
- To evaluate the influence of the age of onset of prophylaxis and the number of prior joint bleedings on long-term outcomes.
- To determine the effectiveness of prophylactic treatment in preventing or halting the progression of hemophilic arthropathy.
Main Methods:
- Prospective investigation of 21 severe and moderate hemophilia A and B patients.
- Patients were divided into three groups based on the age of prophylaxis initiation (0-2 years, 3-6 years, and >6 years).
- Radiological and orthopaedic joint assessments using World Federation of Haemophilia (WFH) scores were performed, alongside recording joint bleeding history before and during prophylaxis.
Main Results:
- Patients initiating prophylaxis within the first two years of life (Group I) showed preserved joint health with minimal to no radiological or orthopaedic alterations.
- Patients starting prophylaxis later (Groups II and III) exhibited worsening joint scores despite ongoing treatment, with significant joint damage observed in those with a history of more than six prior joint bleeds.
- While prophylaxis significantly reduced joint bleeding frequency in Groups II and III, it could not reverse or arrest existing osteoarthropathic changes.
Conclusions:
- Early initiation of prophylactic treatment (before or shortly after the first joint bleed) is essential for preventing irreversible joint damage in hemophilia A and B.
- A history of multiple joint bleeds prior to prophylaxis initiation is associated with progressive and irreversible osteoarthropathic alterations, leading to hemophilic arthropathy.
- Effective prophylaxis must be implemented early to prevent the onset and progression of hemophilic arthropathy.
Abstract:
Radiological and orthopaedic outcome in severe and moderate haemophilia A and B patients undergoing long-term prophylactic treatment were prospectively investigated focusing on the age of onset of prophylaxis and the number of joint bleedings prior to treatment. We report on 21 patients with severe and moderate haemophilia A and B receiving prophylactic treatment of between 3.1 and 16.1 years duration. Three patient groups were evaluated according to the age at onset of prophylaxis. In group I (n = 8) prophylactic treatment was initiated in the first 2 years of life. Patients of group II (n = 6) received prophylaxis at the age of 3-6 years. Late-onset or secondary prophylactic treatment was started at the age of 6 years and above in 7 patients (group III). All patients received virus-inactivated F VIII or F IX concentrates at dosages of 30-40 IU, in some cases up to 50 IU/kg body weight i.v. three times per week for those with haemophilia A and twice per week for those with haemophilia B. Elbow, knee and ankle joints were investigated at 3-4 yearly intervals according to the radiological and orthopaedic scores recommended by the World Federation of Haemophilia (WFH). The total number of joint bleedings before and after start of prophylaxis were recorded in all patients. In group 17 out of 8 patients had unaffected joints with constant radiological and orthopaedic scores of zero or 1, after a median of 11.25 years of prophylactic treatment. One patient in this group demonstrated mild radiological alterations (score 4). Patients of group II showed neither radiological nor orthopaedic alterations at study entry. Worsening joint scores could be detected despite ongoing prophylaxis after the 3-year interval (median orthopaedic score 4, median radiological score 8). Treatment group III already showed considerable joint damage at study entry with a median radiological score of 11 (0-33) and a median orthopaedic score of 4 (0-11). Despite prophylactic treatment both, orthopaedic (median 8, range 2-12) and radiological scores (median 19.5, range 2-47) deteriorated after 3 years. Prior to onset of prophylaxis no or only one joint bleeding occurred in treatment group I. In group II, a median of 6 joint bleeds (range 1-8) were reported before prophylaxis was started. Patients of group III usually experienced a median of more than 10 joint haemorrhages (range 6-10 or more). Under prophylactic treatment the number of joint bleedings decreased significantly in groups II and III. However, radiological and orthopaedic scores increased as a sign of progressing osteoarthropathic alterations in patients reporting more than 6 joint haemorrhages before onset of prophylaxis whereas no joint alterations could be assessed in patients with no or only one joint bleeding episode prior to prophylaxis. Even a small number of joint bleedings seems to cause irreversible osteoarthropathic alterations leading to haemophilic arthropathy. Once apparent, further progression of joint damage could not be arrested despite of prophylactic treatment (group II and III). In order to prevent haemophilic arthropathy, effective prophylaxis should be started before or at least after the first joint bleeding in severe haemophilia A and B.