Prevalence of FXI gene mutations in women with menorrhagia.

Menorrhagia is a common problem among women in the reproductive age.
Menorrhagia or heavy menstrual bleeding is objectively defined as greater than
or equal to 80 ml blood loss per menstrual cycle.3 At least 5 -10% of women in
reproductive age will seek medical attention for menorrhagia.4 The World Health
Organization estimates that 18 million women worldwide are affected.5
Menorrhagia is a common cause of iron deficiency anemia3;6 and may affect a
woman*s quality of life, her study or work and family and social interactions.7
Menorrhagia can be caused by a wide range of disorders.8;9
We performed an observational study about the prevalence of underlying bleeding
disorders in women with menorrhagia (METc 2009/217). Preliminary results of 91
women and 30 healthy volunteers showed that women with menorrhagia had
significantly lower levels of factor XI (FXI) compared to controls (100 vs 125
IU/dL; p=0.000). Of all the patients four had a lower FXI level (<70%). FXI is
a coagulation protein essential to normal haemostasis and acts by cleaving
coagulation factor IX. FXI deficiency, also known as haemophilia C, is an
autosomal bleeding disorder characterized by reduced levels of FXI in plasma
with a high prevalence (about 9%) in the Ashkenazi Jewish population.10 Women
with low levels FXI (<70%) are prone to excessive bleeding during menstruation.
Bleeding manifestations are not well correlated with the plasma levels of FXI
activity and bleeding episodes can vary widely among patients with similar FXI
levels.10;11 Recent studies suggested that the incidence of mild FXI deficiency
in Caucasians may be higher than expected.1;2 The factor XI (FXI) gene is
located on the long arm of chromosome 4 (4q35) with 23 kb in length and
consists of 15 exons and 14 introns. Until now, more than 90 FXI gene
mutations, associated with a FXI deficiency have been reported. Most of these
mutations are found in the Jewish population. To our knowledge, the prevalence
of FXI gene mutations in women with menorrhagia have not been reported.
However, the presence of mutations in FXI gene in women with menorrhagia could
probably lead to lower levels of FXI.
We want to perform an explorative study out of our previous study to
investigate the prevalence of FXI gene mutations in women with menorrhagia and
a control group of healthy female volunteers matched by age with normal
menstrual blood loss without hormonal treatment.

to investigate the presence and frequency of FXI gene mutations in patients
with menorrhagia and healthy volunteers.

Explorative study to investigate the prevalence and frequency of FXI gene
mutations in patients with menorrhagia and healthy volunteers from our previous
study.

Burden and risks: 20 mL blood will be taken from the patients and the controls
by venapunction. There are no benefits for the patients and the controls.