A 28-year-old woman was found to have coagulation factor Ⅷ activity (FⅧ∶C) <1% and von Willebrand factor antigen (VWF∶Ag) <1% during routine prenatal examinations. No pathogenic variation was found in the exon region of the VWF gene using next-generation sequencing. The clinical presentation of this patient does not match the clinical characteristics of type Ⅲ hemophilia [von Willebrand disease (VWD) ]; therefore, third-generation sequencing technology was used to perform whole-genome sequencing on the patient and her family members. Multiple members of the patient\'s paternal family carried a heterozygous variant of VPS33B, c.869G>C. The family members carrying this variant all had varying degrees of reduced VWF levels (39% -56% ). Moreover, the proband was detected with the heterozygous variant c.1474dupA in GP1BA. The ACMG and Clinvar databases determined that this variation was associated with platelet-type pseudo VWD. The decrease in VWF levels caused by heterozygous variations in VPS33B in families is the first international report, and no previous studies have reported cases of severe decrease in plasma VWF levels caused by double heterozygous variations in VPS33B and GP1BA.
一例28岁女性，孕期常规体检发现凝血因子Ⅷ活性（FⅧ∶C）<1%、血管性血友病因子抗原（VWF∶Ag）<1%。二代测序未发现其VWF基因外显子区域存在致病变异。由于该患者临床表现与Ⅲ型血管性血友病（VWD）临床特征不符，因此采用三代测序技术对该患者及其家系成员进行全基因组测序，发现该患者父系家族中有多位成员中携带VPS33B基因杂合变异c.869G>C，携带该变异的家系成员均有不同程度的VWF水平降低（39%～56%）。同时，先证者还检出GP1BA基因杂合变异c.1474dupA，ACMG及Clinvar数据库判断该变异与\"血小板型假性VWD\"相关。VPS33B基因杂合变异导致的VWF水平降低家系为国际首次报道，VPS33B基因与GP1BA基因双重杂合变异引起血浆VWF水平严重降低病例之前也未见报道。.

UNASSIGNED: Patient-reported outcomes measurement information system (PROMIS) measures can be used to measure patient-reported outcomes. PROMIS measures, including computer adaptive tests (CATs) and short forms, have demonstrated the ability to adequately assess outcomes in patients with hemophilia. It is, however, unclear if PROMIS measures are suitable for patients with von Willebrand disease (VWD), inherited platelet function disorders (IPFDs), and rare bleeding disorders (RBDs).
UNASSIGNED: To evaluate the feasibility, measurement properties, and relevance of PROMIS measures in adults with VWD, IPFDs, and RBDs.
UNASSIGNED: In this cross-sectional multicenter study, adults with VWD, IPFDs, and RBDs completed 9 PROMIS measures and the Short Form-36 version 2 (SF-36v2) electronically. Feasibility was determined by the number of completed items and floor/ceiling effects. Measurement properties included construct validity based on a multitrait-multimethod analysis and reliability using the reliability coefficient and greatest lower bound. Relevance was evaluated based on comparison with the Dutch general population.
UNASSIGNED: In total, 111 patients (median age, 57 years [IQR, 44-67]; 60% VWD, 16% IPFD, 24% RBD) participated. Mean number of items answered varied from 5.3 to 8.7 (range, 4-12) per PROMIS CAT in patients with VWD. Construct validity was supported for all CATs and all instruments had a good reliability (≥0.70). The PROMIS measures had less ceiling effects than the SF-36v2.
UNASSIGNED: The PROMIS measures are a feasible, valid, and reliable alternative for the SF-36v2 in patients with primarily nonsevere forms of VWD. The relevance of the selected measures was limited. Additional research is necessary to evaluate the PROMIS measures in adults with IPFDs and RBDs.

von Willebrand disease (VWD) is the most common inherited bleeding disorder. The disorder is characterized by excessive mucocutaneous bleeding. The most common bleeding manifestations of this condition include nosebleeds, bruising, bleeding from minor wounds, menorrhagia or postpartum bleeding in women as well as bleeding after surgery. Other less frequent symptoms include gastrointestinal bleeding, haematomas or haemarthroses. VWD pathophysiology is complex and results from defects in von Willebrand factor (VWF) glycoprotein. Quantitative deficiencies are responsible for type 1 VWD with a partial decrease of VWF and type 3 with the complete absence of VWF. Qualitative abnormalities cause type 2 VWD, being further divided into types 2A, 2B, 2M and 2N. Although common, VWD is at risk of misdiagnosis, overdiagnosis and underdiagnosis owing to several factors, including complex diagnosis, variability of bleeding symptoms, presence of external variables (blood groups and other physiological modifiers such as exercise, thyroid hormones, oestrogens, and ageing), and lack of disease awareness among non-specialist health-care providers. Establishing the correct VWD diagnosis requires an array of specialized phenotypic assays and/or molecular genetic testing of the VWF gene. The management of bleeding includes increasing endogenous VWF levels with desmopressin or infusion of exogenous VWF concentrates (plasma-derived or recombinant). Fibrinolytic inhibitors, topical haemostatic agents and hormonal therapies are used as effective adjunctive measures.

暂无摘要。

BACKGROUND: Von Willebrand Disease (VWD) is the most common inherited bleeding disorder. VWD is characterized by an abnormal quantity or quality of von Willebrand Factor (VWF). Anemia is often found at presentation for a bleeding disorder evaluation due to chronic blood loss.
OBJECTIVE: We hypothesized that anemia is associated with elevations in both VWF and factor VIII (FVIII) over baseline. We also hypothesized that obesity would be associated with increased levels of VWF.
METHODS: We conducted a single-center review of the electronic health record for patients that had proximal von Willebrand profiles and Hb data.
RESULTS: We identified 4552 unique subjects with VWF studies and a CBC within 24 h. We found that decreasing hemoglobin inversely correlated with VWF antigen, VWF ristocetin cofactor activity, and FVIII activity. We also found that obesity and Black race were independently associated with increased VWF antigen, activity, and FVIII activity. Hb, race, and body mass index (BMI) continued to be determinants of VWF and FVIII levels in multivariable analysis.
CONCLUSIONS: Our study demonstrates that anemia, race, and BMI were found to be associated with elevation of VWF antigen, VWF activity, and FVIII levels. As many individuals with anemia present for evaluation for a bleeding disorder, these variables need to be considered.
CONCLUSIONS: - Anemia was found to be associated with elevation of VWF antigen, VWF activity and FVIII levels. - Testing von Willebrand factor at times of anemia may mask a diagnosis of von Willebrand Disease.

UNASSIGNED: Various cardiovascular diseases cause acquired von Willebrand syndrome (AVWS), which is characterized by a decrease in high-molecular-weight (large) von Willebrand factor (VWF) multimers. Mitral regurgitation (MR) has been reported as a cause of AVWS. However, much remains unclear about AVWS associated with MR.
UNASSIGNED: To evaluate VWF multimers in MR patients and examine their impact on clinical characteristics.
UNASSIGNED: Moderate or severe MR patients (n = 84) were enrolled. VWF parameters such as the VWF large multimer index (VWF-LMI), a quantitative value that represents the amount of VWF large multimers, and clinical data were prospectively analyzed.
UNASSIGNED: At baseline, the mean hemoglobin level was 12.9 ± 1.9 g/dL and 58 patients (69.0%) showed loss of VWF large multimers defined as VWF-LMI < 80%. VWF-LMI in patients with degenerative MR was lower than in those with functional MR. VWF-LMI appeared to be restored the day after mitral valve intervention, and the improvement was maintained 1 month after the intervention. Seven patients (8.3%) had a history of bleeding, 6 (7.1%) of whom had gastrointestinal bleeding. Gastrointestinal endoscopy was performed in 23 patients (27.4%) to investigate overt gastrointestinal bleeding, anemia, etc. Angiodysplasia was detected in 2 of the 23 patients (8.7%).
UNASSIGNED: Moderate or severe MR is frequently associated with loss of VWF large multimers, and degenerative MR may cause more severe loss compared with functional MR. Mitral valve intervention corrects the loss of VWF large multimers. Gastrointestinal bleeding may be relatively less frequent and hemoglobin level remains stable in MR patients.

Von Willebrand disease (VWD) is the most common inherited bleeding disorder. It is primarily attributed to malfunctioning or deficient Von Willebrand factor (VWF). Thromboelastography (TEG) has emerged as a valuable tool for assessing coagulation dynamics and guiding transfusion therapy in bleeding patients. Given this, we present a case study of a 23-year-old pregnant female with a past medical history of type 2B VWD, wherein TEG was employed to optimize disease screening and therapy monitoring while minimizing costs and preventing complications associated with low platelet counts. This case underscores the potential utility of TEG in enhancing the care of VWD patients, particularly in unique critical settings such as pregnancy.

UNASSIGNED: Von Willebrand disease (VWD) is underdiagnosed, often delaying treatment. VWD claims coding is limited and includes no severity qualifiers; improved identification methods for VWD are needed. The aim of this study is to identify and characterize undiagnosed symptomatic persons with VWD in the US from medical insurance claims using predictive machine learning (ML) models.
UNASSIGNED: Diagnosed and potentially undiagnosed VWD cohorts were defined using Komodo longitudinal US claims data (January 2015-March 2020). ML models were built using key characteristics predictive of VWD diagnosis from the diagnosed cohort. Two ML models predicted VWD diagnosis with the highest accuracy in females (random forest; 84%) and males (gradient boosting machine; 85%). Undiagnosed persons suspected to have VWD were identified using an 80% cutoff probability; profiles of key characteristics were constructed.
UNASSIGNED: The trained ML models were applied to the undiagnosed cohort (28,463 females; 20,439 males) with suspected VWD. Fifty-two percent of undiagnosed females had heavy menstrual bleeding, a key pre-diagnosis symptom. Undiagnosed males tended to have more frequent medical procedures, hospitalizations, and emergency room visits compared with undiagnosed females.
UNASSIGNED: ML algorithms successfully identified potentially undiagnosed symptomatic people with VWD, although many may remain undiagnosed and undertreated. External validation of the algorithms is recommended.

A postpartum woman in her early 40s, with a history of pre-eclampsia and von Willebrand disease (VWD), presented to the emergency room with chest pain suggestive of an acute coronary syndrome. Initial workup revealed an evolving anterior wall ST-segment elevation myocardial infarction on ECG and elevated cardiac biomarkers, confirming myocardial damage. Point-of-care ultrasound showed apical hypokinesis and coronary angiography revealed a distal dissection of the left anterior descending coronary artery. There was TIMI 3 flow and no evidence of plaque rupture. No percutaneous coronary intervention was performed and the patient was managed conservatively.Fibromuscular dysplasia was ruled out on screening CT angiography. Dual antiplatelet therapy was initiated for an amended course of 3 months given the history of VWD. Our patient had an uncomplicated course in the hospital with a downward trend in their cardiac biomarkers, resolving anterior ST elevation on serial ECGs, and no bleeding complications.

von Willebrand disease (VWD) is the most frequent inherited bleeding disorder, with an estimated symptomatic prevalence of 1 per 1000 in the general population. VWD is characterized by defects in the quantity, quality, or multimeric structure of von Willebrand factor (VWF), a glycoprotein being hemostatically essential in circulation. VWD is classified into 3 principal types: low VWF/type 1 with partial quantitative deficiency of VWF, type 3 with virtual absence of VWF, and type 2 with functional abnormalities of VWF, being classified as 2A, 2B, 2M, and 2N. A new VWD type has been officially recognized by the ISTH SSC on von Willebrand factor which has also been discussed by the joint ASH/ISTH/NHF/WFH 2021 guidelines (ie, type 1C), indicating patients with quantitative deficiency due to an enhanced VWF clearance. With the advent of next-generation sequencing technologies, the process of genetic diagnosis has substantially changed and improved accuracy. Therefore, nowadays, patients with type 3 and severe type 1 VWD can benefit from genetic testing as much as type 2 VWD. Specifically, genetic testing can be used to confirm or differentiate a VWD diagnosis, as well as to provide genetic counseling. The focus of this manuscript is to discuss the current knowledge on VWD molecular pathophysiology and the application of genetic testing for VWD diagnosis.