Aspects of the Laboratory Identification of von Willebrand Disease in Women

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.