Abstract Number: PB0473
Meeting: ISTH 2021 Congress
Background: Inhibitors are the most serious complication in patients with haemophilia A(HA) and B(HB). A complete understanding of inhibitor development is still lacking.
Aims: To update the clinical characteristics and the cumulative incidence of inhibitor development in the HEMFIL cohort study.
Methods: The HEMFIL is a Brazilian prospective cohort study on risk factors for inhibitor development. We include children with HA and HB before the first infusion of any factor concentrate and follow up until 75 exposure days (ED) or inhibitor development. Time to inhibitor development was calculated by Kaplan-Meier cumulative incidence with cumulative ED as the time variable.
Results: Previously, the Hemfil study reported a cumulative incidence of 36% [95%CI,26%-49%] for all inhibitors, 27% (95%CI,18%-40%) for high-titer and 13% (95%CI,6-24%) for low-titre inhibitors in a population of 70 included children under exclusive use of a third-generation recombinant FVIII [Advate®(Shire,USA)] (Jardim, et al 2018). Currently, 120 children were included, of whom 104 with HA and 16 with HB. A total of 10 patients with HB have completed 75ED and no patient developed inhibitor. Of all patients with HA, 89% are severe/moderately severe (FVIII:C<2%). Inhibitor was detected in 33/85 (38%) patients of which 22 (69%) were high-titre and 53/85 (62%) patients reached 75ED without inhibitors. Currently, the cumulative incidence of inhibitors in HA patients at 75ED is 35% (95%CI,26%-46%) for all inhibitors, 25% (95%CI,17%-36%) for high-titer and 13% (95%CI,8%-23) for low-titer inhibitors. The median time for inhibitor development remains 14ED (IQR,7-21) with a median age of 13 months (IQR,10-17). The median weight at inclusion is 9kg (IQR,8-12).
|Children with HA n = 104||Children with HA with no inhibitor
n = 53
|Children with HA
n = 32
|Age at baseline in months, median (IQR)||10 (6-17)||11 (7-17)||8 (4-12)|
|Family history of hemophilia, n (%)||56 (54)||27 (51)||18 (56)|
|Family history of Inhibitor, n (%)||3 (3)||1 (2)||1 (3)|
|More than 5 consecutive ED to FVIII**, n (%)||24 (23)||6 (11)||3 (9)|
|Skin color white, n (%)||62 (60)||37 (70)||17 (53)|
|Skin color Black, n (%||24 (23)||9 (17)||7 (22)|
|Skin color Mixed, n ( %)||17 (16)||6 (11)||8 (25)|
|High risk genetic mutation||53 (51)||20(38)||25 (78)|
|Low risk genetic mutation||45 (43)||28 (53)||6 (19)|
Conclusions: The cumulative incidence of inhibitor development under the exclusive use of a third-generation recombinant FVIII concentrate remains constant 3 years after the first report, inclusion of additional patients and a longer follow-up. This reinforces the robustness of these data.
To cite this abstract in AMA style:Jardim LL, Antônio Portugal Santana3 M, Gonçalves Chaves D, Werneck Zucheratto L, Hermida Cerqueira M, Santos Lorenzato C, Franco V, van der Bom J, Meireles Rezende S. Clinical Characteristics and Incidence of Inhibitors in Previously Untreated Children with Haemophilia: An Update of the Hemfil Cohort Study [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/clinical-characteristics-and-incidence-of-inhibitors-in-previously-untreated-children-with-haemophilia-an-update-of-the-hemfil-cohort-study/. Accessed November 28, 2023.
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