Determining the Impact of Combination Oral Contraceptives on Von Willebrand Factor and Factor VIII in Healthy Patients and Patients With Von Willebrand Disease: A Scoping Review and Meta-Analysis.

Introduction: Von Willebrand disease (VWD) is a bleeding disorder characterized by a deficiency or dysfunction of Von Willebrand factor (VWF) and/or Factor VIII (FVIII), critical coagulation proteins. Individuals with VWD often use combination oral contraceptives (COCs) to manage heavy menstrual bleeding. However, the impact of COCs on VWF and FVIII levels and whether COC use affects VWD diagnosis is unclear.

Aim: To review the literature and assess the impact of COCs on FVIII and VWF.

Methods: This scoping review used the OVID platform in the MEDLINE, EMBASE and Cochrane databases. Keywords "combination oral contraceptives," "von Willebrand Factor," "Factor VIII" and "von Willebrand Disease" were searched. Primary studies exploring the impact of COCs on VWF and/or FVIII in patients of reproductive age were included. Article titles and abstracts were screened, followed by full-text reviews, data extraction and a meta-analysis.

Results: Twenty-seven studies were included. In healthy patients, 11 studies reported no change in VWF levels, while three found changes in VWF levels. Nine studies reported no change in FVIII levels, while 10 studies observed an increase. In patients with VWD, two studies found no significant change in VWF or FVIII levels. Meta-analysis revealed there was no significant difference in VWF% (Estimate: 2.62 (95%CI -0.5905, 5.831); p value: 0.4033) or FVIII% (Estimate: 2.99 (95%CI -4.85, 10.82); p value: 0.4552) with COC use.

Conclusion: The meta-analysis revealed no difference in VWD or FVIII levels between participants with and without COCs. The lack of observed differences suggests that COCs do not interfere with accurate VWD diagnosis.