Publications by authors named "Ferdows Atiq"
The molecular background of quantitative defects of von Willebrand factor.
J Thromb Haemost
November 2024
Article Synopsis
- The study investigates how patients with Von Willebrand disease (VWD) perceive the severity of their condition, highlighting a gap in understanding patient experiences alongside traditional lab measures.
- A nationwide survey in the Netherlands included 736 VWD patients, who reported their disease severity, bleeding scores, and quality of life through a questionnaire.
- Results show that self-reported severity aligns well with clinical classifications, and factors like type of VWD, bleeding severity, gender, treatment history, and specific lab values significantly influence patients' perception of their disease severity.
Article Synopsis
- Type 2B Von Willebrand disease (VWD) is a bleeding disorder linked to specific genetic variations in the VWF gene, and the study aimed to explore how these genetic differences affect clinical symptoms over a 16-year period in a cohort of 64 patients.
- The research found that 67.2% of patients experienced thrombocytopenia (low platelet counts), which was most significantly associated with the p.Arg1306Trp genetic variant, showing considerably lower platelet counts compared to another variant, p.Arg1308Cys.
- Additionally, while some patient pregnancies led to decreased platelet counts, postpartum hemorrhages occurred despite preventative treatment, highlighting the complex relationship between genetic factors and bleeding events in affected individuals.
Low von Willebrand factor-unraveling an enigma wrapped in a conundrum.
J Thromb Haemost
December 2024
Article Synopsis
- The 2021 guidelines recommend categorizing patients with von Willebrand factor levels between 30 to 50 IU/dL and increased bleeding tendencies as type 1 von Willebrand disease (VWD), which has sparked debate.
- Recent studies show that people with partial VWF deficiency can have symptoms that change with age, indicating that Low VWF is a subgroup of type 1 VWD.
- The article discusses challenges in diagnosing type 1 VWD and presents a new diagnostic algorithm focusing on patients with VWF levels of 30 to 50 IU/dL who have little to no bleeding history and limited exposure to significant bleeding risks.
Background: von Willebrand factor (VWF)-R1205H variant (Vicenza) results in markedly enhanced VWF clearance in humans that has been shown to be largely macrophage-mediated. However, the biological mechanisms underlying this enhanced clearance remain poorly understood.
Objectives: This study aimed to investigate the roles of (i) specific VWF domains and (ii) different macrophage receptors in regulating enhanced VWF-R1205H clearance.
Article Synopsis
- - Rondaptivon pegol (BT200) is a modified RNA aptamer that increases levels of von Willebrand factor (VWF) in the blood by interfering with its removal by the immune system, particularly macrophages.
- - The study shows that BT200 specifically binds to a crucial part of the VWF protein (the A1 domain), which helps prevent the VWF from being cleared too quickly by liver receptors (LRP1).
- - The findings suggest that targeting pathways that clear VWF from the body may be an effective new treatment strategy for conditions like von Willebrand disease and hemophilia A.
For many years, it has been known that von Willebrand factor (VWF) interacts with factor VIII, collagen, and platelets. In addition, the key roles played by VWF in regulating normal hemostasis have been well defined. However, accumulating recent evidence has shown that VWF can interact with a diverse array of other novel ligands.
View Article and Find Full Text PDFArticle Synopsis
- von Willebrand disease (VWD) is a bleeding disorder that happens when a protein called von Willebrand factor (VWF) is missing or doesn’t work right in the body.
- The study looked at how changes in the VWF gene affect the different types of VWF proteins found in the blood of patients, using advanced testing methods.
- The researchers found that there are many different versions of VWF proteins in patients, which can help understand how this disease works and how to better diagnose and treat it.
Article Synopsis
- There is ongoing debate about the definition of type 1 von Willebrand disease (VWD), with previous guidelines suggesting that VWF levels <30 IU/dL indicate type 1 VWD and levels between 30 to 50 IU/dL signify low VWF.
- A study combining data from two national cohorts found that while nearly half of type 1 VWD patients had VWF levels <30 IU/dL, a significant number showed increases to low or normal levels with age.
- The analysis indicates that low VWF is not a separate condition but part of the evolving phenotype of age-dependent type 1 VWD, suggesting a need to reconsider current classification criteria for the disease.
Previous studies have reported elevated von Willebrand factor (VWF) levels in patients with sickle cell disease (SCD) and demonstrated a key role for the VWF-ADAMTS13 axis in the pathobiology of SCD vaso-occlusion. Although blood transfusion is the gold standard for stroke prevention in SCD, the biological mechanisms underpinning its improved efficacy compared with hydroxycarbamide are not fully understood. We hypothesized that the improved efficacy of blood transfusion might relate to differences in VWF-ADAMTS13 axis dysfunction.
View Article and Find Full Text PDFDesmopressin testing in von Willebrand disease: Lowering the burden.
Res Pract Thromb Haemost
August 2022
Background: Individuals with von Willebrand disease (VWD) require desmopressin testing because of interindividual response differences. However, testing is burdensome, while not all patients may need extensive testing.
Objectives: To provide von Willebrand factor (VWF) cutoffs that predict desmopressin nonresponse and thereby identify individuals who do not need extensive testing in a retrospective cohort.
Article Synopsis
- Von Willebrand disease (VWD) is a bleeding disorder resulting from either low levels or dysfunctional von Willebrand factor (VWF), with different types categorized by severity and nature of the defect.
- Research focused on platelet factor 4 (PF4) among a large group of VWD patients revealed that lower PF4 levels were found in type 2B, and higher PF4 levels were linked to current bleeding occurrences, especially in type 1 VWD.
- The study suggests that the process of platelet degranulation and the release of their contents might influence bleeding symptoms across various VWD types.
Article Synopsis
- Genotyping is generally not done when diagnosing von Willebrand disease (VWD), leaving a gap in understanding the genetic causes and how they affect different patient phenotypes, particularly in type 1 VWD.
- A study analyzed the gene in 390 VWD patients, revealing that genetic variants were present in a majority of cases (61.5% for type 1, 98.4% for type 2, and 100% for type 3), with many novel variants identified.
- The research highlighted distinct clinical features between type 1 VWD patients with and without gene variants, indicating that understanding these genetic factors could significantly improve patient management and treatment approaches.
Patients with type 1 and type 2 von Willebrand disease (VWD) can be treated with desmopressin. Although a previous study has shown that the location of the causative VWF gene variant is associated with desmopressin response in type 1 VWD, the association between variants in the VWF gene and desmopressin response is not yet fully understood. Our primary aim was to compare desmopressin response in type 1 VWD patients with and without a VWF gene variant.
View Article and Find Full Text PDFArticle Synopsis
- The study investigates the social participation of patients with Von Willebrand disease (VWD) in the Netherlands, as previous research has primarily focused on haemophilia.
- It includes 788 VWD patients and analyzes various factors, including education levels and absenteeism from school or work, particularly noting that adult patients with type 3 VWD have lower educational attainment and higher absenteeism.
- The results indicate that severe bleeding episodes and certain demographics are linked to reduced social participation and increased occupational disability among VWD patients, highlighting specific challenges faced by those with the disease.
Background: An appropriate clinical diagnosis of von Willebrand disease (VWD) can be challenging because of a variable bleeding pattern and laboratory phenotype. Genotyping is a powerful diagnostic tool and may have an essential role in the diagnostic field of VWD.
Objectives: To unravel the clinical and laboratory heterogeneity of genetically confirmed VWD type 2M patients and to investigate their relationship.
Background: Platelets play a key role in hemostasis through plug formation and secretion of their granule contents at sites of endothelial injury. Defects in von Willebrand factor (VWF), a platelet α-granule protein, are implicated in von Willebrand disease (VWD), and may lead to defective platelet adhesion and/or aggregation. Studying VWF quantity and subcellular localization may help us better understand the pathophysiology of VWD.
View Article and Find Full Text PDFArticle Synopsis
- This study focuses on validating VWF multimer densitometric analysis for classifying von Willebrand disease (VWD), aiming to improve upon the existing visual analysis methods that are time-consuming and less accurate.
- Researchers analyzed blood samples from 560 VWD patients using Western blotting and IMAGEJ for detailed measurements of VWF multimer patterns, achieving high accuracy rates in distinguishing various VWD types and multimer conditions.
- Findings revealed that the medium-large VWF multimer index was not only reliable for classification but also showed a correlation with bleeding severity in type 1 VWD patients, suggesting it could enhance understanding of the disease's clinical features.
It is well known that high von Willebrand factor (VWF) and factor VIII (FVIII) levels are associated with an increased risk of cardiovascular disease. It is still debated whether VWF and FVIII are biomarkers of endothelial dysfunction and atherosclerosis or whether they have a direct causative role. Therefore, we aimed to unravel the pathophysiological pathways of increased VWF and FVIII levels associated with cardiovascular risk factors.
View Article and Find Full Text PDFBackground: Important diagnostic and clinical aspects of moderately reduced von Willebrand factor (VWF) levels are still unknown. There is no clear evidence which cutoff value (0.50 vs 0.
View Article and Find Full Text PDFBackground And Purpose: Silent cerebral infarcts (SCIs) are the most common neurological complication in children and adults with sickle cell disease (SCD). In this systematic review, we provide an overview of studies that have detected SCIs in patients with SCD by cerebral magnetic resonance imaging (MRI). We focus on the frequency of SCIs, the risk factors involved in their development and their clinical consequences.
View Article and Find Full Text PDFVon Willebrand disease (VWD) is the most common inherited bleeding disorder and is mainly caused by dominant-negative mutations in the multimeric protein von Willebrand factor (VWF). These mutations may either result in quantitative or qualitative defects in VWF. VWF is an endothelial protein that is secreted to the circulation upon endothelial activation.
View Article and Find Full Text PDFThe 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.
View Article and Find Full Text PDFVon Willebrand disease (VWD) is the most common inherited bleeding disorder. Most patients with mild and moderate VWD can be treated effectively with desmopressin. The management of severe VWD patients, mostly affected by type 2 and type 3 disease, can be challenging.
View Article and Find Full Text PDF