How I manage severe von Willebrand disease

Leebeek, Frank W.G.; Atiq, Ferdows

doi:10.1111/bjh.16186

Cited by 32 publications

(78 citation statements)

References 103 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Type 2 VWD, which affects about 20% of VWD patients, is characterized by an abnormal function of VWF. Type 3 VWD, the most severe form of VWD, affecting less than 5% of patients, is characterized by the absence of VWF [ 1 , 3 ]. Type 1 and 2 VWD usually have an autosomal dominant inheritance pattern, whereas type 3 VWD is an autosomal recessive disorder.…”

Section: Introductionmentioning

confidence: 99%

Major differences in clinical presentation, diagnosis and management of men and women with autosomal inherited bleeding disorders

et al. 2021

Self Cite

View full text Add to dashboard Cite

Background In recent years, more awareness is raised about sex-specific dilemmas in inherited bleeding disorders. However, no large studies have been performed to assess differences in diagnosis, bleeding phenotype and management of men and women with bleeding disorders. Therefore, we investigated sex differences in a large cohort of well-defined patients with autosomal inherited bleeding disorders (von Willebrand disease (VWD), rare bleeding disorders (RBDs) and congenital platelet defects (CPDs)). Methods We included patients from three nationwide cross-sectional studies on VWD, RBDs and CPDs in the Netherlands, respectively the WiN, RBiN and TiN study. In all studies a bleeding score (BS) was obtained, and patients filled in an extensive questionnaire on the management and burden of their disorder. Findings We included 1092 patients (834 VWD; 196 RBD; 62 CPD), of whom 665 (60.9%) were women. Women were more often referred because of a bleeding diathesis than men (47.9% vs 36.6%, p = 0.002). Age of first bleeding was similar between men and women, respectively 8.9 ± 13.6 (mean ±sd) years and 10.6 ± 11.3 years ( p = 0.075). However, the diagnostic delay, which was defined as time from first bleeding to diagnosis, was longer in women (11.6 ± 16.4 years) than men (7.7 ± 16.6 years, p = 0.002). Similar results were found when patients referred for bleeding were analyzed separately. Of women aging 12 years or older, 469 (77.1%) had received treatment because of sex-specific bleeding. Interpretation Women with autosomal inherited bleeding disorders are more often referred for bleeding, have a longer diagnostic delay, and often require treatment because of sex-specific bleeding. Funding The WiN study was supported (in part) by research funding from the Dutch Hemophilia Foundation (Stichting Haemophilia), Shire (Takeda), and CSL Behring (unrestricted grant).

show abstract

Section: Introductionmentioning

confidence: 99%

Major differences in clinical presentation, diagnosis and management of men and women with autosomal inherited bleeding disorders

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…[1][2][3][4] Patients with type 1 VWD have reduced von Willebrand factor (VWF) levels, whereas patients with type 2 VWD have an abnormal function of VWF, and patients with type 3 VWD have an absence of VWF. 1,5,6 The bleeding phenotype of patients with type 1 VWD is very heterogeneous. 1 Some determinants that are associated with the bleeding phenotype of type 1 VWD patients are age, sex, VWF and FVIII levels, presence of comorbidities, body mass index (BMI), VWF gene mutations, and some single-nucleotide polymorphisms outside the VWF gene.…”

Section: Introductionmentioning

confidence: 99%

von Willebrand factor and factor VIII levels after desmopressin are associated with bleeding phenotype in type 1 VWD

et al. 2019

Self Cite

View full text Add to dashboard Cite

Key Points• VWF and FVIII levels after desmopressin, which mimic hemostatic response, are associated with the bleeding phenotype of type 1 VWD patients.• Variability in VWF and FVIII response to hemostatic challenges may partly explain heterogeneity in bleeding phenotype of VWD patients.The bleeding phenotype of patients with type 1 von Willebrand disease (VWD) is very heterogeneous. We hypothesized that this heterogeneity may partly be explained by variability in response of von Willebrand factor (VWF) and factor VIII (FVIII) levels to stress during hemostatic challenges. We therefore investigated whether VWF and FVIII levels after administration of desmopressin, which mimic in vivo hemostatic response during hemostatic challenges, explain the heterogeneity in bleeding phenotype of patients with type 1 VWD. We performed a retrospective cohort study in 122 patients with type 1 VWD. All patients received a test dose of desmopressin shortly after diagnosis. Patients' mean age was 47 6 14 years, and the mean Tosetto bleeding score was 10 6 7. Higher FVIII activity during the complete time course after desmopressin administration (1, 3, and 5-6 hours), and higher VWF and FVIII levels combined at 3 hours after desmopressin administration, were associated with a lower bleeding score: b 5 -0.9 (-1.7; 20.1) and b 5 -1.2 (-1.9; 20.5), respectively, adjusted for age, sex, body mass index (BMI), and comorbidities. Patients with FVIII activity in the highest quartile 3 hours after desmopressin administration had a much lower bleeding score compared with patients in the other 3 quartiles (b 5 -5.1 [-8.2; 22.0]) and also had a lower chance of an abnormal bleeding score (odds ratio 5 0.2 [0.1-0.5]), both adjusted for age, sex, BMI, and comorbidities. In conclusion, VWF and FVIII levels after desmopressin administration, which mimic hemostatic response to hemostatic challenges, are associated with the bleeding phenotype of patients with type 1 VWD. This may partly explain the variability in bleeding phenotype of these patients.

show abstract

“… 2 , 3 Consequently, VWD patients also have reduced FVIII levels, contributing to their hypocoagulable state. 1 , 4 …”

Section: Introductionmentioning

confidence: 99%

“…It may also have important therapeutic consequences, for instance, in distinguishing type 2A and 2B from other type 2 VWD subtypes, since desmopressin that is used as treatment for many VWD patients is contraindicated in type 2B patients. 4 …”

Section: Introductionmentioning

confidence: 99%

Von Willebrand Factor Multimer Densitometric Analysis: Validation of the Clinical Accuracy and Clinical Implications in Von Willebrand Disease

et al. 2021

Self Cite

View full text Add to dashboard Cite

Von Willebrand factor (VWF) multimer analysis is important in the classification of von Willebrand disease (VWD). Current visual VWF multimer analysis is time consuming and inaccurate in detecting subtle changes in multimer patterns. Although VWF multimer densitometric analysis may be useful, the accuracy needs further investigation before it can be widely applied. In this study we aimed to validate VWF multimer densitometric analysis in a large cohort of VWD patients and to identify patient characteristics associated with densitometric outcomes. Patients were included from the Willebrand in the Netherlands (WiN) study, in which a bleeding score (BS) was obtained, and blood was drawn. For multimer analysis, citrated blood was separated on an agarose gel and visualized by Western blotting. IMAGEJ was used to generate densitometric images and medium-large VWF multimer index was calculated. We included 560 VWD patients: 328 type 1, 211 type 2, and 21 type 3 patients. Medium-large VWF multimer index performed excellent in distinguishing visually classified normal VWF multimers from reduced high-molecular-weight (HMW) multimers (area under the curve [AUC]: 0.96 [0.94-0.98], P < 0.001), normal multimers from absence of HMW multimers (AUC 1.00 [1.00-1.00], P < 0.001), and type 2A and 2B from type 2M and 2N (AUC: 0.96 [0.94-0.99], P < 0.001). Additionally, higher medium-large VWF multimer index was associated with lower BS in type 1 VWD: β = -7.6 (-13.0 to -2.1), P = 0.007, adjusted for confounders. Densitometric analysis of VWF multimers had an excellent accuracy compared with visual multimer analysis and may contribute to a better understanding of the clinical features such as the bleeding phenotype of VWD patients.

show abstract

How I manage severe von Willebrand disease

Cited by 32 publications

References 103 publications

Major differences in clinical presentation, diagnosis and management of men and women with autosomal inherited bleeding disorders

Major differences in clinical presentation, diagnosis and management of men and women with autosomal inherited bleeding disorders

von Willebrand factor and factor VIII levels after desmopressin are associated with bleeding phenotype in type 1 VWD

Von Willebrand Factor Multimer Densitometric Analysis: Validation of the Clinical Accuracy and Clinical Implications in Von Willebrand Disease

Contact Info

Product

Resources

About