Etiology of inhibitor development in hemophilia

Hemophilia A (Factor VIII deficiency) is a rare bleeding disorder that is treated by intravenous administration of clotting factor concentrates. A major challenge in the treatment is the development of inhibiting antibodies (inhibitors), directed towards F VIII. Inhibitors block the action of F VIII and thereby increase morbidity and mortality.

This research line aims to identify clinical and genetic risk factors for inhibitor development, especially in mild/moderate hemophilia.

* The INSIGHT study is an international cohort study performed in 34 Hemophilia Treatment Centers in 11 countries that has included 2700 moderate and mild hemophilia A patients. Genetic and clinical risk factors for inhibitor development will be identified in this cohort.
* Treatment of inhibitors in moderate and mild hemophilia is investigated in the TRIM study.
* DDAVP can be used as a treatment for bleedings circumventing the use of clotting factor concentrates, thereby reducing the risk of inhibitor development. The RISE study identifies predictors of DDAVP response in mild hemophilia A patients.
* Small changes in immunological responses may identify patients that will develop an inhibitor in an early stage. The PUPS study aims to analyze the immunological response in young children after their first exposures to F VIII concentrate.

Cerebral infarction and vaso-occlusion in Sickle Cell Disease

Sickle Cell Disease is a hereditary anemia caused by a mutation in the beta-globulin gene, that occurs predominantly in persons with African ancestry. Hallmarks of the disease are chronic haemolytic anemia and vascular occlusion, that may cause irreversible damage to all vital organs.

This research line aims to identify risk factors for “silent” cerebral infarction and to identify and treat its neuropsychological sequelae. We also study the pathophysiological processes of (painfull) vaso-occlusive crises and interventions to prevent these.
• FIND study: Finding Indicators of Neurological Damage is a multicenter observational cohort study that aims to identify genetic and clinical risk factors for “silent” cerebral infarction
• KLIK study: Quality of Life in Clinical Practice identifies (neuropsychological) problems in children with Sickle Cell Disease. By early identification therapeutic measures can be initiated as early as possible
• STAR is a multicenter observational study aiming to unravel allo-antibody formation in patients with Sickle Cell Disease
Effective start/end date01/12/2011 → …

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