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Inhibitor development

Inhibitor development and risk factors

Inhibitor development is currently the most important complication of haemophilia treatment. Knowledge of risk factors can be used for the prediction of the risk of inhibitor development in patients with haemophilia

Samantha C Gouw MD PhD Amsterdam Hemophilia Treatment Center, Academic Medical Center, Amsterdam, The Netherlands Department of Paediatric Haematology, Emma Children’s hospital, Academic Medical Center, Amsterdam, The Netherlands

Patients with severe haemophilia typically suffer from joint and muscle bleedings either spontaneously or after minor trauma. The bleeding tendency can be effectively corrected by intravenous administration of factor VIII (FVIII) products. Today, the standard of care in patients with severe haemophilia is primary prophylaxis, regular infusions of FVIII aimed at making a normal life possible by preventing bleeds and haemophilic arthropathy.1


with adequate treatment, patients with severe haemophilia A have a life expectancy approaching that of the general population and a good health- related quality of life.2 However, during their lifetime, about 25% of patients with severe haemophilia A develop inhibitors that neutralise infused clotting factor.3

These polyclonal

high-affinity inhibitory IgG antibodies typically arise at the beginning of clotting factor therapy at a young age, at a median age of 15 months (interquartile range 10–22 months). In patients with severe haemophilia A, inhibitors develop after a

“Nowadays, with adequate treatment, patients with severe haemophilia A have a life expectancy approaching that of the general population”

median of 10 to 15 days of treatment with FVIII (exposure days).3

After 50 to 75

exposure days, the cumulative incidence of inhibitors reaches a plateau, after which the occurrence of inhibitors is infrequent, about 5 per 1000 patient- years.4

FVIII inhibitors may be either low-titer inhibitors, which may be transient and may be overcome by an increased dose of FVIII, or more serious

high-titer inhibitors, which preclude treatment with FVIII and require treatment with bypassing agents, such as activated prothrombin complex concentrate (Feiba®

activated factor VII (Novoseven®

) or recombinant ).

Patients with inhibitors have a higher morbidity because bleeding and surgery are more difficult to treat and primary prophylaxis with the deficient clotting


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