Inapparent Von Willebrand Disease as the Underlying Cause of Menorrhagia Attributed to Uterine Fibroids.
Authors: Mohamed Tarek , Sycheva Tatyana , Schneider Douglas R. , Chokalingam Swati R. , Weinstein Robert 
Published: April 2020

Menorrhagia is a public health issue affecting 15% of American women, 300,000 of whom undergo hysterectomy each year. 50% of menorrhagia cases are not explained by gynecological disorders like uterine fibroids but in up to 1/3 of such cases bleeding disorders such as von Willebrand disease (vWd) may be present. No cases have been reported to indicate whether women with fibroids and menorrhagia should be investigated for vWd, particularly when screening tests (aPTT or bleeding time) are normal. We report herein 2 cases which demonstrate that inapparent vWd (normal screening tests) should indeed be sought in certain such cases of menorrhagia. Patient #1 was a 44 y/o African-American woman with severe menorrhagia since menarche, multiple 2 cm fibroids and severe iron deficiency anemia (Hgb 7.9 g/dl; MCV 68.5 FL; ferritin 1 ng/ml). Menstrual periods lasted 7 days. She bled through her clothes the first 1–3 days. Intolerant of oral iron, she required weekly injections of iron sucrose (100 mg) to keep up with menstrual losses. A sister in another state was also known to have menorrhagia. Patient #2 was a 40 year old Caucasian woman with severe menorrhagia since menarche (age 11 years), intramural fibroids and severe iron deficiency anemia (Hb 8.9 g/dl, MCV 64.9 FL, ferritin 4 ng/ml). Menstrual periods lasted 7 days, changing pad every hour for the first 2 days.. She bled through her clothes the first 2–3 days and was unable to keep up with menstrual losses using oral iron. Her younger sister also had menorrhagia.

Patient Screening Tests Timing fVIII(%) * vWf Ag (%) * Ristocetin co-factor (%) * vW multimer pattern Comment * reference range: 55–200 #1 PTT 31 sec, BT 6 min, Blood Group O+ Mid cycle 61 54 42 Unknown Normal multimer pattern obtained 30 minutes after pre-op injection of DDAVP and also 4 months post hysterectomy Menses 37 48 23 Type II post hysterectomy 53 52 50 Normal #2 PTT 31.5 sec, BT normal, Blood Group O+ Mid cycle 177 117 120 Normal DDAVP nasal spray shortened menstrual period from 7 days (72 pads) to 5 days(20 pads). Younger sister and nephew subsequently diagnosed with vWd. Menses 74 46 52 Type I

These cases illustrate that the assumption that severe menorrhagia is explained by simple anatomical abnormalities such as uterine fibroids may cause a significant hemostatic defect to be overlooked. Even normal screening tests, or vW tests obtained during follicular phase, do not rule out vWd in women with severe menorrhagia. The vW panel should be repeated at the start of menses. Patient #1 demonstrates a hitherto unknown association between uterine fibroids and acquired vWd which was apparently cured by hysterectomy and may suggest a mechanism by which fibroids cause menorrhagia. DDAVP controlled the menorrhagia of Patient #2 and may have done so in Patient #1 as well. Physicians should be alert to the possibility of inapparent vWd as the underlying cause of menorrhagia in women with uterine fibroids. High index of suspicion and careful diagnostic work up may provide an opportunity to avoid needless hysterectomy in some patients.