Towards novel treatment options in von Willebrand disease

Lenting, Peter J.; Kizlik-Manson, Claire; Casari, Caterina

doi:10.1111/hae.14518

Cited by 8 publications

(11 citation statements)

References 49 publications

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“…Nevertheless, the apparent neglect of this patient population has been recognized, and several new therapies are now under development. 46,66 Coincident with these advances to clinical care, further investigation continues into VWF biology, and in particular into a range of nonhemostatic functions that could be adversely affected in VWD. [67][68][69]…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, the pathophysiology of bleeding in VWD is complex and involves deficiency of the multimeric glycoprotein, VWF, as well as FVIII, in addition to multi-ple specific functional VWF defects (i.e., impaired platelet, collagen or FVIII binding). 45,46 This results in challenges designing and implementing treatments, as well as performing clinical trials to evaluate novel VWD therapies.…”

Section: New Treatment Options For Vwd: An Update 41 Introductionmentioning

confidence: 99%

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Diagnosis and treatment of von Willebrand disease in 2024 and beyond

James,

Leebeek,

Casari

et al. 2024

Haemophilia

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Manuscript Background and AimThe diagnosis and clinical care of patients with von Willebrand disease (VWD) has continued to evolve since the characterization of the von Willebrand factor (VWF) gene in 1985. This condition is almost certainly the most common inherited bleeding disorder, and the major symptomatic burden of the disease is experienced by females during their reproductive years. Diagnosis relies on the identification of a personal and family history of excessive mucocutaneous bleeding, and laboratory features consistent with quantitative and/or qualitative abnormalities of VWF. This review focuses on three aspects of VWD management, with current updates and a look into the future.Manuscript ThemesFirst, we will address the role of genetics in the diagnosis and possible therapies for VWD. With current technologies, VWD genetic diagnosis is usually confined to the confirmation of type 2 subtypes of the disease and type 3 VWD analysis for family planning. While type 3 VWD is a potential candidate for the application of gene therapy, no treatments are currently close to entering the clinic. Second, the peri‐procedural management of patients with VWD remains an important element of care. The choice of product, its dose and schedule all require careful consideration depending upon the type and disruptive nature of the planned procedure. Lastly, in addition to gene therapy, several other novel therapeutic interventions are also being developed for bleeding and prophylaxis in VWD. These include a VWF aptamer interfering with VWF clearance and bioengineered forms of VWF.

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Section: Discussionmentioning

confidence: 99%

Section: New Treatment Options For Vwd: An Update 41 Introductionmentioning

confidence: 99%

Diagnosis and treatment of von Willebrand disease in 2024 and beyond

James,

Leebeek,

Casari

et al. 2024

Haemophilia

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“…While it is already approved for hemophilia A patients by European Medicines Agency (EMA) and U.S. Food and Drug Administration (FDA), 55 there is still a need for more research in VWD patients. [56][57][58][59] Seminars in Thrombosis & Hemostasis © 2024. Thieme.…”

Section: Emicizumabmentioning

confidence: 99%

Progress in von Willebrand Disease Treatment: Evolution towards Newer Therapies

Moser,

Schoergenhofer,

Jilma

2024

Semin Thromb Hemost

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Abstractvon Willebrand disease (VWD) is a very heterogenous disease, resulting in different phenotypes and different degrees of bleeding severity. Established therapies (i.e., desmopressin, antifibrinolytic agents, hormone therapy for heavy menstrual bleeding, and von Willebrand factor [VWF] concentrates) may work in some subtypes, but not in all patients. In recent years, progress has been made in improving the diagnosis of VWD subtypes, allowing for more specific therapy. The impact of VWD on women's daily lives has also come to the fore in recent years, with hormone therapy, tranexamic acid, or recombinant VWF as treatment options. New treatment approaches, including the replacement of lacking factor VIII (FVIII) function, may work in those subgroups affected by severe FVIII deficiency. Reducing the clearance of VWF is an alternative treatment pathway; for example, rondaptivon pegol is a VWFA1 domain-binding aptamer which not only improves plasma VWF/FVIII levels, but also corrects platelet counts in thrombocytopenic type 2B VWD patients. These approaches are currently in clinical development, which will be the focus of this review. In addition, half-life extension methods are also important for the improvement of patients' quality of life. Targeting specific mutations may further lead to personalized treatments in the future. Finally, a few randomized controlled trials, although relatively small, have been published in recent years, aiming to achieve a higher level of evidence in future guidelines.

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“…False negatives were deemed more concerning because specific treatment approaches are needed for type 2 VWD (such as VWF concentrates rather than desmopressin) 5,7 . Desmopressin raises VWF levels by release of endothelial stores and can be effective in many type 1 VWD patients 25 . The treatment is less effective or even contraindicated in type 2 VWD because a functionally abnormal protein is released 9 .…”

Section: Von Willebrand Factor Testing Ratiosmentioning

confidence: 99%

“…5,7 Desmopressin raises VWF levels by release of endothelial stores and can be effective in many type 1 VWD patients. 25 The treatment is less effective or even contraindicated in type 2 VWD because a functionally abnormal protein is released. 9 A recently published meta-analysis also showed that using an activity/antigen ratio <0.7 versus a lower cutoff was more accurate for diagnosis of type 2 disease with a sensitivity of 0.90 and specificity of 0.91.…”

Section: Von Willebrand Disease Testing Backgroundmentioning

confidence: 99%

Von Willebrand factor testing ratios in the diagnosis and subtyping of von Willebrand disease

Smock

2023

Int J Lab Hematology

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Von Willebrand disease (VWD) is a common bleeding disorder of platelet adhesion with six currently recognized subtypes. Laboratory diagnosis consists of an initial test panel including antigen, activity and factor VIII measurements, sometimes followed by further specialized testing. VWF activity/antigen testing ratios help to differentiate type 1 and type 2 disease, which is important for selection of proper therapy. Recommended ratio cutoffs differ by guideline, ranging from 0.5 to 0.7, with 0.7 commonly recommended. The ratio cutoff used affects the sensitivity and specificity for type 2 diagnosis. Variability in VWD due to underlying mutations and patient factors, as well as variability in VWF tests, impact the accuracy of ratios for VWD subtyping. This review discusses the use of activity/antigen ratios in the diagnosis and subtyping of VWD with a focus on technical aspects of the tests.

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Towards novel treatment options in von Willebrand disease

Cited by 8 publications

References 49 publications

Diagnosis and treatment of von Willebrand disease in 2024 and beyond

Diagnosis and treatment of von Willebrand disease in 2024 and beyond

Progress in von Willebrand Disease Treatment: Evolution towards Newer Therapies

Von Willebrand factor testing ratios in the diagnosis and subtyping of von Willebrand disease

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