Von Willebrand Disease as a Cause of Abnormal Uterine Bleeding

Introduction

Menorrhagia, i.e., abnormally heavy prolonged menstrual bleeding lasting more than 7 days, is a common complaint among women of reproductive age. The etiology of menorrhagia can be both local and systemic, but a specific cause is identified in less than 50% of cases. Although menorrhagia is a very common symptom of von Willebrand disease and other hereditary coagulation disorders, its significance as a predictor of mild bleeding disorders has only been seriously studied since the late 1990s.

Type 1 vWD, present in 70% of cases, is generally mild and only becomes problematic in haemostatically demanding situations such as menstruation or childbirth. Therefore, screening women with menorrhagia would be an ideal way to identify the presence of this disease. However, diagnosing vWD, especially its mild form, is challenging and complex, relying on a combination of clinical features and laboratory tests for von Willebrand factor antigen (vWF:Ag), von Willebrand factor functional activity (vWF:RCo), or factor VIII activity. The levels of these coagulation factors in plasma are influenced by many factors such as age, race, or blood type, and also fluctuate within the phases of the menstrual cycle. The prevalence of vWD in the general population is around 1%, but the prevalence among women with menorrhagia is much higher.

Reviewed Studies

The authors of the cited systematic review evaluated 11 studies that dealt with the prevalence of vWD in women with menorrhagia. The total number of patients in the studies was 988, and vWD was diagnosed in 131 of them. The prevalence across studies ranged from 5 to 24%, and although these figures were not consistent, they were still higher than in the general population. von Willebrand factor assessment was used to establish the diagnosis.

Discussion

In all studies, the prevalence of vWD in women with menorrhagia was higher than in the general population, although the exact values varied. This could have been due to the different conduct of each study or the selection of participants. Some studies involved women who self-diagnosed menorrhagia, while others selected them based on medical databases or gynecological clinics. The prevalence of vWD was lowest in the group of women with self-diagnosed menorrhagia, suggesting that they may not have had menorrhagia if subjected to objective testing.

Another important factor influencing prevalence is ethnicity. Studies from North America included a large proportion of Black women. Black women tend to have higher levels of vWF antigen, and von Willebrand disease is less common among them compared to white women.

The third important factor is blood group. Blood group 0 has been associated with lower levels of vWF:Ag and vWF:Ac. However, other studies suggest that blood type may not be as relevant as previously thought.

Diagnosis

Diagnosing von Willebrand disease is complex, and diagnosing its particularly mild form can be challenging. Laboratory diagnostics and classification of vWD include screening and diagnostic and differential tests. Typically, these involve testing for factor VIII levels, vWF antigen, and assessing vWF's ability to bind platelets (vWF:RCo). In addition to the von Willebrand disease panel, the following parameters should at least be determined for abnormal uterine bleeding: hCG, complete blood count with platelet count and differential white blood cell count, ferritin level, prothrombin time, activated partial thromboplastin time, and fibrinogen level. It is also advisable to exclude infection and thyroid dysfunction.

Conclusion

Von Willebrand disease is a cause of menorrhagia in a small but significant portion of women. The diagnosis of menorrhagia, white race, absence of pelvic pathology, and other bleeding manifestations on the body, especially in women before surgical procedures, should lead us to test for the presence of this disease.

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Sources:
1. Shankar M., Lee C. A., Sabin C. A. et al. Von Willebrand disease in women with menorrhagia: a systematic review. BJOG 2004; 111 (7): 734−740, doi: 10.1111/j.1471-0528.2004.00176.x.
2. Elmaoğulları S., Aycan Z. Abnormal uterine bleeding in adolescents. J Clin Res Pediatr Endocrinol 2018; 10 (3): 191−197, doi: 10.4274/jcrpe.0014.