Acquired hemophilia A is a rare bleeding diathesis caused by autoantibodies directed against clotting factor VIII and associated with an increased morbidity and mortality. This autoimmune disorder most commonly occurs in the elderly. Although it may be associated with several underlying pathologies, up to 50% of reported cases remain idiopathic. In contrast with congenital hemophilia, which is commonly characterized by hemarthroses, hemorrhages in patients with acquired hemophilia involve most frequently soft tissues. The 2 treatment priorities are to arrest the acute bleeding and to eradicate the factor VIII autoantibody. Acute bleeding episodes in patients with low-titer inhibitors can be treated using human factor VIII concentrates, whereas factor VIII bypassing agents, such as activated prothrombin complex concentrates or recombinant activated factor VII, are effective for the treatment of those with high-titer inhibitors. An analysis of the literature shows that the most effective first-line treatment for the eradication of factor VIII autoantibodies is the combination of steroids and cyclophosphamide. However, there is increasing evidence on the effectiveness of other treatment approaches, such as immune tolerance regimens and rituximab. If confirmed by large controlled studies, these innovative therapies might become a valid option for long-term eradication of factor VIII inhibitors.
"The first-line treatment for severe bleeding episodes, especially in patients with high titers of inhibitors, is administration of bypassing agents [63, 64]. Activated prothrombin complex concentrates (APCC) containing factors II (prothrombin), VII, IX, and X or recombinant activated factor VII are commonly administered and have shown to be beneficial in treating patients with AHA as well as congenital hemophilia A patients with inhibitors [63–66]. Use of the immunoadsorption technique for removal of high-titer inhibitors has also proven beneficial in AHA patients with acute, life-threatening bleeding . "
[Show abstract][Hide abstract] ABSTRACT: Acquired hemophilia A (AHA) is a rare hemorrhagic disease in which autoantibodies against coagulation factor VIII- (FVIII-) neutralizing antibodies (inhibitors) impair the intrinsic coagulation system. As the inhibitors developed in AHA are autoantibodies, the disease may have an autoimmune cause and is often associated with autoimmune disease. Although acute hemorrhage associated with AHA may be fatal and is costly to treat, AHA is often unrecognized or misdiagnosed. AHA should thus be considered in the differential diagnosis particularly in postpartum women and the elderly with bleeding tendency or prolonged activated partial thromboplastin time. Cross-mixing tests and measurement of FVIII-binding antibodies are useful to confirm AHA diagnosis. For treatment of acute hemorrhage, hemostatic therapy with bypassing agents should be provided. Unlike in congenital hemophilia A with inhibitors, in which immune tolerance induction therapy using repetitive infusions of high-dose FVIII concentrates is effective for inhibitor eradication, immune tolerance induction therapy has shown poor efficacy in treating AHA. Immunosuppressive treatment should thus be initiated to eradicate inhibitors as soon as the diagnosis of AHA is confirmed.
Journal of Immunology Research 03/2014; 2014:320674. DOI:10.1155/2014/320674 · 2.93 Impact Factor
"No underlying etiology is found in nearly 50% of all cases (2, 5). Patients with AHA tend to present with hemorrhage into the skin, mucous membranes, muscles, soft tissues, or as postpartum in contrast to congenital hemophiliacs in whom hemarthrosis is a typical presentation (6, 7). "
[Show abstract][Hide abstract] ABSTRACT: Acquired hemophilia A is a rare bleeding disorder with a high mortality rate. Diagnosis and treatment of this disorder can be very challenging to anesthesiologists because of lack of a personal or familial abnormal bleeding history.
We report a 60-year-old woman who presented to the operating room for an urgent fasciotomy. She was initially diagnosed to have compartment syndrome of her left upper extremity secondary to an expanding hematoma after multiple unsuccessful venipuncture attempts. After surgical intervention, she developed recurrent intramuscular hematomas, became severely anemic, and required surgical re-exploration and multiple blood product transfusions. Ultimately, she was found to have an elevated activated partial thromboplastin time (aPTT), very low FVIII activity, and high FVIII inhibitor titers consistent with the diagnosis of acquired hemophilia A.
Treatment strategies in acquired hemophilia are based on two major objectives. During the acute stage, effective control of bleeding is critical. The ultimate therapeutic goal during the subacute phase is the elimination of the inhibitors targeting factor VIII. Here, we present this case and will review current literature regarding therapeutic approaches to this rare condition in the operating room setting and postoperative course.
Anesthesiology and Pain Medicine 02/2014; 4(1):e11906. DOI:10.5812/aapm.11906
"In high-titre patients, bypassing agents such as recombinant factor VIIa or FVIII inhibitor bypass activity (FEIBA) are indicated . In patients with a low titre inhibitor (i.e., <5 Bethesda units or BU), plasma-derived or recombinant human FVIII can be used . "
[Show abstract][Hide abstract] ABSTRACT: This case report describes a patient with an idiopathic acquired Factor VIII inhibitor and severe bleeding. She was treated with rituximab after failing first-line treatment with steroids and cyclophosphamide. Two months following rituximab treatment, our patient developed a succession of severe opportunistic infections requiring intensive care unit admission. Over a period of 12 weeks she required treatment for
septicaemia, herpes simplex gingivostomatitis and pharyngotonsillitis, clostridium difficile-related diarrhoea, systemic cytomegalovirus infection, pneumocystis jiroveci, and invasive pulmonary aspergillosis lung infections. After significant rehabilitation, the patient was finally discharged following a 5-month admission. This case highlights the complexity of balancing a life-threatening condition with the side effects of treatment. It also raises the issue of routine prophylaxis for immunosuppression in nonmalignant conditions, which will become a common dilemma with the expanding indications for rituximab use.
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