Prevalence of Acute and Chronic Migraine Among Patients with Von Willebrand Disease

Background: The prevalence of migraine in the general population is approximately 18% in females and 6% in males (Lipton, et. al. Headache 2001;41:646). Among migraineurs, 7-8% experience chronic migraines (CM) (Adams AM, et. al. Cephalalgia 2015;35:563). Von Willebrand factor (VWF), secreted from endothelial cells, is reported to be elevated in migraineurs and in particular during the course of migraine, although its role is unclear (Cesar, et. al. Acta Neurol Scand 1995;91:412; Tietjen, et. al. Neurology 2001;57:334; Tietjen, et. al. Cephalalgia 2018;38:511). Patients with Von Willebrand Disease (VWD) have low levels of or a defective form of VWF, which has led some to hypothesize a lower prevalence of migraine in the VWD population. Conversely, a retrospective case control study found that migraine in VWD patients (n=197) was 6 times more prevalent when compared with age- and sex-match healthy controls (n=197) (18% vs. 3%, respectively)(Hassan, et. al. Intl Journal of Hem, Blood Diseases and Disorders 2014;2:23-5). The current investigation was performed to further explore the relationship between migraine and VWD. Methods: A cross-sectional study was conducted in March 2021 using the InCrowd digital survey tool in which patients with self-reported diagnosis of VWD were invited to participate. The study included 75 VWD patients ≥18 years of age. Survey questions detailed VWD sub-type, gender, clinical diagnosis of migraine, medical specialty diagnosing migraine, migraine treatments, and age of diagnosis. The Lipton Identify Chronic Migraine (ID-CM) tool was used within the survey to identify patients who had experienced chronic migraine(Lipton, et al. Cephalalgia. 2016;36:203). Criteria for designation of chronic migraine from the ID-CM was either the combination of Frequency of Migraine and Symptoms or the combination of Use of Medication and Activity Avoidance. Results: The gender distribution of the 75 participants was 83% female and 17% male. The sub-type of VWD diagnosed was: Type 1 (57%), Type 2 (28%), Type 3 (15%). Fifty-seven percent (57%) of all VWD patients reported being diagnosed with migraine. Rates did not vary significantly by VWD sub-type. Diagnosed migraine was only slightly more common in females (60%, n=62) compared with males (46%, n=7). Average age of diagnosis was 22 years with a median of 17 years (n=43). Two clear clusters defined the age of diagnosis with migraine. The first was between ages 10 and 20 (n=24, 56% of total sample reporting age) and the second was approximately age 30 [28-32] (n=8, 19% of total sample reporting age). Migraine diagnosis was established by primary care physicians (44%), neurologists (44%) hematologists (9%), and headache specialists (2%). Only 4% of surveyed patients met the ID-CM criteria for chronic migraine, yet 71% of patients met the criteria for migraine symptoms. Chronic migraine diagnosis using the ID-CM tool requires a combination of headache frequency (at least half of the past 30 or 90 days), multiple migraine symptoms (present >rarely in the past 30 days), medication use for headache as well as interference with activities (≥10 of the past 30 days) and a headache that either interfered with plans or caused worry for making plans (>rarely in the past 30 days). Frequency of migraine was mentioned by 11% of patients and symptoms by 71%, medication use by 31%, activity limitation by 15%, and changing plans by 25%. Conclusions: This survey illustrates that migraine is significantly more common in people with VWD than in the general population, regardless of VWD sub-type. However, the age-associated incidence pattern follows a similar bimodal distribution as observed in the general population(Victor, et al. Cephalalgia. 2010;30:1065). Notably, the prevalence of diagnosed migraine in VWD males approaches the prevalence in VWD females and exceeds that of females in the general population (Lipton RB, et. al. Headache 2001;41:646). These results suggest a distinct etiology of VWD that makes affected patients more susceptible to migraine. Notably, migraine treatment options may be more limited for these patients, given that traditional NSAIDs are commonly used for fast-acting migraine relief, but their antiplatelet effects and potential for gastrointestinal bleeding make them undesirable in VWD. Further investigation of both the etiology and treatment for VWD migraine is warranted.