Treatment of acquired haemophilia with recombinant activated FVII: A critical appraisal

Novo Nordisk, København, Capital Region, Denmark
Haemophilia (Impact Factor: 2.6). 10/2007; 13(5):451-61. DOI: 10.1111/j.1365-2516.2007.01474.x
Source: PubMed


Acquired haemophilia is a rare bleeding disorder usually caused by the spontaneous formation of inhibitory antibodies to coagulation FVIII. The disease occurs most commonly in the elderly, and although acquired haemophilia may be associated with a variety of underlying conditions, up to 50% of reported cases are idiopathic. Treatment options have traditionally involved human FVIII or FIX replacement therapy (if the inhibitor titre allows), porcine FVIII or the use of activated pro-thrombin complex concentrates. Recombinant activated coagulation FVII (rFVIIa) was available on an emergency and compassionate use basis from 1988 to 1999 at sites in Europe and North America. It has been registered in Europe for use in treating acquired haemophilia since 1996 and has recently been licensed for this indication in the United States. By directly activating FX on the surface of activated platelets at the site of injury (thereby bypassing FVIII and FIX), rFVIIa can circumvent the actions of inhibitory antibodies present in acquired haemophilia patients. This paper provides an overview of experiences with rFVIIa for the treatment of acquired haemophilia from the NovoSeven compassionate and emergency use programmes (1989-1999), the Hemophilia and Thrombosis Research Society Registry, and independent published reports from January 1999 to September 2005. rFVIIa has been reported to provide safe and effective haemostasis as a first line therapy in patients of all ages for a variety of surgical and non-surgical bleeding situations.

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    • "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 [67]. "
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    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.
    Full-text · Article · Mar 2014 · Journal of Immunology Research
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    • "Both recombinant activated factor VII (rFVIIa) and the activated Prothrombin complex concentrate (aPCC) factor 8 inhibitor bypassing activity (FEIBA®) is proven to be effective first line treatment in AHA (5, 9, 10). Goudemand et al. reviewed the use of FEIBA® for the treatment of patients with AHA. "
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    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.
    Full-text · Article · Feb 2014 · Anesthesiology and Pain Medicine
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    • "Treatment with either rFVIIa or FEIBA is associated with arterial and venous thrombosis and the incidence of thrombosis appears to be higher than when these agents are used in congenital haemophilia A. This is probably due to risk factors associated with the age and the often complex clinical status of these patients. A review of patients with AHA treated with rFVIIa reported 12 thrombotic events, predominantly arterial, in 139 patients (8Á6%) (Sumner et al, 2007). EACH2 reported 11 thrombotic events (seven arterial and four venous) in patients treated with a haemostatic agent and two in patients not treated with a haemostatic agent. "

    Full-text · Article · Jul 2013 · British Journal of Haematology
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