Acquired Haemophilia A: An Intriguing Disease

Abstract

Acquired Haemophilia A is a rare acquired bleeding disorder caused by autoantibodies directed against Factor VIII, which neutralize FVIII activity. These inhibitors differ from alloantibodies against FVIII which can occur in congenital Haemophilia A after repeated exposures to plasma-derived or recombinant FVIII products. In most cases the disease occurs suddenly in subjects without personal or familiar history of bleedings, with symptoms that may be mild, moderate or severe. However, only laboratory alterations are present in ̴ 30% of patients. The incidence varies from 1 to 4 cases per million/year; more than 80% of patients are elderly, males and females are similarly affected. There is a small peak of incidence related to pregnancy in young women aged 20–40 years. The disease may be underdiagnosed in the elderly. The diagnostic algorithm is based on an isolated prolonged activated partial thromboplastin time, normal thrombin time, absence of Lupus Anticoagulant and a mixing test that reveals the presence of an inhibitor: the finding of reduced FVIII activity and the detection of neutralising autoantibodies against FVIII lead to diagnosis. The disease is idiopathic in 44%-63% of cases, while in the others etiological factors are present. Bleeding prevention and treatment are based on therapeutic tools as bypassing agents, recombinant porcine FVIII concentrate or, in a limited number of cases, FVIII concentrates and desmopressin. As soon as the diagnosis has been made, immunosuppressive therapy must be started to eradicate the inhibitor. Better knowledge of the disease, optimal management of bleeding and eradication of the inhibitor have significantly reduced morbidity and mortality in most patients. 
 
 Keywords: autoantibodies against FVIII, bleeding symptoms, bleeding treatment, eradication therapy.

Innovative Therapies for Acquired Hemophilia A

“…21 Due to its undoubted advantages over traditional replacement therapy (i.e., the subcutaneous route of administration and the long half-life of 28 days), emicizumab has been investigated in other bleeding conditions characterized by FVIII deficiency, including severe von Willebrand disease and AHA. 23,24 The data available on the off-label use of emicizumab for AHA are limited, consisting mostly of case reports or retrospective case series. 25 In most reports, emicizumab was used as prophylaxis of recurrence after the control of bleeding with bypassing agents, while in some studies it was a second-line treatment of acute bleeding after failure of first-line approaches.…”

The Possible Non-Mutational Causes of FVIII Deficiency: Non-Coding RNAs and Acquired Hemophilia A

“…In most cases, the disease occurs suddenly in subjects without a personal or familiar history of bleeding, with symptoms that may be mild, moderate, or severe. AHA mostly affects female patients while HA is mainly caused by a mutation in F8 and affects male patients (37)(38)(39). The bleeding pattern of AHA is different from that of HA.…”

Acquired Hemophilia A: A Retrospective Multicenter Analysis of 42 Patients

“… 1 In AHA, bleeding occurs due to neutralization of the activity of FVIII by inhibitory antibodies. 2 – 4 Without proper treatment, fatal bleeding may occur, with mortality rate ranging from 9% to 41%. 5 Treatment is with hemostatic therapy to control acute bleeding and immunosuppressive therapy (IST) to eradicate FVIII inhibitory antibodies.…”