WHEN SHOULD PROPHYLACTIC TREATMENT IN PATIENTS WITH HEMOPHILIA-A AND HEMOPHILIA-B START - THE GERMAN EXPERIENCE

Radiological and orthopaedic outcome in severe and moderate haemophili a A and B patients undergoing long-term prophylactic treatment were pr ospectively investigated focusing on the age of onset of prophylaxis a nd the number of joint bleedings prior to treatment. We report on 21 p atients with severe and moderate haemophilia A and B receiving prophyl actic treatment of between 3.1 and 16.1 years' duration. Three patient groups were evaluated according to the age at onset of prophylaxis. I n 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 yea rs. Late-onset or secondary prophylactic treatment was started at the age of 6 years and above in seven patients (group III). All patients r eceived 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 haemoph ilia A and twice per week for those with haemophilia B. Elbow, knee an d ankle joints were investigated at 3-4-yearly intervals according to the radiological and orthopaedic scores recommended by the World Feder ation of Haemophilia. The total number of joint bleedings before and a fter start of prophylaxis were recorded in all patients. In group I 7/ 8 patients had unaffected joints with constant radiological and orthop aedic scores of zero or i, after a median of 11.25 years of prophylact ic treatment. One patient in this group demonstrated mild radiological alterations (score 4). Patients in group II showed neither radiologic al 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 s tudy entry with a median radiological score of 11 (0-33) and a median orthopaedic score of 4 (0-11). Despite prophylactic treatment, both ra diological (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 grou p II, a median of six joint bleeds (range 1-8) was reported before pro phylaxis was started. Patients in group III usually experienced a medi an of more than 10 joint haemorrhages (range 6-10 or more). Under prop hylactic treatment the number of joint bleedings decreased significant ly in groups II and III. However, radiological and orthopaedic scores increased as a sign of progressing osteoarthropathic alterations in pa tients reporting more than five joint haemorrhages before onset of pro phylaxis whereas no joint alterations could be assessed in patients wi th no or only one joint bleeding episode prior to prophylaxis. Even a small number of joint bleedings seems to cause irreversible osteoarthr opathic 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 haemop hilic arthropathy, effective prophylaxis should be started before or a t least after the first joint bleeding in severe haemophilia A and B.