The natural history of mild haemophilia: a 30‐year single centre experience

Abstract

Although up to 50% of all haemophilic patients followed at haemophilia treatment centres (HTCs) are affected by a mild factor VIII (FVIII) or factor IX (FIX) defect, published data regarding the natural history of these disorders are scarce. To fill this lack of information, a retrospective single centre study was conducted. All cases with mild haemophilia (75 A and 7 B) followed at the regional reference HTC of Parma were evaluated. The patients' median age at diagnosis was 11.5 years and their median age at first bleeding was 5.5 years; 95% of patients had a history of haemorrhagic problems during their life. Twenty-three percent of patients were infected by HCV, and none by HIV. Genetic analysis was performed in 80 patients (97% haemophilia A and 100% haemophilia B) and 21 different mutations were characterized. Eleven percent of patients had never received treatment, whereas 67% were treated with plasma-derived or recombinant FVIII/FIX concentrates (4% developed inhibitors). desmopressin (DDAVP) was used in 80% of the haemophilia A patients. The response to DDAVP was closely related to the patients' genetic profile, as 60% of non-responders had a mutation in the F8 promoter region. Patients with mild haemophilia may experience a variety of medical problems, sometimes challenging for the physicians, during their lifetime. The HTCs play an important role in the management of these patients, whose diagnosis is often delayed. The HTCs should improve patients' knowledge and consideration of their disease and encourage them to maintain regular contact with their haemophilia care provider.

Molecular and clinical predictors of inhibitor risk and its prevention and treatment in mild hemophilia A

“…Although FVIII increase occurs in most cases, only 50% to 60% of patients achieve FVIII levels higher than 50 U/dL. 3,[23][24][25][26] The peak postdesmopressin depends in part on the patient's basal FVIII level 24,25 and age. Young children often have markedly lower responses to desmopressin than adults, but they may become responsive at an older age.…”

“…Until recently, the disorder has received relatively little attention because of its purported low morbidity rate, resulting in an apparently uncomplicated quality and duration of life in the absence of virally induced comorbidities. [1][2][3] In a recent cohort study, 23% of patients with mild hemophilia were positive for hepatitis C virus, a proportion substantially lower than in patients with severe hemophilia. 3,4 In patients with mild hemophilia A (MHA), excessive bleeding usually occurs after minor trauma, dental procedures, or surgery.…”

“…[1][2][3] In a recent cohort study, 23% of patients with mild hemophilia were positive for hepatitis C virus, a proportion substantially lower than in patients with severe hemophilia. 3,4 In patients with mild hemophilia A (MHA), excessive bleeding usually occurs after minor trauma, dental procedures, or surgery. This is unlike patients with severe deficiency (FVIII , 1 U/dL), who frequently bleed spontaneously without preceding trauma.…”

“…2 Diagnosis of MHA usually occurs later in life, and a significant proportion of cases may be diagnosed during subsequent family investigation. 3,5 However, because of the delayed presentation of bleeding, sometimes these patients could be first seen by physicians who are not used to interpreting symptoms of bleeding. 6 Thus, these symptoms could be more dramatic at a time of initial assessment, with the risk for intensive treatment with FVIII concentrates potentially increasing the risk for inhibitor development.…”

“…3,4 Inhibitor development risk in MHA: not so early, not so low Some patients with MHA may develop inhibitory antibodies after treatment with FVIII concentrates, with a prevalence of 5% to 10%. 5,7,8 When exposure days (ED) are taken into account, the risk for inhibitor development clearly increases with the number of ED to exogenous, therapeutic FVIII concentrates.…”