Bleeding severity in patients with rare bleeding disorders: real-life data from the RBiN study

Abstract

Patients with hereditary rare bleeding disorders (RBDs) present with diverse hemorrhagic symptoms. Correlation between factor activity levels and clinical bleeding severity is poor for most RBDs. Threshold factor activity levels have been previously described in relation to bleeding severity but have not yet been validated. The Rare Bleeding Disorders in the Netherlands (RBiN) study is a nationwide cross-sectional study of patients registered in all 6 Dutch Haemophilia Treatment Centers with a known RBD and who are age 1 to 99 years. Bleeding scores were determined, and laboratory and clinical data were extracted from patient files. In all, 263 patients were included, of whom 202 (77%) attended the scheduled study visit. The median International Society of Thrombosis and Haemostasis (ISTH) bleeding assessment tool (BAT) score was 9. Correlations between baseline factor activity levels and ISTH BAT scores were strong for deficiencies in factor II (FII) (r = –0.792) and FX (r = –0.838) and were moderate for deficiencies of fibrinogen (r = –0.683), FV (r = –0.623), FVII (r = –0.516), FXIII (r = –0.516), and α2-antiplasmin (r = –0.594). There was no correlation for FXI deficiency (r = –0.218). The RBD BAT identified more women (94% vs 83%) and children (100% vs 71%) with an RBD than the ISTH BAT did. Importantly, 48% of patients had more severe bleeding than predicted for their baseline factor activity level. In addition, 34% of patients were predicted to be asymptomatic, but they actually had grade 2 (31%) or 3 (3%) bleeding. Bleeding severity in patients with RBDs is more pronounced than previously anticipated. The previously determined threshold factor activity levels to ensure no (spontaneous) bleeding in patients with an RBD are inaccurate. This trial was registered at www.clinicaltrials.gov as #NCT03347591.

Effect of lower VWF and FXI levels on levonorgestrel IUS and endometrial ablation treatment success in heavy menstrual bleeding: An exploratory study

“…In-mostly mild-factor XI deficiency, this proportion was 55%. 2 Similar data have been reported in carriers of haemophilia. 3 A large proportion of women with HMB has an underlying bleeding disorder: A meta-analysis of 11 studies concluded that 13% of these women have VWD.…”

Major differences in clinical presentation, diagnosis and management of men and women with autosomal inherited bleeding disorders

“…The WiN study was performed between 2007 and 2009 and included 834 VWD patients [ 13 , 14 ]. The RBiN study was performed between 2017 and 2019 and included 263 patients with RBDs [15] . The TiN study was performed between 2016 and 2018 and included 62 patients with confirmed CPDs [16] .…”

“…At inclusion in the studies, patients filled in an extensive questionnaire containing questions on age of first bleeding and treatment, reason for referral, age of diagnosis and bleeding requiring hemostatic treatment in the year prior to inclusion in the study. Additionally, in the WiN study a self-administered Tosetto bleeding score (BS) was obtained, whereas in the RBiN and TIN studies the ISTH-BAT was obtained by the investigator [ 15 , 19 , 20 ]. We have previously shown that the self-administered BS obtained in the WiN study was comparable to the investigator obtained BS [14] .…”

“…We have previously shown that the self-administered BS obtained in the WiN study was comparable to the investigator obtained BS [14] . Lastly, blood samples were drawn to measure relevant coagulation factor levels in a central laboratory for each of the studies [ 13 , 15 , 18 , 21 , 22 ]. Laboratory measurements have been described in detail previously [ 13 – 16 ].…”

Treatment of patients with rare bleeding disorders in the Netherlands: Real‐life data from the RBiN study

“…4,5 A significantly higher prevalence is seen in populations with a high rate of consanguinity. 1,3,4 Patients with RBDs exhibit a wide variety of symptoms, ranging from asymptomatic or only minor bleeding to severe and lifethreatening bleeding. 6 In general, characteristic bleeding symptoms for all RBDs are mucosal tract bleeding episodes, such as epistaxis and menorrhagia, and excessive bleeding during and after invasive procedures and delivery.…”