von Willebrand activation factor as a marker of mortality, cardiovascular events, and bleeding complications in patients treated with oral anticoagulants

Lind, Marcus; Johansson, Lars; Nilsson, Torbjörn; Jansson, Jan‐Håkan; Hollestelle, Martine J.

doi:10.1016/j.thromres.2015.08.016

Cited by 3 publications

(9 citation statements)

References 25 publications

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“…We have previously shown that this biomarker acts as an independent risk factor for adverse events, including cardiovascular events (stroke, acute coronary syndrome and acute heart failure), cardiovascular death, all cause mortality and major haemorrhagic episodes in a ‘real-life’ anticoagulated non-valvular AF population 25 . In another study, raised vWF activation factor levels (a modified test that detects vWF with high platelet affinity) correlated with all-cause mortality and cardiovascular events, but no association was observed with bleeding complications 37 . The same group had previously described an increased risk of bleeding complications, cardiovascular and all-cause mortality in patients with high levels of vWF during treatment with warfarin; nonetheless, only one third of the subjects in both studies had AF as the indication for OAC 38 .…”

Section: Discussionmentioning

confidence: 99%

Does von Willebrand factor improve the predictive ability of current risk stratification scores in patients with atrial fibrillation?

García-Fernández

Roldán

Rivera‐Caravaca

et al. 2017

Sci Rep

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Von Willebrand factor (vWF) is a biomarker of endothelial dysfunction. We investigated its role on prognosis in anticoagulated atrial fibrillation (AF) patients and determined whether its addition to clinical risk stratification schemes improved event-risk prediction. Consecutive outpatients with non-valvular AF were recruited and rates of thrombotic/cardiovascular events, major bleeding and mortality were recorded. The effect of vWF on prognosis was calculated using a Cox regression model. Improvements in predictive accuracy over current scores were determined by calculating the integrated discrimination improvement (IDI), net reclassification improvement (NRI), comparison of receiver-operator characteristic (ROC) curves and Decision Curve Analysis (DCA). 1215 patients (49% males, age 76 (71–81) years) were included. Follow-up was almost 7 years. Significant associations were found between vWF and cardiovascular events, stroke, mortality and bleeding. Based on IDI and NRI, addition of vWF to CHA2DS2-VASc statistically improved its predictive value, but c-indexes were not significantly different. For major bleeding, the addition of vWF to HAS-BLED improved the c-index but not IDI or NRI. DCA showed minimal net benefit. vWF acts as a simple prognostic biomarker in AF and, whilst its addition to current scores statistically improves prediction for some endpoints, absolute changes and impact on clinical decision-making are marginal.

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Section: Discussionmentioning

confidence: 99%

Does von Willebrand factor improve the predictive ability of current risk stratification scores in patients with atrial fibrillation?

García-Fernández

Roldán

Rivera‐Caravaca

et al. 2017

Sci Rep

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“…In patients with high levels of vWF activation and antigen, the incidence of cardiovascular events and mortality is especially high, indicating that these patients have an increased thrombotic risk. 25,32 An interesting finding is that patients without OAC seem to have substantially higher levels of vWF HMWMs. The larger multimeric forms of vWF are hemostatically more active, adhering better to endothelium and platelets.…”

Section: Discussionmentioning

confidence: 98%

“…24 Meanwhile, Roldán et al demonstrated that high plasma vWF levels are an independent risk factor for adverse events in anticoagulated patients with AF, 8 and Lind et al associated vWF factor with all-cause mortality and cardiovascular events in patients with AF. 25 Paradoxically, high levels of vWF antigen are associated with both thrombotic events and bleeding complications in patients treated with OACs. 8,26 The mechanism for the dual association is not clear, and different pathways could contribute to high levels of vWF.…”

Section: Discussionmentioning

confidence: 99%

“…21,29 Plasma levels of vWF antigen are somewhat reduced by OAC treatment. 23,25 As it is well known, vWF possesses several functions in hemostasis; among them, some of the most important might be protecting factor VIII from proteolysis or cellular uptake besides binding to the surface of activated platelets and endothelial cells. 5 Thrombin cleaves vWF off of FVIII, releasing it to mediate platelet adhesion and aggregation.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Von Willebrand Factor: Multimeric Structure and Functional Activity in Patients With Atrial Fibrillation With and Without Oral Anticoagulation

López-Castaneda

Valencia-Hernández

Arean

et al. 2017

Clin Appl Thromb Hemost

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von Willebrand factor (vWF) is a multimeric glycoprotein present in blood plasma. It is synthesized in megakaryocytes and endothelial cells, secreted into circulation in the form of high-molecular-weight multimers (HMWMs), and cleaved into shorter, less active multimers by ADAMTS13. It is essential for platelet adhesion and aggregation. Previous studies have investigated the relationship between vWF levels and thromboembolic events with little regard to vWF multimeric structure. Patients with atrial fibrillation (AF) exhibit higher plasma vWF and lower ADAMTS13 levels. One hundred seven patients with AF, 51 anticoagulated and 56 nonanticoagulated, were eligible for the study. Plasma samples were analyzed for vWF antigen, vWF activity, and ADAMTS13; vWF multimers were analyzed by Western blot in 1% to 1.3% sodium dodecyl sulfate agarose gel electrophoresis. Patients with AF without oral anticoagulation (OAC) had significantly higher vWF plasma levels (154.00 [75-201] UI/dL) and vWF activity (60.00% [20%-210%]) compared to patients with ] UI/dL, P ¼ <.001; 50.00% [20%-160%], P ¼ .02). Both were specially decreased in patients treated with acenocumarin. Patients without OAC also showed lower ADAMTS13 levels and presence of vWF HMWMs. Patients with AF show higher plasma levels and vWF activity. Moreover, treatment with traditional OAC (acenocumarin) significantly reduced vWF levels. Patients without OAC might have an increased risk of thrombotic events showing lower ADAMTS13 and higher vWF levels. Patients with stroke had higher plasma levels, vWF activity, and HMWMs. Our study suggests that increased vWF levels and presence of HMWMs could be related to cerebrovascular disease and may represent useful biomarkers for stroke in AF.

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Endothelial Dysfunction and Parenchymal Hematoma in Ischemic Stroke Patients after Endovascular Thrombectomy

et al. 2023

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Background and Purpose: Endothelial dysfunction (ED) may result in parenchymal injury and, therefore, worsen the outcomes of ischemic stroke. This study aimed to determine whether ED could predict parenchymal hematoma (PH) in ischemic stroke patients treated with endovascular thrombectomy (EVT). Methods: Patients with large artery occlusion in the anterior circulation and treated with EVT were prospectively enrolled from 2 stroke centers. Serum soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, soluble E-selectin, and von Willebrand factor (vWF) were tested and summed to a standardized score to reflect the levels of ED. PH was diagnosed according to the Heidelberg Bleeding Classification. Results: Of the 325 enrolled patients (mean age, 68.6 years; 207 men), 41 (12.6%) developed PH. Patients with PH had higher concentrations of soluble E-selectin, vWF, and ED sum score. After adjusting for demographic characteristics, National Institutes of Health Stroke Scale score, pre-treatment Alberta stroke program early computerized tomography score, and other potential confounders, the increased ED burden was associated with PH (odds ratio, 1.432; 95% confidence interval, 1.031−1.988; P=0.032). Similar significant results were found in the sensitivity analysis. The multiple-adjusted spline regression model showed a linear association between the total ED score and PH (P=0.001 for linearity). Adding ED score to the conventional model significantly improved the risk prediction of PH (net reclassification improvement=25.2%, P=0.001; integrated discrimination index=2.9%; P=0.001). Conclusions: This study demonstrated that ED might be related to PH. Introducing the ED score could increase the reliability of PH risk model for stroke patients treated with EVT.

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von Willebrand activation factor as a marker of mortality, cardiovascular events, and bleeding complications in patients treated with oral anticoagulants

Cited by 3 publications

References 25 publications

Does von Willebrand factor improve the predictive ability of current risk stratification scores in patients with atrial fibrillation?

Does von Willebrand factor improve the predictive ability of current risk stratification scores in patients with atrial fibrillation?

Von Willebrand Factor: Multimeric Structure and Functional Activity in Patients With Atrial Fibrillation With and Without Oral Anticoagulation

Endothelial Dysfunction and Parenchymal Hematoma in Ischemic Stroke Patients after Endovascular Thrombectomy

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