Risk Factors for Inhibitor Development in Persons with Non-Severe Hemophilia A Open Access

Kempton, Christine (2008)

Permanent URL: https://etd.library.emory.edu/concern/etds/nc580m84s?locale=en
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Abstract

ABSTRACT

Hemophilia A, or factor VIII (FVIII) deficiency, is a congenital bleeding disorder
affecting 1/10,000 males. A significant complication of hemophilia A is the formation of
antibodies that bind FVIII at the time of treatment and inhibit FVIII activity. These
antibodies are termed inhibitors. One-quarter of new inhibitors occur in those with non-
severe (FVIII 1-40%) disease. In non-severe hemophilia A, intensive treatment with
FVIII has been observed in case series to precede inhibitor formation in a majority of
patients.
To estimate the risk of inhibitor formation following intensive exposure to FVIII,
defined as 6 or more consecutive days of FVIII, a case control study was performed.
Cases were defined as having had an inhibitor titer >1 BU/ml on two occasions.
Information on subject characteristics and treatments during the year prior to inhibitor
development or enrollment was retrospectively gathered. A blood sample was obtained
for FVIII genotyping.
Approximately 55% of case subjects had received intensive FVIII exposure,
during the year prior to inhibitor formation compared to 25.5% of controls during the
year prior to enrollment [unadjusted OR 4.55 (95% CI 1.78-11.60)]. In subjects 30 years
of age or older, intensive exposure had a greater association with inhibitor formation than
in those that were less than 30 years of age (OR 13.65 and 1.73 respectively). After
adjusting for a baseline FVIII of 1-2%, the odds ratio measuring the association between
intensive exposure to FVIII and inhibitor development was increased to 5.61 consistent
with a confounding effect. On multivariate analysis, intensive exposure to FVIII and a
baseline FVIII of 1-2% were associated with inhibitor formation after adjusting for age
<30 years, race, recombinant product use, and having less than 50 lifetime FVIII
exposure days. None of the subject or treatment characteristics were clearly associated
with inhibitor formation on subset analysis, although surgery as the indication for
intensive exposure as well as receiving FVIII by continuous infusion both showed a trend
toward an association.
This study confirms that intensive exposure is a strong risk factor for inhibitor
formation in non-severe hemophilia A. This association was present after adjustment for
the number of prior exposure days to FVIII and severity of disease and was stronger in
those over thirty years of age.

Table of Contents


TABLE OF CONTENTS



INTRODUCTION................................................ 1


BACKGROUND...................................................
2


METHODS.........................................................
7


RESULTS..........................................................11


DISCUSSION.....................................................15


REFERENCES.................................................... 17


TABLES AND FIGURES........................................
20





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