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. 2023 Apr;21(4):880-886.
doi: 10.1016/j.jtha.2022.11.045. Epub 2022 Dec 27.

Variability in International Society on Thrombosis and Haemostasis-Scientific and Standardization Committee endorsed Bleeding Assessment Tool (ISTH-BAT) score with normal aging in healthy females: contributory factors and clinical significance

Dearbhla Doherty  1 , Julie Grabell  2 , Pamela A Christopherson  3 , Robert R Montgomery  4 , Barry S Coller  5 , Michelle Lavin  6 , James S O'Donnell  7 , Paula D James  2 ; Zimmerman Program Investigators
Affiliations

Variability in International Society on Thrombosis and Haemostasis-Scientific and Standardization Committee endorsed Bleeding Assessment Tool (ISTH-BAT) score with normal aging in healthy females: contributory factors and clinical significance

Dearbhla Doherty et al. J Thromb Haemost. 2023 Apr.

Abstract

Background: Bleeding assessment tools are key screening tests used in the evaluation of patients with suspected inherited bleeding disorders. The International Society on Thrombosis and Haemostasis-Scientific and Standardization Committee endorsed Bleeding Assessment Tool (ISTH-BAT) has differing reference ranges for adult males (0-3), adult females (0-5), and children (0-2), reflecting differing bleeding symptoms and exposure to hemostatic challenges in these healthy population subgroups. Age is known to markedly impact bleeding score in individuals with von Willebrand disease. However, the influence of age on bleeding score in healthy adult controls is poorly understood.

Objectives: We aimed to assess variability in ISTH-BAT score with age among healthy control females.

Methods: We used the legacy "Merging Project" dataset of normal healthy controls upon which current ISTH-BAT normal ranges are based. We included women, totaling 646 individuals. The normal range (middle 95th percentile) of total ISTH-BAT and grouped subdomain scores between age quartiles was assessed.

Results: The normal range of ISTH-BAT scores increased with age, ranging from 0 to 4 in the youngest quartile (age range, 18-30) to 0 to 6 in the oldest (age range, 52-88). This increased variability with aging was related both to high menorrhagia domain scores in older women and an increase in postprocedural bleeding with accumulated exposure to hemostatic challenges.

Conclusions: Cumulatively, our data highlight that normal aging leads to increased variability in bleeding scores in healthy adult females. Further refinement of the ISTH-BAT with age-adjusted reference ranges may improve the sensitivity and specificity of the tool among females.

Keywords: blood coagulation disorders; decision support techniques; hemorrhage; inherited; menorrhagia; von Willebrand diseases.

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Conflict of interest statement

DECLARATION OF COMPETING INTERESTS

D.D. has received educational support funding from Amgen and Novo Norodisk. M.L. acts as a consultant for Sobi, Band Therapeutics and CSL Behring. M.L. has received speaker’s fees from CSL Behring and Pfizer and indirect funding for development of educational content from Takeda. J.S.O. has served on the speaker’s bureau for Baxter, Bayer, Novo Nordisk, Boehringer Ingelheim, Leo Pharma, Takeda, and Octapharma. He has also served on the advisory boards of Baxter, Bayer, Octapharma CSL Behring, Daiichi Sankyo, Boehringer Ingelheim, Takeda, and Pfizer. J.S.O. has also received research grant funding awards from Baxter, Bayer, Pfizer, Shire, Takeda, and Novo Nordisk. P.J. has research funding from Bayer, and acts as a consultant for Star/Vega Therapeutics and Band Therapeutics. The other authors have no relevant conflicts of interest to declare.

Figures

FIGURE 1
FIGURE 1
(A) ISTH-BAT score by age quartile among females (Quartile 1-Quartile 4), with each point representing the total ISTH-BAT score of a healthy control individual. Distribution of ISTH-BAT scores changed with normal aging; subjects in the oldest quartile (Q4) were approximately 3 times more likely to have an ISTH-BAT score of ≥4, when compared with those in the youngest quartile (Q1), (Q4 vs Q1; 13.77% vs 4.88%; odds ratio, 3.12; 95% CI, 1.40–6.74). (B) Heat-map visualization illustrating total ISTH-BAT and sub group domain scores (rows) reported by each subject (columns) in the youngest (Q1) and oldest quartile (Q4). Increasing scores are illustrated by color change, from green (score of 0) to red (score of 6), as shown in color key. Individuals in both quartiles had similar distribution of Spontaneous domains scores. In contrast, the distribution of sex-specific domains scores (sum of the Menorrhagia and PPH domains) and challenge domains scores (sum of the Surgery and Dental Extraction domains) broadened with age. Only subjects with ISTH-BAT ≥1 are included for illustrative purposes. ISTH-BAT, International Society on Thrombosis and Haemostasis-Scientific and Standardization Committee endorsed Bleeding Assessment Tool; PPH, postpartum hemorrhage
FIGURE 2
FIGURE 2
Illustrative representation of variability in ISTH-BAT score with normal aging, Increasing scores are illustrated by color change, from green (score of 0) to red (score of 6), as shown in color key. HMB, heavy menstrual bleeding; ISTH-BAT, International Society on Thrombosis and Haemostasis-Scientific and Standardization Committee endorsed Bleeding Assessment Tool
See this image and copyright information in PMC

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