Emicizumab in the Treatment of Acquired Haemophilia: A Case Report

Möhnle, Patrick; Pekrul, Isabell; Spannagl, Michael; Sturm, Andreas; Singh, Delila; Dechant, Claudia

doi:10.1159/000497287

Cited by 29 publications

(46 citation statements)

References 9 publications

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“…56 The drug has been used in a few patients with AHA with severe bleeding. 57,58 However, the safety and efficacy of emicizumab in AHA is unknown and so this antibody should not be used in this group of patients outside of clinical trials. This is particularly relevant for elderly patients, in whom cardiovascular events are more common, and in women who are considering use of hormonal therapy or future pregnancy, as emicizumab is an IgG4 antibody and may therefore be transferred across the placenta.…”

Section: Anti-fibrinolytics and Other Treatmentsmentioning

confidence: 99%

International recommendations on the diagnosis and treatment of acquired hemophilia A

et al. 2020

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A cquired hemophilia A (AHA), a rare bleeding disorder caused by neutralizing autoantibodies against coagulation factor VIII (FVIII), occurs in both men and women without a previous history of bleeding. Patients typically present with an isolated prolonged activated partial thromboplastin time due to FVIII deficiency. Neutralizing antibodies (inhibitors) are detected using the Nijmegen-modified Bethesda assay. Approximately 10% of patients do not present with bleeding and, therefore, a prolonged activated partial thromboplastin time should never be ignored prior to invasive procedures. Control of acute bleeding and prevention of injuries that may provoke bleeding are top priorities in patients with AHA. We recommend treatment with bypassing agents, including recombinant activated factor VII, activated prothrombin complex concentrate, or recombinant porcine FVIII in bleeding patients. Autoantibody eradication can be achieved with immunosuppressive therapy, including corticosteroids, cyclophosphamide and rituximab, or combinations thereof. The median time to remission is 5 weeks, with considerable interindividual variation. FVIII activity at presentation, inhibitor titer and autoantibody isotype are prognostic markers for remission and survival. Comparative clinical studies to support treatment recommendations for AHA do not exist; therefore, we provide practical consensus guidance based on recent registry findings and the authors' clinical experience in treating patients with AHA.

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Section: Anti-fibrinolytics and Other Treatmentsmentioning

confidence: 99%

International recommendations on the diagnosis and treatment of acquired hemophilia A

et al. 2020

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“…More recently, the clinical benefits of emicizumab have been documented in some AHA patients with unresolved severe bleeding. [19][20][21][22] These reports also recorded a fatality, however, in one patient treated with emicizumab on compassionate grounds. 22 The current clinical trials of emicizumab have not included patients with AHA, however, and reliable evidence-based data on the potential use of this therapy in AHA is warranted.…”

Section: Introductionmentioning

confidence: 95%

“…Pathophysiological concepts and studies using a primate monkey model of AHA have suggested that emicizumab might be useful for the hemostatic management of AHA as well as congenital HA. More recently, the clinical benefits of emicizumab have been documented in some AHA patients with unresolved severe bleeding . These reports also recorded a fatality, however, in one patient treated with emicizumab on compassionate grounds .…”

Section: Introductionmentioning

confidence: 99%

“…Alternatively, global coagulation assays including clot waveform analysis, thrombin generation assay, and rotational thromboelastometry have been reported as useful techniques for assessing hemostasis in these circumstances . The global coagulation effects of emicizumab in AHA patients remain unknown, however, although conventional assays in some cases with AHA treated with emicizumab have been reported . In the present study, we have assessed the coagulation potential of emicizumab ex vivo in plasma samples from AHA patients using a modern thrombin generation assay, based on a simulated model of AHA treatment.…”

Section: Introductionmentioning

confidence: 99%

“…[23][24][25] The global coagulation effects of emicizumab in AHA patients remain unknown, however, although conventional assays in some cases with AHA treated with emicizumab have been reported. [19][20][21][22] In the present study, we have assessed the coagulation potential of emicizumab ex vivo in plasma samples from AHA patients using a modern thrombin generation assay, based on a simulated model of AHA treatment.…”

Section: Introductionmentioning

confidence: 99%

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An anti‐factor IXa/factor X bispecific antibody, emicizumab, improves ex vivo coagulant potentials in plasma from patients with acquired hemophilia A

Takeyama

Nogami

Matsumoto

et al. 2020

Journal of Thrombosis and Haemostasis

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Introduction Acquired hemophilia A (AHA) is caused by autoantibodies against factor (F)VIII, and is characterized by severe, spontaneous bleeding, which can be life‐threatening. Emicizumab, an anti‐FIXa/FX bispecific antibody, significantly reduces bleeding events in congenital hemophilia A (HA) with and without inhibitors. The known pathophysiological mechanisms and current preclinical data in HA suggest that emicizumab could provide effective treatment for AHA, but the coagulation activities of emicizumab in these patients remain unknown. Aim To evaluate the coagulant effects of emicizumab in plasma from AHA patients. Methods and Results Tissue factor‐triggered thrombin generation assays using normal plasma preincubated with anti‐FVIII monoclonal antibodies recognizing different epitopes demonstrated that 20 µg/mL emicizumab recovered the depressed peak levels of thrombin generation to 46% to 72%. Further studies were devised, therefore, to simulate the clinical course in AHA patients, including during the acute phase for severe bleeding requiring FVIII‐bypassing therapy, and during the subacute/chronic phase with less bleeding. Various concentrations of emicizumab were used to represent the potential changes in plasma levels based on the half‐life of the antibody (~30 days). The ex vivo addition of emicizumab to plasma samples from AHA patients (n = 16) increased peak thrombin in all cases, irrespective of the inhibitor epitope specificity. Thrombin generation at 20 and 100 µg/mL emicizumab was restored to (median) 43.9% and 92.2%, respectively. Differences were evident in some cases, however, and recovery rates appeared likely to be greater in patients with type 2 inhibitor than those with type 1. Conclusion Emicizumab improved ex vivo coagulation potential in plasma from AHA patients.

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Recombinant porcine factor VIII in acquired hemophilia A: Experience from two patients and literature review

Hayden

Candelario

Moyer

2022

Research and Practice in Thrombosis and Haemostasis

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Background Acquired hemophilia A (AHA) is a disease caused by antibody formation inhibiting the function of factor VIII, causing bleeding. Recombinant porcine factor VIII (rpFVIII) escapes human FVIII antibody recognition and can provide life‐saving hemostasis. However, the development of antibodies against pFVIII can limit its use. We report two cases in which loss of response to rpFVIII occurred, likely because of inhibiting antibodies. In case 1, the patient achieved hemostasis but lost response to rpFVIII within a few days. In the second case, rpFVIII controlled bleeding but the patient experienced diminishing half‐life of rpFVIII infusions over time, necessitating a switch to emicizumab which provided lasting hemostasis. Key Clinical Question Based on our experience with these cases, we reviewed the available literature regarding the use of rpFVIII in AHA. The Key Clinical Question was to determine how often inhibitors were associated with rpFVIII treatment failure. Clinical approach and conclusions We identified 43 AHA patients across five studies who were treated with rpFVIII. Twenty‐two patients (51%) developed pFVIII inhibitors and seven cases (16%) reported loss of efficacy associated with an inhibitor. In conclusion, rpFVIII can be a life‐saving therapy in AHA. However, clinicians should be aware that pFVIII antibody development can reduce the efficacy and duration of response. Recombinant pFVIII’s limitations support the utility of further investigation of alternative therapies such as emicizumab in early AHA management.

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Emicizumab in the Treatment of Acquired Haemophilia: A Case Report

Cited by 29 publications

References 9 publications

International recommendations on the diagnosis and treatment of acquired hemophilia A

International recommendations on the diagnosis and treatment of acquired hemophilia A

An anti‐factor IXa/factor X bispecific antibody, emicizumab, improves ex vivo coagulant potentials in plasma from patients with acquired hemophilia A

Recombinant porcine factor VIII in acquired hemophilia A: Experience from two patients and literature review

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