International recommendations on the diagnosis and treatment of patients with acquired hemophilia A (original) (raw)
Related papers
Consensus recommendations for the diagnosis and treatment of acquired hemophilia A
BMC Research Notes, 2010
Background: Acquired hemophilia A (AHA) is a rare bleeding disorder caused by an autoantibody to coagulation factor (F) VIII. It is characterized by soft tissue bleeding in patients without a personal or family history of bleeding. Bleeding is variable, ranging from acute, life-threatening hemorrhage, with 9-22% mortality, to mild bleeding that requires no treatment. AHA usually presents to clinicians without prior experience of the disease, therefore diagnosis is frequently delayed and bleeds under treated.
Acquired hemophilia A: Diagnosis, aetiology, clinical spectrum and treatment options
Autoimmunity Reviews, 2011
Acquired hemophilia A (AHA) is a rare disorder with an incidence of approximately 1 per million/year with a high mortality rate of more than 20%. The disease occurs due to autoantibodies against coagulation factor VIII (FVIII) which neutralize its procoagulant function and result in severe, often life-threatening bleeding. The antibodies arise in individuals with no prior history of hemophilia A. AHA may be associated with pregnancy, autoimmune diseases, malignancy, infections or medication and occurs most commonly in the elderly. Approximately 50% of the patients remain idiopathic with no known underlying pathological condition. Clinical manifestations include spontaneous hemorrhages into the skin, muscles or soft tissues or excessive bleeding during surgery. Hemarthrosis which is the hallmark of congenital severe hemophilia A seldom occurs in AHA. The diagnosis of AHA is based on the isolated prolongation of activated partial thromboplastin time (APTT) which does not normalize after the addition of normal plasma along with reduced FVIII levels. The treatment involves two aspects-eradication of antibodies and maintaining effective hemostasis during a bleeding episode. The protocols for eradication of antibodies include immunoadsorption, immunosuppression or immune tolerance induction (ITI). The treatment of acute bleeding episodes involves use of different bypassing agents like recombinant activated factor VIIa (rFVIIa, NovoSeven®) and activated prothrombin complex concentrate (aPCC, (FEIBA®) in case of patients with high titer inhibitors or with antifibrinolytics,1deamino-8-D-arginine vasopressin (DDAVP) or FVIII concentrates in low titer inhibitor patients. The anti CD20 monoclonal antibody, rituximab, has shown very good results either singly or in combination with immunosuppressive regimens in patients who do not respond to standard immunosuppressors. The present review summarizes the diagnostic, aetiological, clinical and treatment aspects of AHA focusing on the recent advances in this area.
Acquired hemophilia A: Updated review of evidence and treatment guidance
American Journal of Hematology, 2017
Acquired hemophilia A (AHA) is a rare disease resulting from autoantibodies (inhibitors) against endogenous factor VIII (FVIII) that leads to bleeding, which is often spontaneous and severe. AHA tends to occur in elderly patients with comorbidities and is associated with high mortality risk from underlying comorbidities, bleeding, or treatment complications. Treatment, which consists of hemostatic management and eradication of the inhibitors, can be challenging to manage. Few data are available to guide the management of AHA-related bleeding and eradication of the disease-causing antibodies. Endorsed by the Hemostasis and Thrombosis Research Society of North America, an international panel of experts in AHA analyzed key questions, reviewed the literature, weighed the evidence and formed a consensus to update existing guidelines. AHA is likely underdiagnosed and misdiagnosed in real-world clinical practice. Recommendations for the management of AHA are summarized here based on the available data, integrated with the clinical experience of panel participants.
Acquired hemophilia A: a review of recent data and new therapeutic options
Hematology (Amsterdam, Netherlands), 2017
Acquired hemophilia A (AHA) is a rare, but potentially life-threatening, bleeding disorder caused by an autoantibody against factor VIII that interferes with its coagulant function. We performed a narrative review focusing on the diagnostic aspects of AHA and on the current treatment strategies with particular regard to new data and therapeutic developments. The management of this severe hemorrhagic disorder is based on the control of bleeding with the use of bypassing agents and on the utilization of a variety of immunosuppressant agents with the goal of eliminating the autoantibody permanently. The optimal management of AHA should be multidisciplinary and requires a close collaboration between physicians from various specialties.
Challenges and open issues in the management of acquired hemophilia A (AHA)
Blood cells, molecules & diseases, 2015
Acquired hemophilia A (AHA) is a rare autoimmune bleeding disorder caused by antibodies which neutralize the function of factor VIII (FVIII). The disease presents a complex clinical challenge to the treating Physicians and Hematologists. As the disease is associated with high mortality, prompt management is necessary. Early recognition, quick diagnosis and timely referral to a specialized center are important for better management of these patients. The different clinical manifestations, underlying pathology, inhibitor kinetics and the associated age related comorbidities do not allow extrapolation of the treatment protocols of congenital hemophilia to AHA. The basic strategies of the management of AHA patients involve maintaining hemostasis, suppression or eradication of antibodies, diagnosis and treatment of underlying pathology and avoid treatment related complications like thrombosis. The efficiency of hemostatic agents which are generally used to treat AHA is unpredictable. Due...
Blood, 2012
Acquired hemophilia A is a rare bleeding disorder caused by autoantibodies to coagulation FVIII. Bleeding episodes at presentation are spontaneous and severe in most cases. Optimal hemostatic therapy is controversial, and available data are from observational and retrospective studies only. The EACH2 registry, a multicenter, pan-European, Web-based database, reports current patient management. The aim was to assess the control of first bleeding episodes treated with a bypassing agent (rFVIIa or aPCC), FVIII, or DDAVP among 501 registered patients. Of 482 patients with one or more bleeding episodes, 144 (30%) received no treatment for bleeding; 31 were treated with symptomatic therapy only. Among 307 patients treated with a first-line hemostatic agent, 174 (56.7%) received rFVIIa, 63 (20.5%) aPCC, 56 (18.2%) FVIII, and 14 (4.6%) DDAVP. Bleeding was controlled in 269 of 338 (79.6%) patients treated with a first-line hemostatic agent or ancillary therapy alone. Propensity score matchin...
Acquired Hemophilia A: A Permanent Challenge for All Physicians
Medicines
Acquired hemophilia A (AHA) is a rare disease with a prevalence in Europe of 1.5 per million. This diagnosis is significantly delayed in about one-third of all cases, leading to deferred treatment. The main signs of AHA are spontaneous bleeding seen in about two-thirds of all patients. AHA can be lethal in 20% of all symptomatic cases. This patient population’s main standard laboratory finding is a prolonged aPTT (activated prothrombin Time) with otherwise normal coagulation results. In addition, antibodies against FVIII (in Bethesda Units) and a quantitative reduction of FVIII activity are necessary to confirm AHA. The therapy of acute bleeding related to AHA is based on the following main principles: Pharmacologic control of the bleeding is of absolute importance. It can be achieved by administering either recombinant activated FVIIa “bypass therapy”; activated prothrombin complex; or Emicizumab, a bispecific monoclonal antibody. Eradication of the FVIII antibodies should be initi...
Acquired hemophilia A: a frequently overlooked autoimmune hemorrhagic disorder
Journal of immunology research, 2014
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 con...
Acquired Hemophilia: An Overview on Diagnosis and Treatment
The Open Atherosclerosis & Thrombosis Journal, 2009
Acquired hemophilia (AH) is a rare but severe bleeding diathesis characterized by autoantibodies against a clotting factor, in most cases Factor VIII (FVIII). This bleeding disorder occurs more frequently in the elderly and may be associated with several conditions, such as malignancies, autoimmune diseases, postpartum or drugs; however, about half of cases remain idiopathic. At variance with congenital hemophilia, in which hemarthroses are the most common bleeding manifestations, in patients with AH hemorrhages involving soft tissues (muscle, skin) are more frequently reported. AH is diagnosed in patients without previous personal or family bleeding history in which prolonged activated partial thromboplastin time is not corrected after mixing and incubating for 2-4 hours at 37°C equal volumes of patient and normal plasma, FVIII:C levels are reduced and a specific FVIII inhibiting activity is detected and measured by the Bethesda assay or its Nijmegen modification. A prompt recognition of this life-threatening bleeding disorder and an early and aggressive treatment are mandatory, as diagnostic delays or inadequate treatments are associated with high mortality rates (up to 44% in literature). Therapeutic approach of AH is devoted to stop acute bleeds and to eradicate the FVIII autoantibody. Bleeding episodes can be treated with FVIII concentrates or desmopressin in patients with low titer inhibitors, but FVIII bypassing agents (activated prothrombin complex concentrates and recombinant activated FVIIa) are required for those with high-titer inhibitors or more severe bleeds. Steroids alone or in combination with cyclophosphamide are effective for eradicating autoantibodies in most cases. More recently, increasing evidence suggests a role for rituximab in this setting, in particular as a second-line approach.
Management of Acquired Hemophilia: A Literature Review
Acquired hemophilia is a rare, but often severe, bleeding disorder caused by autoantibodies against a coagulation factor, usually factor VIII (FVIII). The most common clinical presentations are diffuse bruising, soft tissue bleeds, and hematuria. As acquired hemophilia is associated with severe bleeding complications with high mortality, early diagnosis and intervention are crucial. The bypassing agents, recombinant activated factor VII (rFVIIa) and activated prothrombin complex concentrate (aPCC), have been shown to be effective as firstline treatment for bleeds, and treatment should be switched to the other product if the first choice fails. Starting immune therapy to eradicate the autoantibodies should not be postponed. The combination of oral corticosteroids and cyclophosphamide is effective in eradicating the neutralizing autoantibodies, and should probably be the choice for first-line treatment. Rituximab is a promising drug in acquired hemophilia, but should perhaps be limited to second-line treatment.