Acquired Haemophilia A in the Elderly: Case Reports

Abstract

Acquired hemophilia A (AHA) is a very rare disease, caused by the development of autoantibodies, directed against circulating factor VIII of coagulation. Age distribution is bimodal, with a first peak occurring among young women in the postpartum period, and a second major peak of incidence among elderly patients in whom it is frequently associated with malignancy and drugs. This disease often represents a life-threatening bleeding condition, especially in the elderly, thus requiring a prompt therapeutic intervention, including control of acute bleeding and eradication of the inhibitor by immunosuppressive therapy. The diagnosis of AHA should be considered in any elderly patient who presents with bleeding and prolonged activated Partial Thromboplastin Time. Moreover, the coexistence of a series of underlying diseases associated with AHA should be always searched for. An early recognition and an adequate treatment of this coagulation disorder and of the possible associated diseases play a significant role for a favourable outcome, but concomitant morbidities in the elderly may limit aggressive therapy and may complicate the clinical scenario. We report 3 consecutive elderly patients successfully treated with recombinant activated factor VII and standard immunosuppressive regimens, with remission of the disease.

Diabetes mellitus and acquired haemophilia: new association?

“…It has an estimated incidence of 1.3 to 1.5 per million/year, although many authors believe that this may be an underestimation since up to 20% of all cases are never diagnosed 5. It develops due to an acquired deficiency of CF secondary to anti-CF antibodies (‘inhibitor’) 6. These antibodies are usually polyclonal IgGs and target more frequently factor VIII.…”

Acquired haemophilia A: the importance of early recognition in cases of spontaneous bleeding in the elderly

“…There are a number of reasons for the higher mortality observed in this age group including diagnostic delay as a result of poor recognition of the condition compounded by presence of comorbid conditions, and use of concomitant drug therapy which can be a cause of bleeding in the elderly. In addition, drug intolerance, adverse drug effects and performance status may preclude the use of effective therapy 8. Approximately 50% of cases are idiopathic, but associations have been demonstrated with autoimmune disease, drugs (eg, penicillin), pregnancy and malignancy,9 the latter more common with increasing age.…”

Acquired hemophilia: a rare but life-threatening potential cause of bleeding in the intensive care unit

“…Although the incidence of AH in the general population ranges from 1 to 4 cases per million per year [8], the incidence increases with age (6.0 per million per year among those aged 65-85 years and 16.6 per million per year among those over the age of 85 years) [12]. In fact, Administration of hetastarch for volume expansion is an independent risk factor for coagulopathy Massive preoperative transfusion Pre-existing antiplatelet or anticoagulant therapy Pre-existing liver or renal dysfunction Intraoperative and/or postoperative factors Tissue injury Massive intraoperative or postoperative hemorrhage Massive intraoperative or postoperative transfusion Cardiopulmonary bypass for complex cardiac surgery Therapeutic heparinization Failure to reverse or manage preoperative treatment with antiplatelet or anticoagulant agents CPB Cardiopulmonary bypass, DIC disseminated intravascular coagulation, FFP fresh frozen plasma, PRBCs packed red blood cells, TPN total parenteral nutrition the median age at diagnosis ranges from 55 to 78 years [7], making AH a disease of primarily the elderly, a factor that contributes to the high morbidity and mortality of this condition.…”

“…In this study, which can easily be performed in any laboratory [12], plasma from an affected patient is incubated with an equal volume of normal plasma, resulting in normalization of the aPTT if there is a factor or VWF deficiency but only partial or no correction when a factor-directed inhibitor or lupus anticoagulant is present. In the case of a factor VIIIdirected inhibitor, however, a mixing study may yield misleading results if not performed under proper conditions.…”

“…Factor VIII inhibitors are time-and temperaturedependent, and the action of these inhibitors is often delayed [14,15,25]. Therefore, assessment of the aPTT immediately after mixing and after an incubation period of 2 h is recommended; a more prolonged aPTT after 1-2 h versus the immediate mix is suggestive of a factor VIII inhibitor [12,15,25]. Acquired hemophilia is essentially confirmed by the additional documentation of reduced factor VIII activity (typically to 0-15% of normal values), along with quantification of the factor VIII inhibitor by the Bethesda assay [26].…”