The potential role of emicizumab prophylaxis in severe von Willebrand disease

Barg, Assaf Arie; Avishai, Einat; Budnik, Ivan; Brutman, Tamar Barazani; Tamarin, Ilia; Dardik, Rima; Bashari, Dalia; Misgav, Mudi; Lubetsky, Aharon; Lalezari, Shadan; Livnat, Tami; Kenet, Gili

doi:10.1016/j.bcmd.2020.102530

Cited by 15 publications

(57 citation statements)

References 28 publications

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“…Of the two patients negative for inhibitors, one patient despite being on prophylactic treatment with F VIII (Haemate P) 50 IU/Kg, two to three times weekly had recurrent hemarthrosis. 17 One patient with inhibitor continued to have spontaneous hemarthrosis despite regular prophylaxis with rFVIIa 270 µgm/kg thrice a week then daily FEIBA. Following treatment with emicizumab, he had no further spontaneous bleeding.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of emicizumab in von Willebrand disease (VWD) patients with and without alloantibodies to von Willebrand factor (VWF): Report of two cases and review of literature

Shanmukhaiah¹,

Jijina²,

Kannan

et al. 2022

Haemophilia

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Introduction: von Willebrand disease (VWD) is the common bleeding disorder with a clinically relevant bleeding prevalence of 1:10,000. von Willebrand disease patients lack both von Willebrand factor (VWF) and factor VIII (FVIII), which are critical for normal haemostasis. The conventional treatment for VWD includes desmopressin and replacement therapy with plasma derived FVIII with VWF concentrates or recombinant VWF. Development of alloantibodies is a rare occurrence, there is a paucity in the literature of treatment modalities in these patients. Not many reports are available in literature on the efficacy of emicizumab in VWD patients with or without alloantibodies to VWF. Aim:To do systematic review of literature on emicizumab in VWD and report our experience of emicizumab in two patients of VWD Methods: We used electronic search engines till May 2021 in 'Google scholar' and 'PubMed' , to collect the case reports or case series on use of emicizumab for management of VWD. Two of our severe VWD patients were successfully treated with emicizumab. A systematic review was performed and the results discussed. Results:The electronic search revealed six case reports using emicizumab for treatment of VWD. Two were in vitro studies and four in patients with VWD type 3 disease.In vitro studies and in VWD patients on emicizumab, showed improvement in thrombin generation and fibrin formation. Among four patients, three had alloantibodies to VWD and one was negative. All these patients were treated with emicizumab for 6-12 m. After starting emicizumab, none of them had spontaneous bleeding requiring treatment. During treatment with emicizumab, one patient had trauma-associated soft tissue hematoma, which was treated with rFVIIa and another patient had bleeding following dental exfoliation treated with Humate P. We treated two of our VWD patients one with and one without inhibitors with emicizumab after failure of other therapies.Both the patients showed marked improvement and continued to remain well and free of bleeding episodes. None of the patients had any thrombosis or thrombotic microangiopathy (TMA) during treatment with emicizumab.

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Section: Discussionmentioning

confidence: 99%

Efficacy of emicizumab in von Willebrand disease (VWD) patients with and without alloantibodies to von Willebrand factor (VWF): Report of two cases and review of literature

Shanmukhaiah¹,

Jijina²,

Kannan

et al. 2022

Haemophilia

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“…After screening citations on PubMed, EMBASE and Scopus by titles and abstracts, 60 full‐text and conference abstracts were screened for full‐text review for inclusion. Seventeen studies (11 full text, six conference abstracts) were included in the final review, for a total of 41 patients (33 AHA, eight type 3 VWD) 15–31 . The flowchart that describes our study selection is shown in Figure 1.…”

Section: Resultsmentioning

confidence: 99%

“…One patient with inhibitor received intravenous immunoglobulin as immunosuppressive therapy 27 . The remaining five patients had recurrent bleeds despite being on routine prophylaxis 30,31 . All type 3 VWD patients received the standard loading and maintenance dose of emicizumab.…”

Section: Resultsmentioning

confidence: 99%

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Off‐label use of emicizumab in persons with acquired haemophilia A and von Willebrand disease: A scoping review of the literature

2021

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Introduction Since the approval of emicizumab, a bispecific, factor VIII‐mimetic antibody, for use in persons with congenital haemophilia A in 2018, there have been increasing case reports and case series of off‐label use of emicizumab in other bleeding disorders, including acquired haemophilia A (AHA) and von Willebrand disease (VWD). Aim We conducted a scoping review on the use of emicizumab in AHA and VWD, focusing on the clinical presentation and outcomes. Methods We conducted a comprehensive search in PubMed, EMBASE and Scopus up to July 15, 2021. The following criteria were applied to the studies identified in the initial search: patients had a diagnosis of AHA or VWD; and the study reported on the clinical outcome of emicizumab use. Results Seventeen studies were included in the final review for a total of 41 patients (33 AHA, eight type 3 VWD). The majority of AHA patients and all type 3 VWD patients were started on emicizumab for active/recurrent bleeds. The dosing regimen of emicizumab used varied significantly in AHA patients. All patients had a clinical response to emicizumab use. One AHA patient developed a stroke on emicizumab use in association with concomitant recombinant FVIIa use for surgery. Data on adverse events from emicizumab use were not specifically reported in 24.4% of patients (four AHA, six type 3 VWD). Conclusion Based on published case reports and case series, emicizumab appears to be an effective haemostatic therapy for AHA and VWD. Larger confirmatory clinical trials are needed to confirm these findings.

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“…64 Although inhibitor development in VWD is much less frequent (5-10%) than in hemophilia A (30%), management of this rare complication is challenging. Emicizumab, a humanized bispecific antibody approved for the treatment of hemophilia A, has been used off-label for prophylaxis in a small number of patients with type 3 VWD with inhibitory alloantibodies, 65,66 because this product mimics the deficient coagulant activity of FVIII, even though it is without effect on VWF deficiency or dysfunction.…”

Section: Wilfactinmentioning

confidence: 99%

Prophylactic management of patients with von Willebrand disease

Franchini

Seidizadeh

Mannucci

2021

Therapeutic Advances in Hematology

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Von Willebrand disease, the most common inherited bleeding disorder that affects both males and females, is due to quantitative or qualitative defects of the multimeric glycoprotein von Willebrand factor, which cause mucous membrane bleeding but also soft tissue bleeding owing to the secondary deficiency of factor VIII. The aim of treatment is to correct this dual defect of hemostasis. In addition to the episodic management of bleeding episodes, therapy includes their short- or long-term prevention. Short-term prophylaxis is mainly warranted in order to provide effective hemostatic coverage to patients undergoing surgery or invasive procedures and to affected women at the time of delivery or during menstruations associated with excessive bleeding. The aim of long-term prophylaxis is to prevent bleeding in particular categories of patients at increased risk of frequent and spontaneous bleeding in the joints, nose, and gastrointestinal tract.

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The potential role of emicizumab prophylaxis in severe von Willebrand disease

Cited by 15 publications

References 28 publications

Efficacy of emicizumab in von Willebrand disease (VWD) patients with and without alloantibodies to von Willebrand factor (VWF): Report of two cases and review of literature

Efficacy of emicizumab in von Willebrand disease (VWD) patients with and without alloantibodies to von Willebrand factor (VWF): Report of two cases and review of literature

Off‐label use of emicizumab in persons with acquired haemophilia A and von Willebrand disease: A scoping review of the literature

Prophylactic management of patients with von Willebrand disease

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