更新于：2024-11-01

Von Willebrand Disease, Type 2

2型血管性血友病

更新于：2024-11-01

基本信息

别名

2型血管性血友病、Hereditary von Willebrand disease type 2、Hereditary von Willebrand disease type 2 (disorder)

+ [75]

简介

A subtype of von Willebrand disease that results from qualitative deficiencies of VON WILLEBRAND FACTOR. The subtype is divided into several variants with each variant having a distinctive pattern of PLATELET-interaction.

关联

项与 2型血管性血友病相关的药物

Efanesoctocog alfa

靶点

F10

作用机制

F10刺激剂

在研机构

赛诺菲（中国）投资有限公司 [+6]

原研机构

Amunix, Inc.

在研适应症

血友病A [+1]

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期2023-02-22

Rondaptivon Pegol

靶点

vWF

作用机制

vWF抑制剂

在研机构

Band Therapeutics LLC

原研机构

Band Therapeutics LLC

在研适应症

血友病A [+3]

非在研适应症

动脉粥样硬化 [+2]

最高研发阶段临床3期

首次获批国家/地区-

首次获批日期1800-01-20

HMB-002(Hemab Therapeutics)

靶点-

作用机制-

在研机构

Hemab Therapeutics ApS

原研机构

Hemab Therapeutics ApS

在研适应症

1型血管性血友病 [+1]

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

项与 2型血管性血友病相关的临床试验

NCT06610201 / RecruitingN/A

A Prospective, Screening Study of Bleeding and Treatment in Participants With Von Willebrand Disease

The purpose of this screening study is to accumulate information regarding bleeding events, quality of life, and the social and clinical impact of bleeds in participants with Von Willebrand Disease (VWD). Data from this study will be used to establish baseline bleeding and treatment rates in a population of participants with VWD and act as comparator data for future clinical study outcomes.

开始日期2024-08-30

申办/合作机构

Hemab ApS

[+1]

NCT04770935 / Completed临床1期

A Phase 1, Open-Label Study to Assess the Pharmacokinetics, and Safety and Tolerability of a Single Intravenous Injection of rFVIIIFc-VWF-XTEN (BIVV001) in Adults With Type 2N and 3 Von Willebrand Disease (VWD)

Primary Objective:
-To characterize the pharmacokinetics (PK) of BIVV001 after a single intravenous (IV) administration, as assessed by factor VIII (FVIII) activity determined by the one-stage activated partial thromboplastin time (aPPT) clotting assay, as well as, BIVV001 capture chromogenic Coatest FVIII activity assay
Secondary Objective:
-To assess the safety and tolerability of a single IV dose of BIVV001 in adult patients with type 2N and 3 VWD

开始日期2021-05-03

申办/合作机构

Bioverativ, Inc.

EUCTR2020-003807-32-AT / Not yet recruiting临床2期IIT

A Phase 2a Multiple Dose Basket Design” Study Of The Safety, Tolerability, And Pharmacologic Activity Of BT200 In Patients With Hereditary Bleeding Disorders - BT200-02

开始日期2020-12-16

申办/合作机构

Medical University of Vienna

100 项与 2型血管性血友病相关的临床结果

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100 项与 2型血管性血友病相关的转化医学

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0 项与 2型血管性血友病相关的专利（医药）

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902

项与 2型血管性血友病相关的文献（医药）

2024-10-01·Journal of Thrombosis and Haemostasis

Type 2N von Willebrand disease: genotype drives different bleeding phenotypes and treatment needs

Article

作者: Daniel, Mélanie Y ; Repessé, Yohann ; D'Oiron, Roseline ; Susen, Sophie ; Zawadzki, Christophe ; Veyradier, Agnès ; Paris, Camille ; Denis, Cécile V ; Babuty, Antoine ; Ternisien, Catherine ; Dupont, Annabelle ; Desvages, Maximilien ; Boisseau, Pierre ; Volot, Fabienne ; Rauch, Antoine ; Trossaërt, Marc ; Itzhar, Nathalie ; Goudemand, Jenny ; Lenting, Peter J ; Castet, Sabine ; Falaise, Céline ; Pan-Petesch, Brigitte ; Jeanpierre, Emmanuelle

BACKGROUNDType 2 Normandy von Willebrand disease (VWD2N) is usually perceived as a mild bleeding disorder that can be treated with desmopressin (DDAVP). However, VWD2N patients can be compound heterozygous or homozygous for different variants, with p.Arg854Gln (R854Q) being the most frequent causative one. There are limited data about the impact of 2N variants on VWD2N phenotype and DDAVP response.OBJECTIVESThis study aims to describe the phenotype of VWD2N, including DDAVP response, according to genotype.METHODSVWD2N patients with a complete genotype/phenotype characterization by the French reference center for VWD, including MCMDM-1VWD bleeding score, were eligible to be included in the study. Results of the DDAVP trial were also collected.RESULTSA total of 123 VWD2N patients from the French registry were included in this study. Results were stratified according to the presence (R854QPos, n = 114) or absence (R854QNeg, n = 9) of at least 1 R854Q allele. Three R854QPos subgroups were further individualized: patients homozygous (R854QHmz, n = 55), compound heterozygous for R854Q and a null allele (R854Q/3, n = 48), or compound heterozygous for R854Q and another 2N variant (R854Q/2N, n = 11).FVIIIC levels were significantly lower in R854QNeg and R854Q/3 patients compared with R854QHmz ones (P < .001 and P < .0001, respectively). R854QNeg patients were diagnosed earlier due to bleeding symptoms and had a higher bleeding score than R854QPos patients (P < .001). In DDAVP trial, FVIII:C survival was lower in VWD type 2N than in type 1 patients. R854QPos patients had a heterogeneous DDAVP response, which was best predicted by baseline FVIII:C level.CONCLUSIONThe heterogeneous genetic background of VWD2N drives different bleeding phenotypes and response patterns to DDAVP, underlining the clinical relevance of DDAVP trial to identify patients potentially eligible to alternative therapeutic options.

2024-09-01·Journal of Thrombosis and Haemostasis

Acquired von Willebrand syndrome during extracorporeal membrane oxygenation support: a comprehensive review of current evidence: communication from the ISTH SSC on perioperative and critical care thrombosis and hemostasis

Review

作者: Sullenger, Bruce A ; Helms, Julie ; Tanaka, Kenichi A ; Mazzeffi, Michael ; Levy, Jerrold H ; Maier, Cheryl L ; Connors, Jean M ; Steiner, Marie E ; Frere, Corinne

During extracorporeal membrane oxygenation (ECMO) support, the high shear stress in the ECMO circuit results in increased proteolysis of von Willebrand factor (VWF), loss of VWF high-molecular-weight multimers, and impaired ability to bind to platelets and collagen. These structural changes in VWF are consistent with acquired von Willebrand syndrome (AVWS) type 2A and may contribute to the bleeding diathesis frequently observed in ECMO patients. We performed a systematic review of all clinical studies evaluating the prevalence and associated outcomes of AVWS in ECMO patients. Our findings suggest that almost all ECMO patients develop partial or complete loss of VWF high-molecular-weight multimers within a few hours of device implantation. The AVWS persists as long as the patient is supported by ECMO. Weaning from ECMO rapidly and completely resolves the AVWS. Nevertheless, few studies have reported bleeding outcomes in ECMO patients with AVWS, and the extent to which AVWS contributes to the bleeding diathesis during ECMO support cannot be determined by current evidence. Data supporting the use of VWF concentrates to prevent bleeding complications in ECMO patients remain limited.

2024-09-01·Journal of Thrombosis and Haemostasis

Genetic Variants, Thrombocytopenia and Clinical Phenotype of type 2B von Willebrand Disease: a median 16-year follow-up study

Article

作者: van Galen, Karin P.M. ; Meijer, Karina ; Cnossen, Marjon H. ; van Galen, Karin P M ; van Heerde, Waander L ; Kruip, Marieke J H A ; Atiq, Ferdows ; van Kwawegen, Calvin B ; Endenburg, Dara ; van der Bom, Johanna G. ; Cnossen, Marjon H ; de Meris, Joke ; Eikenboom, Jeroen ; Leebeek, Frank W.G. ; Leebeek, Frank W G ; Schols, Saskia E M ; van Heerde, Waander L. ; van Kwawegen, Calvin B. ; Fijnvandraat, Karin ; Kruip, Marieke J.H.A. ; Schols, Saskia E.M. ; van der Bom, Johanna G

BACKGROUNDType 2B von Willebrand disease (VWD) is a bleeding disorder caused by gain-of-function variants in the VWF gene. The laboratory and clinical phenotype of type 2B VWD is heterogeneous.OBJECTIVESWe investigated associations between genotype and phenotype over a median of 16 years follow-up in a large cohort of well-characterized patients.METHODSWe included 64 genetically confirmed type 2B VWD patients from the national multicenter "Willebrand in the Netherlands" study and retrospectively collected clinical and laboratory data from electronic patient records. We analyzed associations between genotype and thrombocytopenia, bleeding phenotype, and events leading to endothelial activation and von Willebrand factor (VWF) secretion, including surgery, desmopressin administration, pregnancy, and delivery.RESULTSThrombocytopenia manifested in 67.2% of patients, with varying occurrences between genetic variants (p.Arg1306Trp: 75.0%, p.Arg1308Cys: 58.3%). The most important determinant of thrombocytopenia was the p.Arg1306Trp VWF variant (odds ratio, 25.1). Platelet counts strongly varied over time and were continuously <150 × 10⁹/L in 37.5% of patients with p.Arg1306Trp vs 8.3% in p.Arg1308Cys. In our analysis, endothelial activation was not an independent determinant (odds ratio, 1.3) for thrombocytopenia occurrence. No association was found between thrombocytopenia and cumulative bleeding scores or annual bleeding rates. Four women showed declining platelet counts in all full-term pregnancies (n = 8) during the third trimester with a sharp decrease in the week before delivery. Postpartum hemorrhage, defined as >500 mL estimated blood loss at delivery, occurred in 5 of 8 deliveries, despite prophylactic treatment with VWF concentrates.CONCLUSIONThis study reveals a strong association between VWF variant p.Arg1306Trp and thrombocytopenia in type 2B VWD patients.