Inhibitor development and mortality in non‐severe hemophilia A

Abstract

Summary. Background: The life expectancy of non-severe hemophilia A (HA) patients equals the life expectancy of the non-hemophilic population. However, data on the effect of inhibitor development on mortality and on hemophilia-related causes of death are scarce. The development of neutralizing factor VIII antibodies in non-severe HA patients may dramatically change their clinical outcome due to severe bleeding complications. Objectives: We assessed the association between the occurrence of inhibitors and mortality in patients with non-severe HA. Methods: In this retrospective cohort study, clinical data and vital status were collected for 2709 non-severe HA patients (107 with inhibitors) who were treated between 1980 and 2011 in 34 European and Australian centers. Mortality rates for patients with and without inhibitors were compared. Results: During 64 200 patient-years of follow-up, 148 patients died (mortality rate, 2.30 per 1000 person-years; 95% confidence interval (CI), 1.96-2.70) at a median age of 64 years (interquartile range [IQR], 49-76). In 62 patients (42%) the cause of death was hemophilia related. Sixteen inhibitor patients died at a median age of 71 years (IQR,. In ten patients the inhibitor was present at time of death; seven of them died of severe bleeding complications. The all-cause mortality rate in inhibitor patients was > 5 times increased compared with that for those without inhibitors (ageadjusted mortality rate ratio, 5.6). Conclusion: Inhibitor development in non-severe hemophilia is associated with increased mortality. High rates of hemophilia-related mortality in this study indicate that non-severe hemophilia is not mild at all and stress the importance of close follow-up for these patients.

Ischaemic events are rare, and the prevalence of hypertension is not high in Japanese adults with haemophilia: First multicentre study in Asia

“…Many of these patients may have needed to undergo surgery. Because older patients with a mild haemophilia phenotype are occasionally known to develop inhibitors after intensive substitution therapy at the time of the first invasive procedure, preliminary investigations, including mutation screenings, may be of importance…”

How I manage patients with inherited haemophilia A and B and factor inhibitors

“…It has also been shown that intensive treatment, for example in conjunction with surgery, will increase the risk, as has also been shown for severe haemophilia A (Gouw et al , ; van Velzen et al , ). The development of inhibitors in mild haemophilia A is a serious complication and it has been shown that the all‐cause mortality rate in inhibitor patients was >5 times increased compared with that for those without inhibitors (Eckhardt et al , ). Inhibitors in mild haemophilia may be different from the ones in severe haemophilia A and sometimes show so‐called type II kinetics similar to the autoimmune disorder acquired haemophilia (Luna‐Zaizar et al , ).…”

The changing face of immune tolerance induction in haemophilia A with the advent of emicizumab

“…Persons with haemophilia A who develop high‐titre inhibitors (HTI) become resistant to FVIII replacement therapy. This is associated with increased risk for bleeding and resultant morbidity (severe arthropathy and disability) and increased mortality . Studies have shown that haemophilia‐related long‐term morbidity and mortality as well as long‐term costs are diminished if inhibitors are eradicated …”