ABSTRACT
The increased prevalence of the laboratory diagnosis of von Willebrand disease (vWD)
in women presenting with menorrhagia has raised concerns regarding certain specifics
in vWD testing in women, including when vWD testing should be done in relation to
menses and whether testing should be done while the patient is not taking an oral
contraceptive (OC). These concerns have been based on historical reports that vWF
and factor (F) VIII:coagulant activity levels can decrease during menses and conceivably
increase the probability of diagnosing vWD when the patient is menstruating, whereas
hormone therapy can increase the vWF levels and conceivably mask the diagnosis of
vWD. Historically, the reports of a decrease in vWF levels during menstruation have
been in a relatively small total number of patients; this has not been confirmed in
two recent studies. In one study of 95 normal menstruating females sampled serially
at days 4 to 7, 11 to 15, and 21 to 28, there was no variation. In another study of
40 volunteers, by cross-sectional analysis there was no difference. However, interestingly
in that study, longitudinal analysis of samples showed a decrease in vWF antigen during
menstruation. In another recently published study, using cross-sectional analysis,
the lowest levels of vWF were found on days 1 through 4, whereas the highest were
identified on days 9 through 10. Conceivably, these groups were more finely divided
than were those in the other studies. In summary, in light of these conflicting results,
recommendations for testing exclusively during menses cannot be made. At this point,
it is not unreasonable to suggest that hematologists and gynecologists sample at least
once at the time of menstrual bleeding when the diagnosis of vWD in a menstruating
female is suspected. Consequently, sampling during the menstrual cycle may likely
capture the lowest levels of FVIIIC and vWF antigen. Regarding testing while the patient
is taking an OC, present preparations do not contain supraphysiological doses of estrogen
and are unlikely to affect the laboratory diagnosis of vWD. These studies primarily
have been in controls. Therefore, prospective studies in vWD women of menstrual variation
of the vWF levels and the impact of OCs on vWF levels are in order before specific
recommendations can be made regarding the timing of testing and whether patients should
be tested while the patient is not taking an OC. Other aspects regarding race, age,
preanalytical variables, and pregnancy potentially affecting the laboratory diagnosis
of vWD are also discussed in this review.
KEYWORDS
von Willebrand disease (vWD) - women - oral contraceptives - menorrhagia - menses
- von Willebrand factor (vWF)
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Peter A KouidesM.D.
Rochester General Hospital
1425 Portland Avenue, Rochester, NY 14621
Email: peter.kouides@viahealth.org
