Results of secondary prophylaxis in children with severe hemophilia

Abstract

In this study, 13 children with severe hemophilia were given routine replacement infusions of factor VIII or IX to treat arthropathy. The children who had a mean age of 6.9 years (range 2.0-12.5) at initiation of prophylaxis had experienced an average of 43 acute hemorrhages (range 8-127) in the year prior to prophylaxis, of which a mean of 24 (range 5-46) were into joints. Therapy was begun in five children, using factor VIII concentrate at 20 U/kg three times a week, and one boy received factor IX concentrate 40 U/kg twice a week. This dose schedule was inadequate for three factor VIII-deficient boys and for the one factor IX-deficient boy. Two of three factor VIII-deficient boys responded to an increase to 30 U/kg prior to the 3-day interval. The dose frequency was increased to three times a week for the factor IX-deficient boy, but he continued to bleed and was taken to synovectomy. One of the original five factor VIII-deficient boys plus seven other factor VIII-deficient boys were begun on factor VIII 20 U/kg every other day; 3 boys ceased bleeding. Trough factor VIII levels were measured 24 hr after an infusion in the five boys who continued to bleed. Factor VIII dosage was adjusted to achieve a trough level of > 1%; 4 responded to an increase in the dose of factor VIII; 1 had an adequate trough but, due to compliance issues, was taken to synovectomy. Serial clinical and radiographic assessments determined stabilization of joint disease in more than one-half of the boys. No child showed reversal of abnormal radiographic findings. Institution of aggressive factor VIII and IX concentrate in children with established hemophilic arthropathy does not reverse joint disease but may alter the clinical course of hemophilia. Future studies to compare this intervention with primary prophylaxis instituted prior to the onset of recurrent joint hemorrhage are warranted.

The effects of postponing prophylactic treatment on long-term outcome in patients with severe hemophilia

“…When to start prophylaxis is an important issue, because it has been shown that early prophylaxis can prevent joint damage 7 and late prophylaxis may decrease but does not stop further deterioration of damaged joints over a period of several years. 3,21 In the present study, prophylaxis only seemed to prevent arthropathy in most patients when started before the third joint bleed. The first question remains: Should we start prophylaxis before the first joint bleed?…”

Social participation of patients with hemophilia in the Netherlands

“…It has been shown that prophylaxis started later in life does not halt the progression of arthropathy. 18 The association between employment and HRQol should be interpreted with caution. Many factors may influence HRQol, such as viral infections and the presence of arthropathy.…”

Bioengineered Factor IX Molecules with Increased Catalytic Activity Improve the Therapeutic Index of Gene Therapy Vectors for Hemophilia B

“…Current standard treatment for hemophilias is based on replacement of the deficient factor with frequent intravenous injections of recombinant protein. This therapy has been shown to be effective in limiting acute bleeds and reducing mortality and morbidity (Manco-Johnson et al, 1994;Lofqvist et al, 1997). However, current replacement is unsatisfactory and presents several problems including complications in frequent venous access, product supply, inhibitor formation, allergic reactions, and thrombosis (Ragni, 2004).…”