Acquired Haemophilia A: An Intriguing Disease

Abstract

. Acquired Haemophilia A is a rare acquired bleeding disorder caused by Factor VIII autoantibodies, which neutralise 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 a 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 the 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 by-passing 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.

Figure 1

Legend. aPTT = activated partial thromboplastin time; DIC = disseminated intravascular coagulation; DTI = direct thrombin inhibitor; FVIII = factor VIII; FIX = factor IX; FXI = factor XI; FXII = factor XII; PT = prothrombin time; ratio = test plasma time/normal reference plasma time; TCT=thrombin clotting time.