scholarly journals von Willebrand factor/ADAMTS13 ratio at presentation of acute ischemic brain injury is predictive of outcome

2020 ◽  
Vol 4 (2) ◽  
pp. 398-407 ◽  
Author(s):  
Alice Taylor ◽  
Chiara Vendramin ◽  
Deepak Singh ◽  
Martin M. Brown ◽  
Marie Scully
Keyword(s):  
Brain Injury ◽  
Von Willebrand Factor ◽  
Stroke Severity ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Mortality And Morbidity ◽  
Increased Risk ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Acute ischemic stroke (IS) and transient ischemic attack (TIA) are associated with raised von Willebrand factor (VWF) and decreased ADAMTS13 activity (ADAMTS13Ac). Their impact on mortality and morbidity is unclear. We conducted a prospective investigation of the VWF-ADAMTS13 axis in 292 adults (acute IS, n = 103; TIA, n = 80; controls, n = 109) serially from presentation until >6 weeks. The National Institutes of Health Stroke Score (NIHSS) and modified Rankin scale (mRS) were used to assess stroke severity. Presenting median VWF antigen (VWF:Ag)/ADAMTS13Ac ratios were: IS, 2.42 (range, 0.78-9.53); TIA, 1.89 (range, 0.41-8.14); and controls, 1.69 (range, 0.25-15.63). Longitudinally, the median VWF:Ag/ADAMTS13Ac ratio decreased (IS, 2.42 to 1.66; P = .0008; TIA, 1.89 to 0.65; P < .0001). The VWF:Ag/ADAMTS13Ac ratio was higher at presentation in IS patients who died (3.683 vs 2.014; P < .0001). A presenting VWF:Ag/ADAMTS13Ac ratio >2.6 predicted mortality (odds ratio, 6.33; range, 2.22-18.1). Those with a VWF:Ag/ADAMTS13Ac ratio in the highest quartile (>3.091) had 31% increased risk mortality. VWF:Ag/ADAMTS13Ac ratio at presentation of ischemic brain injury was associated with higher mRS (P = .021) and NIHSS scores (P = .029) at follow-up. Thrombolysis resulted in prompt reduction of the VWF:Ag/ADAMTS13Ac ratio and significant improvement in mRS on follow-up. A raised VWF:Ag/ADAMTS13Ac ratio at presentation of acute IS or TIA is associated with increased mortality and poorer functional outcome. A ratio of 2.6 seems to differentiate outcome. Prompt reduction in the ratio in thrombolysed patients was associated with decreased mortality and morbidity. The VWF:Ag/ADAMTS13Ac ratio is a biomarker for the acute impact of an ischemic event and longer-term outcome.

Combined effects of plasma von Willebrand factor and platelet measures on the risk of incident venous thromboembolism

Blood ◽  
2021 ◽  
Author(s):  
Magnus Sandvik Edvardsen ◽  
Ellen-Sofie Hansen ◽  
Kristian Hindberg ◽  
Vânia Maris Morelli ◽  
Thor Ueland ◽  
...  
Keyword(s):  
Platelet Count ◽  
Venous Thromboembolism ◽  
Von Willebrand Factor ◽  
Platelet Reactivity ◽  
High Plasma ◽  
Combined Effects ◽  
Exposure Group ◽  
Increased Risk ◽  
Von Willebrand ◽  
Willebrand Factor

Plasma von Willebrand factor (VWF) and platelet reactivity are both risk factors for venous thromboembolism (VTE), and VWF can promote hemostasis by interaction with platelets. In this study, we explored the combined effects of plasma VWF and platelet measures on the risk of incident VTE. A population-based nested case-control study with 403 cases and 816 controls was derived from the Tromsø Study. VWF, platelet count and mean platelet volume (MPV) were measured in blood samples drawn at baseline. Odds ratios (ORs) with 95% confidence intervals (CIs) for VTE were estimated across VWF tertiles, within predefined MPV (<8.5, 8.5-9.5, ≥9.5 fL) and platelet count (<230, 230-299, ≥300·109 L-1) strata. Here, participants with VWF levels in the highest tertile and MPV ≥9.5 fL had an OR of 1.98 (95% CI 1.17-3.36) for VTE compared with those in the lowest VWF tertile and with MPV <8.5 fL in the age- and sex-adjusted model. In the joint exposure group, 48% (95% CI 15% to 96%) of VTEs were attributable to the biological interaction between VWF and MPV. Similarly, individuals with VWF in the highest tertile and platelet count ≥300·109 L-1 had an OR of 2.91 (95% CI 1.49-5.67) compared with those with VWF in the lowest tertile and platelet count <230, and 39% (95% CI -2% to 97%) of VTEs in the joint exposure group were explained by the interaction. Our results suggest that both platelet reactivity and platelet count interact biologically with high plasma VWF, resulting in an increased risk of incident VTE.

Effect of the Antioxidants Selenium and Beta-carotene on HIV-related Endothelium Dysfunction

1998 ◽  
Vol 80 (12) ◽  
pp. 1015-1017 ◽  
Author(s):  
M. Seigneur ◽  
A. D. Blann ◽  
M. Renard ◽  
F. Resplandy ◽  
J. Amiral ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Von Willebrand Factor ◽  
Inflammatory Markers ◽  
Beta Carotene ◽  
Soluble Thrombomodulin ◽  
Endothelium Dysfunction ◽  
Increased Risk ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryPatients infected with HIV are at increased risk of atherosclerosis, and have evidence of endothelium dysfunction. The hypothesis was tested that HIV-related endothelium dysfunction is related to loss of antioxidants. This was done by the supplementation of the antioxidants selenium and beta-carotene. We supplemented the diet of 10 HIV-sero-positive subjects with 100 μg selenium daily, 11 subjects with 30 mg beta-carotene twice daily while 15 subjects were not supplemented. Plasma was obtained at outset and after a year, and tested by ELISA for endothelial cell, platelet and inflammatory markers.The non-supplemented patients experienced increases in von Wille-brand factor and soluble thrombomodulin (both p < 0.01). There were no changes in any of the indices in the patients taking selenium or beta-carotene.Increased von Willebrand factor and soluble thrombomodulin in the non-supplemented patients imply increased damage to the endothelium over the year of the study. Therefore we interpret the lack of increase in the patients taking antioxidants as evidence of the protection of the endothelium by these agents.

scholarly journals Cerebral Sinus and Venous Thrombosis Associated with von Willebrand Factor, Independently of Factor VIII

2008 ◽  
Vol 1 ◽  
pp. CCRep.S737
Author(s):  
Mari Terashima ◽  
Hiroshi Kataoka ◽  
Hirosei Horikawa ◽  
Hiroyuki Nakagawa ◽  
Toshiaki Taoka ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Factor Viii ◽  
Von Willebrand Factor ◽  
Transluminal Angioplasty ◽  
Right Hand ◽  
Increased Risk ◽  
Cerebral Sinus ◽  
The Right ◽  
Von Willebrand ◽  
Willebrand Factor

Background and purpose Previous studies have linked procoagulant factor VIII (F VIII) to an increased risk of venous thrombosis, whereas the relation between plasma von Willebrand factor (VWF) and venous thrombosis remains poorly understood. Elevated VWF levels are frequently found in patients with cerebral sinus and venous thrombosis (CSVT), always in association with high F VIII levels. We describe a patient with CSVT accompanied by elevated VWF levels without high F VIII levels. Case description A 23-year-old healthy man who had headache noticed difficulty in moving the right hand. On the following day, he lost consciousness and had partial seizures of the right hand. After regaining consciousness, weakness of the right extremities developed. The cranial angiogram confirmed occlusion of the superior sagittal sinus. The levels of VWF and F VIII were 238% and 101.9 IU/dl, respectively. We performed balloon percutaneous transluminal angioplasty and mechanical thrombectomy, leading to successful recanalization of the intracranial sinuses. VWF levels were decreased along with radiographic improvement, independently of F VIII. Conclusion VWF may contribute to CSVT and that inhibition of VWF activity potentially has a role in the future treatment of pathological conditions related to venous thrombosis.

scholarly journals ON THE VERSATILITY OF VON WILLEBRAND FACTOR

2013 ◽  
Vol 5 (1) ◽  
pp. e2013046 ◽  
Author(s):  
Antoine Rauch ◽  
Peter Lenting
Keyword(s):  
Structure Function ◽  
Von Willebrand Factor ◽  
Plasma Concentrations ◽  
Von Willebrand Disease ◽  
Physiological Relevance ◽  
Increased Risk ◽  
Inflammatory Processes ◽  
Thrombotic Complications ◽  
Von Willebrand ◽  
Willebrand Factor

Von Willebrand factor (VWF) is a large multimeric protein, the function of which has been demonstrated to be pivotal to the haemostatic system. Indeed, quantitative and/or qualitative abnormalities of VWF are associated with the bleeding disorder Von Willebrand disease (VWD). Moreover, increased plasma concentrations of VWF have been linked to an increased risk for thrombotic complications. In the previous decades, many studies have contributed to our understanding of how VWF is connected to the haemostatic system, particularly with regard to structure-function relationships. Interactive sites for important ligands of VWF (such as factor VIII, collagen, glycoprotein Iba, integrin aIIbb3 and protease ADAMTS13) have been identified, and mutagenesis studies have confirmed the physiological relevance of the interactions between VWF and these ligands.  However, we have also become aware that VWF has a more versatile character than previously thought, given its potential role in various non-hemostatic processes, like intimal thickening, tumor cell apoptosis and inflammatory processes. In the presence review, a summary of our knowledge on VWF structure-function relationships is provided in the context of the "classical" haemostatic task of VWF and in perspective of pathological processes beyond haemostasis.

Plasma von Willebrand Factor Levels Correlate with Clinical Outcome of Severe Traumatic Brain Injury

2007 ◽  
Vol 24 (8) ◽  
pp. 1331-1338 ◽  
Author(s):  
Clarissa Oliveira De Oliveira ◽  
Alexandre Gard Reimer ◽  
Adriana Brondani Da Rocha ◽  
Ivana Grivicich ◽  
Rogério Fett Schneider ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Clinical Outcome ◽  
Von Willebrand Factor ◽  
Severe Traumatic Brain Injury ◽  
Von Willebrand ◽  
Willebrand Factor

Carotid enlargement and serum levels of von Willebrand factor in rheumatoid arthritis: a follow-up study

2012 ◽  
Vol 31 (12) ◽  
pp. 1727-1732 ◽  
Author(s):  
Mirjana Veselinovic ◽  
Vladimir Jakovljevic ◽  
Aleksandra Jurisic-Skevin ◽  
Slavco Toncev ◽  
Dragan M. Djuric
Keyword(s):  
Rheumatoid Arthritis ◽  
Von Willebrand Factor ◽  
Serum Levels ◽  
Follow Up Study ◽  
Von Willebrand ◽  
Willebrand Factor

The A/T1381 polymorphism in the A1-domain of von Willebrand factor influences the affinity of von Willebrand factor for platelet glycoprotein Ibα

2007 ◽  
Vol 98 (07) ◽  
pp. 178-185 ◽  
Author(s):  
Tímea Szántó ◽  
Ágota Schlammadinger ◽  
Stephanie Staelens ◽  
Simon De Meyer ◽  
Kathleen Freson ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Association Studies ◽  
Platelet Glycoprotein ◽  
Platelet Receptor ◽  
Increased Risk ◽  
Static Conditions ◽  
A1 Domain ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryMany polymorphisms in vonWillebrand factor (VWF) have been reported and their association with VWF plasma levels or cardiovascular diseases has been investigated. The aim of this study was to examine whether the amino acid polymorphis mA/T1381 in the VWF A1-domain would affect VWF binding to platelet GPIbα. Sixty-one normal individuals were genotyped at the A/T1381 locus. Twenty-one A/A1381 homozygotes, 30 A/T1381 heterozygotes and 10 T/T1381 homozygotes were identified. Remarkably, when compared to VWF of A/T1381 and A/A1381 individuals, VWF of individuals carrying the T/T1381 variant showed an increased affinity for its platelet receptor GPIbα under static conditions, as reflected by an increased sensitivity to low concentrations of ristocetin or botrocetin. In addition, also the rVWF-T1381 demonstrated a higher affinity for GPIbα than rVWF-A1381. Interestingly, this enhanced affinity of the T/T variant over the A/T and A/A variant was, however, too subtle to affect platelet adhesion under physiological flow conditions, which fully corroborates the normal haemostatic phenotype of all individuals. We demonstrate that the VWF A/T1381 polymorphism plays an important role in inter-individual variability of the affinity of VWF for GPIbα, with T/T variants having a higher affinity than A/A and A/T variants, at least under static conditions in vitro. Further genetic linkage and association studies are necessary to establish whether the A/T1381 polymorphism could correlate with an increased risk of thrombotic events.

240 Course of von Willebrand Factor in Patients Supported with HeartWare HVAD in Mid-Term Follow-Up

2011 ◽  
Vol 30 (4) ◽  
pp. S85-S86
Author(s):  
N. Dranishnikov ◽  
A. Stepanenko ◽  
A. Frumkin ◽  
J. Vierecke ◽  
M. Schweiger ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Von Willebrand ◽  
Willebrand Factor

Inverse Regulation of Confluence-Dependent ADAMTS13 and von Willebrand Factor Expression in Human Endothelial Cells

2021 ◽  
Author(s):  
Miruna Popa ◽  
Markus Hecker ◽  
Andreas H. Wagner
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Von Willebrand Factor ◽  
Interleukin 10 ◽  
Endothelial Glycocalyx ◽  
Human Endothelial Cells ◽  
Proliferating Cells ◽  
Increased Risk ◽  
Von Willebrand ◽  
Willebrand Factor

AbstractADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) is a zinc-containing metalloprotease also known as von Willebrand factor (vWF)-cleaving protease. Low ADAMTS13 plasma levels are associated with an increased risk of arterial thrombosis, including myocardial infarction and cerebrovascular disease. The expression and regulation of this metalloprotease in human endothelial cells have not been systematically investigated. In this study, we demonstrate that ADAMTS13 expression is inhibited by proinflammatory cytokines tumor necrosis factor-α and interferon-γ as well as by CD40 ligand, which was hitherto unknown. Factors protecting against atherosclerosis such as exposure to continuous unidirectional shear stress, interleukin-10, or different HMG-CoA reductase inhibitors like, e.g., simvastatin, atorvastatin, or rosuvastatin, did not influence ADAMTS13 expression. Unidirectional periodic orbital shear stress, mimicking oscillatory flow conditions found at atherosclerosis-prone arterial bifurcations, had also no effect. In contrast, a reciprocal correlation between ADAMTS13 and vWF expression in endothelial cells depending on the differentiation state was noted. ADAMTS13 abundance significantly rose on both the mRNA and intracellular protein level and also tethered to the endothelial glycocalyx with the degree of confluency while vWF protein levels were highest in proliferating cells but significantly decreased upon reaching confluence. This finding could explain the anti-inflammatory and antithrombotic phenotype of dormant endothelial cells mediated by contact inhibition.

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