Abstract Number: PB1013
Meeting: ISTH 2020 Congress
Background: Several studies have investigated the intricate pathophysiological mechanisms leading to the development of FVIII inhibitors in hemophilia A patients. However, the etiology of their onset is very complex and is not yet fully understood. The inhibitors arise from a multicausal immune response involving both genetic (unmodifiable) and environmental (potentially modifiable) risk factors.
Aims: To address the need for a holistic approach to provide advanced risk management.
Methods: Report the current knowledge of genetic and environmental risk factors on inhibitor development.
Results: Two well-established unmodifiable risk factors are family history of inhibitors and the causative mutation’s nature (type of genetic variant affecting the F8).
Polymorphisms in immunomodulatory genes have also been found to play a role in differentiating individual response.
Although the mechanisms accounting for ethnicity differences remain somewhat unclear, it is well known that patients of African or Hispanic ancestry have an increased predisposition to develop inhibitors.
As for environmental factors, inhibitor development is surely affected by the source and type of the FVIII product and as well by treatment intensity.
Severe bleeds, surgery or concomitant infections have also been implicated in the context of concurrent immunological danger signals that up-regulate the immunologic reaction against exogenous FVIII.
Conclusions: Overall, inhibitor development is a phenomenon of multifactorial inheritance described by the liability/threshold model. Such an elaborate net of genetic and environmental interactions made it extremely difficult to create a clinical score system to quantify the individual risk.
Nowadays new large-scale hypothesis-generating approaches can provide the tools to study the personal specific array of multiple risk factors concurrently and identify the unique risk profile of each patient. Moreover these innovative technologies may allow timely reassessing the risk when a transient factor comes along.
From these revolutionary resources will be rising the opportunity to evolve new preventive approaches and develop novel therapeutic strategies.
To cite this abstract in AMA style:Duraes A. Inhibitor Development in Hemophilia A – Refining the Risk Assessment [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/inhibitor-development-in-hemophilia-a-refining-the-risk-assessment/. Accessed March 4, 2024.
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