Clotting Factor Concentration During Menstrual Phases in Women With and Without Heavy Menstrual Bleeding: A Systematic Review and Meta-Analysis

BACKGROUND: Cyclic sex-hormone fluctuation impacts clotting factor concentrations, being lowest during the follicular phase of the menstrual cycle. This pattern is unexplored in women with heavy menstrual bleeding (HMB), but potentially affects the timely diagnosis of underlying bleeding disorders.

AIM: Comparing clotting factor fluctuation in the follicular versus luteal phase, between women with and without HMB.

METHODS: A PubMed/MEDLINE systematic review on HMB and clotting factors. Articles reporting clotting factor concentrations in premenopausal women with and without HMB were included, categorized by follicular or luteal phase if the sampling moment was specified. A meta-analysis was performed and the effect of HMB on (cyclic) clotting factor concentrations was assessed.

RESULTS: A total of 21 out of 2158 articles were included. Clotting factors II, V, VII-XI, fibrinogen and von Willebrand factor (VWF) during the follicular and luteal phases were reported in women with HMB. All measurements in women with HMB were performed during the follicular or unspecified phase, hindering phase-specific assessment. Irrespective of phase, pooled measurements in women with HMB suggested elevated FVIII (pooled difference 21.8 IU/dL, 95% CI: 4.5-39.1, p = 0.01) and FV concentrations (pooled difference 15.8 IU/dL, 95% CI: 6.0-25.5, p = 0.002), but not VWF activity (pooled difference -11.0 IU/dL, 95% CI: -27.9 to 5.9, p = 0.20), compared to women without HMB.

CONCLUSION: Based on meta-analysis of limited data, women with HMB tend to exhibit slightly higher FVIII and FV concentrations as compared to those without. More research is needed in the follicular phase of women with HMB to assess the effect of menstrual phases on HMB.