Mild Factor XI Deficiency in Women with Hypermenorrhea or Prolonged Postoperative Bleeding: A Genotype–Phenotype Analysis

Introduction Mild or subclinical Factor 11 (F11) deficiency can manifest primarily through gynaecological or postoperative (inluding caesarian section) bleeding symptoms, often in women with otherwise normal coagulation profiles. Identifying such cases is critical to improving diagnosis and counselling, especially when standard laboratory results underestimate clinical bleeding risk. Method Clinical, laboratory, and genetic data from 123 patients from 3 centres carrying F11 variants were retrospectively analyzed. F11 activity, bleeding scores (ISTH-Bleeding Assessment Tool, ISTH-BAT), and reported bleeding symptoms—including hypermenorrhoea, hematomas, and postoperative bleeding—were evaluated. Statistical analyses included descriptive statistics and correlation testing. FXI was measured by FXI deficient plasma (BCS, Siemens, Erlangen, Germany), genetic testing with NGS (NextSeq, Ilumina, San Diego, USA) Results Among 97 female participants, n=25 (26%) reported hypermenorrhea, and n=48 (49%) of individuals with≥1 surgery or birth experienced prolonged postsurgical . The mean F11 activity across the cohort was 40±17%, with no significant correlation between F11 activity and bleeding severity (r=0.04; p=0.65). Women with hypermenorrhea had significantly higher ISTH-BAT scores (mean 3.8±1.9) than those without (mean 1.5±1.6; pT, and c.1247G>A—were associated with moderate F11 activity (25–40%), but disproportionately high bleeding scores (ISTH-BAT 4–5). Strong intercorrelations were observed between hypermenorrhea, mucosal bleeding, and haematomas (r=0.6–0.9), defining a coherent mild bleeding phenotype in women with F11 variants. Fig. 1 FXI activity vs ISTH-BAT. Overall correlation r=0.12, p=0.28 : no significant association between FXI activity and bleeding severity. Points are marked by hypermenorrhea status (circles=no; squares=yes). Fig. 2 ISTH BAT by hypermenorrhea status. No hypermenorrhea: n =64, mean= 1.91±1.84; Hypermenorrhea: n =25, mean= 3.40±1.73. Welch t-test p=0.001 : significantly higher bleeding scores in women with hypermenorrhea Conclusion Mild F11 defects—especially heterozygous F11 variants with moderate activity reduction—are frequent among women presenting with hypermenorrhea or delayed postsurgical bleeding, despite near-normal laboratory results. These findings underscore the importance of detailed bleeding history and genetic testing in women with unexplained mucocutaneous or gynaecologic bleeding to detect qualitative F11 abnormalities and guide individualized hemostatic management [ 1 ] [ 2 ] [ 3 ] [ 4 ]. Publication History Article published online: 17 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany