Diagnosis, laboratory aspects and management of acquired hemophilia A

Abstract

Acquired hemophilia A (AHA) is a rare autoimmune disease, characterized by severe, often life-threatening hemorrhages in patients without a prior history of bleeding disorder. It most frequently occurs in the elderly, and may be associated with other clinical conditions, such as cancer, autoimmune diseases, pregnancy or without a relevant cause. Diagnosis and correct therapy are crucial for the patient's outcome. Management of the disease consists of gaining immediate control of acute bleeding and the starting of an immunosuppressive therapy in order to eradicate the anti-factor VIII autoantibody. Factor VIII bypassing agents, such as prothrombin complex concentrates or recombinant activated factor VII, have proven effective in bleeding control, whereas the combined therapy of cyclophosphamide and corticosteroids seems to be, at present, the best immunosuppressive option. Other treatments including Rituximab, immunoadsorption or induction of immune tolerance are still experimental, and need to be validated through controlled clinical trials.

A patient with acquired hemophilia A induced by clopidogrel

“…FVIII autoantibodies occur in patients in the postpartum period and those with concomitant diseases or conditions (i.e., autoimmune disorders, malignancies, and drug abuse). However, up to 50% of cases develop without any relevant medical illness [3]. The mortality rate of AHA is as high as 16% [4].…”

Acquired haemophilia A initially diagnosed as angioedema

“…It affects elderly and postpartum women (20–40 years) with the incidence of approximately 1.5–1.3/million/year 2. Although uncommon, these autoantibodies are associated with a high rate of morbidity and mortality as severe bleeds occur in up to 90% of affected patients and the mortality rate is high, ranging from 8% to 22% 2 3.…”

“…It affects elderly and postpartum women (20–40 years) with the incidence of approximately 1.5–1.3/million/year 2. Although uncommon, these autoantibodies are associated with a high rate of morbidity and mortality as severe bleeds occur in up to 90% of affected patients and the mortality rate is high, ranging from 8% to 22% 2 3. About 50% of AH cases occur without underlying disease while the remaining cases may be associated with postpartum period, autoimmune diseases, underlying haematological or solid organ malignancy, infections, or use of medications 1 2.…”

“…Although uncommon, these autoantibodies are associated with a high rate of morbidity and mortality as severe bleeds occur in up to 90% of affected patients and the mortality rate is high, ranging from 8% to 22% 2 3. About 50% of AH cases occur without underlying disease while the remaining cases may be associated with postpartum period, autoimmune diseases, underlying haematological or solid organ malignancy, infections, or use of medications 1 2. Unlike congenital haemophilia, this condition results in gastrointestinal bleeding, retroperitoneal and other soft tissue haematomas 1 3.…”

Successful treatment of acquired hemophilia A, complicated by chronic GVHD, with tocilizumab

“…Acquired hemophilia A is a rare bleeding disorder characterized by the presence of autoantibodies which inhibit coagulation factor VIII (FVIII) [1][2][3]. Although the precise pathogenesis of this disease remains unknown, failure to activate regulatory T cells likely plays a crucial role in the development of FVIII inhibitors [4].…”