Mild hemophilia A

Abstract

Summary. Mild hemophilia A (HA), defined by clinical features and factor VIII coagulant activity (FVIII:C) between 0.05 and 0.40 IU mL−1, is characteristically distinct from severe HA. Indeed, although the molecular characterization of mild HA has permitted the identification of specific underlying mutations, its clinical phenotype is strikingly different from that of patients with a severe FVIII defect, where spontaneous hemorrhages or recurrent joint bleeding are usual manifestations. With aging, mild HA patients may develop complications (i.e. cancers and cardiovascular disorders), the management of which may prove challenging due to the concomitant bleeding tendency. Furthermore, the development of inhibitors provides an additional major complication in these patients, because it increases the severity of the bleeding phenotype and complicates their management. Standard management of mild HA includes the use of desmopressin and antifibrinolytic agents for minor bleeding episodes or surgical procedures, whilst major bleeding or surgery requires replacement therapy with FVIII concentrates. As regards treatment of patients with inhibitors, bypassing agents (i.e. activated prothrombin complex concentrates and recombinant activated FVII) have proven effective in the treatment of bleeding episodes, but as there are insufficient data to determine the optimal approach to immune tolerance induction in this group of patients, their optimal management remains controversial. Rituximab is a newer, promising therapeutic option for inhibitor eradication in such patients. Many aspects concerning mild HA remain to be clarified, including the molecular basis, the natural history and the optimal diagnostic and therapeutic strategies. Only large prospective studies will shed light on this condition.

Desmopressin response in hemophilia A patients with FVIII:C < 0.10 IU mL−1

“…As a result of this enrichment and due to small numbers, no effect of these F8 gene mutations on FVIII:C levels before and after desmopressin was found. Generally, a FVIII:C of ≥ 0.30 IU mL À1 is considered adequate for hemostasis in case of minor trauma or surgery [9,10]. Our data indicate that the majority of nonsevere hemophilia A patients with historically lowest FVIII:C levels < 0.10 IU mL À1 reaches this level at least up to 3 h after desmopressin infusion, but only a few have a sustained response after 6 h. It has previously been stated that a minimal FVIII:C level of 0.10 IU mL À1 is necessary to achieve FVIII:C levels of 0.30-0.50 IU mL À1 after desmopressin [4].…”

B6 and Bleeding: A Case Report of a Novel Vitamin Toxicity

“…Bleeding in mild hemophilia patients tends to be infrequent, and these patients rarely have spontaneous hemarthroses or develop arthropathy. 18,19 Patients with mild hemophilia generally only require intervention when bleeding develops because of trauma or a surgical procedure, in contrast to patients with severe hemophilia who have spontaneous joint bleeding and require lifelong factor VIII infusion for bleeding prophylaxis.…”

Inhibitor development in two patients with mild haemophilia A – spontaneous disappearance and no recurrence of the inhibitor after re-challenge

“…Th e mutation in patient 2 is located in the C1-domain, which is essential for the binding of FVIII to von Willebrand factor (vWF). Missense mutations within this domain may alter the core structure of FVIII and/or disrupt FVIII-vWF interaction [12]. In proximity to the mutation found in patient 2 missense mutations in codon 2090 and 2098 were described, resulting in defective vWF-binding and causing mild haemophilia A [13,14].…”