Acquired haemophilia A as a cause of recurrent bleeding episodes in the elderly

Acquired inhibitors against coagulation factor VIII (FVIII), also termed acquired haemophilia A, neutralize its procoagulant function and result in severe or often life-threatening bleeding. The antibodies arise in individuals with no prior history of clinical bleeding. Acquired haemophilia occurs rarely with the incidence of approximately 1 to 4 per million/ year, with severe bleeds in up to 90% of affected patients, and high mortality between 8-22%. About 50% of diagnosed patients were previously healthy, while the remaining cases may be associated with postpartum period, autoimmune diseases, malignancy, infections, or medications. Most patients have spontaneous haemorrhages into the skin, muscles or soft tissues, and mucous membranes, or after trauma and surgery, whereas haemarthroses are uncommon. The diagnosis of acquired haemophilia A based on the prolongation of activated partial thromboplastin time which does not normalize after the addition of normal plasma, reduced FVIII, with evidence of FVIII inhibitor measured by the Bethesda assay (Nijmegen modification). The treatment of acute bleeding episodes and the long-term eradication of the autoantibodies in acquired haemophilia are the main therapeutic strategy. Two options are currently available for acute bleeding control: the use rFVIIa or FEIBA in patients with higher inhibitor titer (>5 BU), or to raise the level of FVIII by administration of DDAVP or concentrates of FVIII in patients with low level of inhibitors (<5 BU). Treatment with FEIBA (50-100 IU/ kg every 8-12 hours) has shown good haemostatic response in 76-89% of the bleeding episodes. Patients treated with rFVIIa (90 ?g/kg every 2-6 hours) have achieved good response in 95-100% as a first-line, and 75-80% as a salvage therapy. Patients with low inhibitor titer and lower response can be treated with concentrate of FVIII in the recommended dose of 40 IU/kg plus 20 IU/kg for each BU of inhibitor. The treatment of non-life-threatening haemorrhages with desmopressin (DDAVP 0.3 ?g/kg) may increase both FVIII and vWF. Sometimes inhibitors disappear spontaneously, but longterm management is necessary for eradication of inhibitors by immunosuppression (prednisone 1 mg/kg 3 weeks alone or in combination cyclophosphamide 2 mg/kg), immunomodulation, intravenous immunoglobulin (HD IgG 2g/kg 2 or 5 d), physical removal of antibodies (plasmapheresis or immunoadsorption), or various combinations. Recently, a therapy with rituximab, an anti-CD20 monoclonal antibody, has shown to be effective in acquired haemophilia.

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Anticoagulation for Stroke Prevention after Restoration of Haemostasis with Emicizumab in Acquired Haemophilia A

European Journal of Case Reports in Internal Medicine ◽

10.12890/2021_002894 ◽

2021 ◽

Author(s):

Kadhim Al-Banaa ◽

Nicolas Gallastegui-Crestani ◽

Annette von Drygalski

Keyword(s):

Atrial Fibrillation ◽

Factor Viii ◽

Stroke Prevention ◽

The Elderly ◽

High Titre ◽

Haemophilia A ◽

Acquired Haemophilia ◽

Inhibiting Factor ◽

Life Threatening

Acquired haemophilia A (AHA) is a rare haemorrhagic disorder caused by the development of autoantibodies inhibiting factor VIII function. It predominantly affects the elderly, who are often burdened with a considerable number of comorbidities, and can result in life-threatening bleeding. The management of AHA consists of two aspects: inhibitor eradication with an immunomodulator and bleed control with a bypassing agent. Here we present a case of AHA with a high titre inhibitor in a patient with extensive comorbidities and atrial fibrillation in whom inhibitor eradication could not be achieved within a few weeks using corticosteroids alone. Due to coronavirus disease (COVID)-19 restrictions and complications of care, emicizumab offered an effective and convenient therapy, not only sparing the need for continued and intensified inhibitor eradication, but also allowing anticoagulation for stroke prophylaxis.

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ACQUIRED HAEMOPHILIA A: AN INTRIGUING DISEASE

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2020.045 ◽

2020 ◽

Vol 12 (1) ◽

pp. e2020045

Author(s):

Maria Gabriella Mazzucconi ◽

Erminia Baldacci ◽

Antonietta Ferretti ◽

Cristina Santoro

Keyword(s):

Eradication Therapy ◽

Diagnostic Algorithm ◽

The Elderly ◽

Haemophilia A ◽

Thrombin Time ◽

Small Peak ◽

Acquired Haemophilia ◽

Fviii Activity ◽

Therapeutic Tools ◽

Recombinant Fviii

Acquired Haemophilia A is a rare acquired bleeding disorder caused by autoantibodies directed against Factor VIII, which neutralize 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 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 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 bypassing 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.

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A case of serious bleeding

Clinical Management Issues ◽

10.7175/cmi.v5i2s.1106 ◽

2015 ◽

Vol 5 (2S) ◽

pp. 15-19

Author(s):

Irene Ricca ◽

Marisa Coggiola ◽

Silvia Destefanis ◽

Claudio Pascale

Keyword(s):

Mortality Rate ◽

Autoimmune Diseases ◽

Factor Viii ◽

Coagulation Factor ◽

The Elderly ◽

Severe Anaemia ◽

Severe Bleeding ◽

Haemophilia A ◽

Acquired Haemophilia ◽

History Of

Acquired haemophilia A (AHA) is a rare disorder with a high mortality rate. It occurs due to autoantibodies against coagulation factor VIII (FVIII) which neutralise its procoagulant function resulting in severe bleeding. This disease may be associated with autoimmune diseases, malignancies, infections or medications and occurs most commonly in the elderly. Diagnosis is based on the isolated prolongation of aPTT which does not normalise after the addition of normal plasma along with reduced FVIII levels. Treatment involves eradication of antibodies and maintaining effective haemostasis during bleeding. We report a case of a 76-year-old patient with a history of haemorrhage with severe anaemia. The article describes difficulties and complexities of clinical and therapeutic management of the patient.

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Acquired haemophilia A: A 2013 update

Thrombosis and Haemostasis ◽

10.1160/th13-05-0363 ◽

2013 ◽

Vol 110 (12) ◽

pp. 1114-1120 ◽

Cited By ~ 59

Author(s):

Massimo Franchini ◽

Pier Mannucci

Keyword(s):

Drug Exposure ◽

Current Knowledge ◽

Post Partum ◽

Coagulation Factor ◽

The Elderly ◽

Bleeding Disorder ◽

Severe Bleeding ◽

Haemophilia A ◽

Autoantibody Production ◽

Acquired Haemophilia

SummaryAcquired haemophilia A (AHA) is a rare but often severe bleeding disorder caused by autoantibodies against coagulation factor VIII (FVIII). AHA occurs more frequently in the elderly and in association with several conditions, such as the post-partum period, malignancies, autoimmune diseases or drug exposure; however, approximately 50% of reported cases are apparently idiopathic. Beside the elimination of the underlying disorder, the therapeutic approach to AHA should be directed toward the control of acute bleed and the eradication of FVIII autoantibody production. In this narrative review, we summarise the current knowledge on the epidemiology, diagnosis and clinical features of AHA, focusing in particular on advances in the management of this challenging bleeding disorder.

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Acquired haemophilia in the elderly is a severe disease: report of five new cases

Haemophilia ◽

10.1046/j.1365-2516.2001.00531.x ◽

2001 ◽

Vol 7 (4) ◽

pp. 428-432 ◽

Cited By ~ 20

Author(s):

S. Godreuil ◽

R. Navarro ◽

P. Quittet ◽

L. Landreau ◽

J-F. Schved ◽

...

Keyword(s):

Severe Disease ◽

The Elderly ◽

Acquired Haemophilia

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Clinical features and outcome of acquired haemophilia A

Hämostaseologie ◽

10.1055/s-0037-1619050 ◽

2010 ◽

Vol 30 (03) ◽

pp. 156-161 ◽

Cited By ~ 9

Author(s):

R. Gheisari ◽

B. Bomke ◽

T. Hoffmann ◽

R. E. Scharf

Keyword(s):

Respiratory Diseases ◽

Care Center ◽

Treatment Algorithm ◽

Early Death ◽

Underlying Disease ◽

Pulmonary Sarcoidosis ◽

Relative Increase ◽

Laboratory Evaluation ◽

Haemophilia A ◽

Acquired Haemophilia

SummaryWe have performed a monocenter study on 29 consecutive patients with acquired haemophilia A who were referred for diagnosis and treatment to the Düsseldorf Haemophilia Comprehensive Care Center between March 2001 and February 2010. Patients, methods: 18 men (age: 44–86 years) and 11 women (age: 20–83 years). For laboratory evaluation, a standardized staged protocol of aPTT, FVIII : C activity and concentration, mixing studies with patient and normal plasma, and quantification of inhibitor titers (Bethesda assay) was used. Diagnostic work-up included elaborate examinations for any underlying disease. Results: In 18 (62%) of the 29 patients with acquired haemophilia A, an underlying disorder was identified, including 9 patients with respiratory diseases (31%), 7 patients with autoimmune disorders (24%), one with malignancy, and one with postpartum state, while in 11 patients (38%) acquired haemophilia A remained idiopathic. Haemotherapy of bleeding, suppression or elimination of the inhibitor, and induction of immunotolerance to endogenous FVIII:C were performed according to a treatment algorithm. Predefined clinical endpoints were control of bleeding, eradication of the inhibitor, complete or partial remission (CR, PR), relapse, or early death (≤30 days). Of the 29 patients in total, 22 individuals achieved CR (76%), three had PR, one relapsed, and three died within 30 days (one of acute myocardial infarction while on anti-haemorrhagic treatment, one of sepsis while on immunosuppression due to active acquired haemophilia A, one of lung bleeding in association with pre-existing pulmonary sarcoidosis). Conclusion: This monocenter study demonstrates that control of life-threatening bleeding, eradication of the inhibitor, and induction of tolerance to endogenous FVIII have significantly improved the clinical outcome of acquired haemophilia A. Our data also suggest a shift in underlying disorders associated with acquired haemophilia A, whereby, in comparison to published studies, a relative increase in the proportion of patients with respiratory diseases is present.

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