When should prophylactic treatment in patients with haemophilia A and B start?--The German experience.
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 prophylactic treatment was initiated in the first 2 years of life. Patients in group II 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 seven patients (group III). All patients received virus-inactivated F VIII or F IX concentrates at dosages of 30-50 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. The total number of joint bleedings before and after start of prophylaxis were recorded in all patients. In group I 7/8 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 in group II showed neither radiological nor orthopaedic alterations at study entry. Surprisingly, 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 radiological (median 19.5, range 2-47) and orthopaedic scores (median 8, range 2-12) 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 six joint bleeds (range 1-8) was reported before prophylaxis was started. Patients in 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 five joint haemorrhages 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 (groups 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.
Kreuz
W
W
Centre of Paediatrics, Department of Haematology and Oncology, Johann Wolfgang Goethe University Hospital, Frankfurt am Main, Germany.
Escuriola-Ettingshausen
C
C
Funk
M
M
Schmidt
H
H
Kornhuber
B
B
D000293:Adolescent; D000367:Age Factors; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D005164:Factor IX / Q000008:administration & dosage*; D005169:Factor VIII / Q000008:administration & dosage*; D005858:Germany; D006467:Hemophilia A / Q000503:physiopathology* / Q000517:prevention & control*; D002836:Hemophilia B / Q000503:physiopathology* / Q000517:prevention & control*; D006801:Humans; D007223:Infant; D011446:Prospective Studies; D016896:Treatment Outcome
D005169:Factor VIII; D005164:Factor IX