Break-through bleeding in relation to predicted factor VIII levels in patients receiving prophylactic treatment for severe hemophilia A.
BACKGROUND
The role of prophylactic factor VIII (FVIII) to decrease hemophilic bleeding and arthropathy is well established. The rationale for this strategy is to convert patients with severe hemophilia A to a moderate clinical phenotype by reducing time spent with a FVIII level <1 IU dL(-1). Studies to date, however, have not demonstrated a strong link between FVIII level and the bleeding rate.


OBJECTIVE
To assess the effect of FVIII level on break-through bleeding in patients with severe hemophilia A on prophylaxis.


METHODS
This study analysed data from 44 patients aged 1-6 and 99 patients aged 10-65 years with severe hemophilia A (FVIII <1 IU dL(-1)) who were treated with prophylactic FVIII as part of clinical studies assessing pharmacokinetics, safety and efficacy of a recombinant FVIII (Advate). Each patient had pharmacokinetic measurements and FVIII infusions recorded, and these were used to calculate time spent with a FVIII below 1, 2 and 5 IU dL(-1).


RESULTS
The data demonstrate that increasing time with a FVIII below 1 IU dL(-1) is associated with increased total bleeds and hemarthroses. Lack of adherence to the intended frequency of FVIII infusion was the most important determinant of low FVIII and increased bleeding. In children aged 1-6 years, the rate of bleeding was also influenced by FVIII half-life and clearance.


CONCLUSIONS
These data have important implications for the management of patients with severe hemophilia.
Collins
P W
PW
Arthur Bloom Haemophilia Centre, Department of Haematology, Medical School of Cardiff University, University Hospital of Wales, Heath Park, Cardiff, UK. peter.collins@cardiffandvale.wales.nhs.uk
Blanchette
V S
VS
Fischer
K
K
Björkman
S
S
Oh
M
M
Fritsch
S
S
Schroth
P
P
Spotts
G
G
Astermark
J
J
Ewenstein
B
B
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005169:Factor VIII / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics; D006467:Hemophilia A / Q000150:complications* / Q000188:drug therapy; D006470:Hemorrhage / Q000209:etiology*; D006801:Humans; D007223:Infant; D008875:Middle Aged; D010599:Pharmacokinetics; D011292:Premedication; D055815:Young Adult
C078147:F8 protein, human; D005169:Factor VIII