Inhibitor development in patients with type 3 Von Willebrand disease, a comprehensive study on 99 Iranian patients

Jazebi, Mohammad; Baghaipour, Mohammad Reza; Bahoush, Gholamreza; Ala, F.; Dorgalaleh, Akbar; Asl, Seyedeh Somayeh Moazezi Nekoei; Bahraini, Mehran; Baghaipour, Nazanin; Tabibian, Shadi

doi:10.1111/hae.14266

Cited by 3 publications

(1 citation statement)

References 9 publications

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“…Subsequently, more studies on type 3 VWD with inhibitors were reported (14). A recently large study on 99 Iranian patients with type 3 VWD reported 19.2% positivity for VWF inhibitors, which is substantially higher than the earlier reports (15). Most of the reports of VWF inhibitors were from patients with partial or complete VWF gene deletions.…”

Section: Discussionmentioning

confidence: 93%

Rare Occurrence of Inhibitors in Von Willebrand Disease: A Case Report

et al. 2022

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Introduction: Type 3 Von Willebrand Disease (VWD) is the least common but the most severe form of a disease, with a prevalence of about 0. 5 to 1 per million in Western countries. The prevalence of type 3 VWD in the developing countries, with a high degree of consanguinity, is about 6 per million. Moreover, due to underdiagnosis of the milder cases, the prevalence of type 3 VWD is about 50% of the cases. Rarely, some patients develop the Von Willebrand Factor (VWF) inhibitors, which may subsequently develop severe anaphylactic reactions on further exposure to the VWF containing factor replacement therapy. The prevalence of inhibitor development in patients with type 3 VWD has been shown to be in the range of 5.8 to 9.5%. In the absence of a gold standard assay for the quantitation of VWF inhibitors, a correct diagnosis and management of these patients are often challenging.Objectives: The objective of this study is to standardize the Bethesda assay for the VWF inhibitors and to estimate the VWD inhibitor titer in two cases of congenital type 3 VWD, which developed the VWF inhibitors.Results and Conclusions: We could successfully standardize the Bethesda assay for the quantitation of VWF inhibitors in two patients with congenital type 3 VWD with inhibitors.

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Section: Discussionmentioning

confidence: 93%

Rare Occurrence of Inhibitors in Von Willebrand Disease: A Case Report

et al. 2022

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Prevalence and characterization of anti-VWF antibodies in a population of patients with type 3 VWD

Perry,

Christopherson,

Agostini

et al. 2024

Blood Advances

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Von Willebrand disease (VWD) is an inherited bleeding disorder caused by quantitative or qualitative defects in the von Willebrand factor protein (VWF). Type 3 VWD has a severe bleeding phenotype caused by the absence of VWF where treatment usually involves replacement therapy with VWF-containing products. The immune system can react to the VWF product and form anti-VWF antibodies to neutralize or clear the VWF which can compromise efficacy of treatment or lead to anaphylaxis. Current diagnostic testing is limited to the detection of anti-VWF antibodies that neutralize VWF binding to platelets by using a ristocetin cofactor assay. We set out to develop assays to identify both neutralizing and non-neutralizing antibodies to screen, quantify, and characterize anti-VWF antibodies in samples from the Zimmerman Program, a large multicenter study of VWD subjects. We detected anti-VWF IgG or IgM antibodies in 18% of 49 unrelated type 3 VWD individuals. The antibodies ranged in concentration and consisted of 33% non-neutralizing and 67% neutralizing to factor VIII, collagen III, platelet GPIbα, and/or collagen IV binding. Of the positive type 3 VWD samples, 8/9 were IgG which were further subclassified into mostly IgG1 and IgG4 antibodies. Through a series of testing methods, we identified VWF specific antibodies in 9 unrelated type 3 VWD individuals with varying demographics, bleeding phenotypes, and genetic variants. This anti-VWF antibody testing strategy provides a useful tool to assess risk and better navigate treatment options for type 3 VWD patients.

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Dental Considerations in Children with Inherited Bleeding Disorders and Inhibitors: A Systematic Review

Vujkov,

Bajkin,

Blagojević

et al. 2024

JCM

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Background/Objectives: This systematic review evaluates the effectiveness of various hematological treatment protocols and local hemostatic measures in preventing oral bleeding and other complications during and after dental treatments in children with inherited bleeding disorders and inhibitors. Methods: This study was registered in the PROSPERO database. The comprehensive search strategy for this systematic review was conducted across five databases, namely, PubMed, Google Scholar, Web of Science, Scopus, and Cochrane Library. The search was aimed at identifying relevant literature published from January 2000 up to February 2024. Eligible studies included those with various designs, such as randomized controlled trials (RCTs), observational studies, cohort studies, case–control studies, and cross-sectional studies. Data extraction was carried out systematically, and relevant information on study characteristics, interventions, treatment protocols, local measures, complications, and outcomes was collected. Results: The systematic review included a total of five studies, encompassing participants ranging from ages of 2 to 18 years. These studies varied in their scope, with some focusing on hemophilia A with inhibitors while others addressed broader inherited bleeding disorders. The interventions examined included various prophylactic and treatment measures such as Emicizumab, recombinant factor VIIa, and local hemostatic measures. The study outcomes primarily assessed the efficacy of these interventions in preventing postoperative bleeding and improving quality of life. Emicizumab has significantly shifted the treatment paradigm for children with inherited bleeding disorders and inhibitors. This prophylactic treatment has been associated with a marked reduction in the frequency of bleeding episodes, fewer hospital admissions for bleeding management, and enhanced participation in daily activities. Conclusions: This review highlights gaps in the management of dental care in children with inherited bleeding disorders and inhibitors. It underscores the need for standardized protocols that integrate new prophylactic treatments such as Emicizumab. Our findings suggest that adopting updated protocols can significantly reduce bleeding complications during dental procedures.

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Inhibitor development in patients with type 3 Von Willebrand disease, a comprehensive study on 99 Iranian patients

Cited by 3 publications

References 9 publications

Rare Occurrence of Inhibitors in Von Willebrand Disease: A Case Report

Rare Occurrence of Inhibitors in Von Willebrand Disease: A Case Report

Prevalence and characterization of anti-VWF antibodies in a population of patients with type 3 VWD

Dental Considerations in Children with Inherited Bleeding Disorders and Inhibitors: A Systematic Review

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