Abstract Number: PB0982
Meeting: ISTH 2020 Congress
Theme: Hemophilia and Rare Bleeding Disorders » Hemophilia - Clinical
Background: It is increasingly recognized that carriers of hemophilia A (HA) and B (HB) can experience abnormal bleeding regardless of their factor VIII (FVIII) or IX (FIX) level. The CHiC Study is a large national study comprehensively examining abnormal bleeding symptoms in hemophilia carriers utilizing CBDR-R (the Canadian Bleeding Disorder Registry Research Module).
Aims: This study aims to better understand the pathophysiology of abnormal hemophilia carrier bleeding.
Methods: The Research Ethics Boards at Queen’s University and each participating centre granted clearance for this study. Adult hemophilia carriers from six bleeding centers across Canada were enrolled with informed consent. Questionnaires (Self-Administered Bleeding Assessment Tool, SF36v2) and hemophilia joint health scores (HJHS) were completed, and peripheral blood was collected. Assays including FVIII/IX one-stage (FVIII:OS/FIX:OS), FVIII chromogenic (FVIII:Ch), FVIII:Ag, and X Chromosome inactivation ratio (XIR) were performed in a centralized laboratory.
Results: Ninety-seven carriers are currently enrolled, and 79 blood samples have been received. Descriptive data is shown for carriers of hemophilia A (table 1) and B (table 2). In HA carriers, a weak correlation exists between bleeding score (BS) and FVIII:OS (r=-0.315, p=0.010), and FVIII:Ch (r=-0.285, p=0.020). FVIII:Ag correlates with FVIII:OS (r=0.731, p< 0.0001), FVIII:Ch (0.653,
p< 0.0001), and BS (-0.285, p=0.022). No correlation is present between XIR and FVIII:OS (r=-0.012, p=0.923), FVIII:Ch (r=-0.093, p=0.467), BS (r=-0.078, p=0.555) or HJHS (r=0.012, p=0.939). In HB carriers, a significant correlation exists between FIX:OS and HJHS (r=0.732, p=0.039), but not BS (r=-0.612, p=0.107). Overall, a moderate correlation exists between BS and the SF36v2 physical component summary (r=-0.400, p=0.002), and the SF36v2 mental component summary (r=-0.325, p=0.016).
Conclusions: Consistent with previous studies, there is a weak correlation between factor level and bleeding score in HA carriers. Enrolment for this study is ongoing with future plans for modelling to identify the relative contribution of additional determinants of bleeding.
| HA Carriers | Values | Max-Min | HA % Abnormal | Reference Values (Healthy) |
| Age (n=68) | 42 | 18-75 | n/a | n/a |
| Bleeding Score (n=80) | 7 | 0-28 | 65% | 0-5 |
| FVIII:OS (IU/mL) (n=70) | 0.52 | 0.20-1.72 | 49% | 0.5-1.50 |
| FVIII:Ch (IU/mL) (n=70) | 0.50 | 0.09-1.72 | 50% | 0.5-1.50 |
| FVIII:Ag (IU/mL) (n=67) | 0.51 | 0.15-2.07 | 45% | 0.5-1.50 |
| XIR (n=64) | 57:43 | 34:66-85:15 | 10% | 25:75-75:25 |
| HJHS (n=52) | 3 | 0-22 | 18% | 0-6 |
| SF36v2 PCS (n=56) | 53.16 | 29.37-67.69 | 2% | <30 |
| SF36v2 MCS (n=56) | 44.65 | 19.62-61.29 | 5% | <30 |
[Table 1: Descriptive statistics from Hemophilia A (HA) carriers in the CHIC study.]
| HB Carriers | Values | Max-Min | HB % Abnormal | Reference Values (Healthy) |
| Age (n=8) | 40 | 23-63 | n/a | n/a |
| Bleeding Score (n=10) | 7 | 2-22 | 60% | 0-5 |
| FIX:OS (IU/mL) (n=8) | 0.69 | 0.11-1.30 | 13% | 0.5-1.50 |
| XIR (n=9) | 64:36 | 13:87-78:22 | 22% | 25:75-75:25 |
| HJHS (n=9) | 2 | 0-16 | 22% | 0-6 |
| SF36v2 PCS (n=10) | 57.05 | 34.81-61.88 | 0% | <30 |
| SF36v2 MCS (n=10) | 45.18 | 19.62-57.13 | 20% | <30 |
[Table 2: Descriptive statistics from Hemophilia B (HB) carriers in the CHIC study.]
To cite this abstract in AMA style:
de Repentigny K, Hinds M, Grabell J, Keepanasseril A, Iorio A, Rydz N, Jackson S, Robinson S, Sun L, Belletrutti M, James P. The CHiC Study: The Canadian Hemophilia Carriers Study – Preliminary Results [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/the-chic-study-the-canadian-hemophilia-carriers-study-preliminary-results/. Accessed October 1, 2023.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/the-chic-study-the-canadian-hemophilia-carriers-study-preliminary-results/