Mild hemophilia A.
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.
Franchini
M
M
Servizio di Immunoematologia e Medicina Trasfusionale, Dipartimento di Patologia e Medicina di Laboratorio, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy. mfranchini@ao.pr.it
Favaloro
E J
EJ
Lippi
G
G
D000933:Antifibrinolytic Agents / Q000627:therapeutic use; D001323:Autoantibodies / Q000097:blood; D001777:Blood Coagulation / Q000235:genetics; D018450:Disease Progression; D005169:Factor VIII / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006467:Hemophilia A / Q000097:blood* / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy; D006470:Hemorrhage / Q000097:blood / Q000188:drug therapy / Q000209:etiology*; D006490:Hemostatics / Q000627:therapeutic use; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000933:Antifibrinolytic Agents; D001323:Autoantibodies; D006490:Hemostatics; D005169:Factor VIII