Dataset Information

Elevated Plasma von Willebrand Factor Antigen and Activity Levels Are Associated With the Severity of Coronary Stenosis.

ABSTRACT: von Willebrand factor (VWF) acts as a bridge between platelets and the subendothelial matrix following vessel damage and plays a vital role in coronary artery disease (CAD). The aim of this study was to investigate the association between VWF and the severity of coronary stenosis quantified by the Gensini score in acute myocardial infarction (AMI), the most dangerous complication of CAD. Plasma VWF antigen (VWF: Ag) and VWF-collagen binding (VWF: CB) in normal controls (n = 123) and in patients with AMI (n = 205) were tested, and then the patients were divided based on Gensini scores. The levels of VWF: Ag and VWF: CB in patients with AMI were significantly higher than those in the control group (P < .001). Plasma levels of VWF: Ag and VWF: CB were positively correlated with both Gensini score and the number of affected vessels. Both VWF: Ag and VWF: CB were independent factors for coronary stenosis, adjusting confounding factors. Thus, the levels of VWF: Ag and VWF: CB were positively correlated with the severity of coronary stenosis. Screening of VWF at time of AMI may have prognostic value in terms of the severity of coronary stenosis.

SUBMITTER: Yan B

PROVIDER: S-EPMC7098204 | biostudies-literature | 2020 Jan-Dec

REPOSITORIES: biostudies-literature

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Elevated Plasma von Willebrand Factor Antigen and Activity Levels Are Associated With the Severity of Coronary Stenosis.

Yan Bin B Wang Qi Q Du Weipeng W Zhai Suping S Gou Chaoyang C Hu Tianxi T Xia Lijun L Ruan Changgeng C Zhao Yiming Y

Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis 20200101

von Willebrand factor (VWF) acts as a bridge between platelets and the subendothelial matrix following vessel damage and plays a vital role in coronary artery disease (CAD). The aim of this study was to investigate the association between VWF and the severity of coronary stenosis quantified by the Gensini score in acute myocardial infarction (AMI), the most dangerous complication of CAD. Plasma VWF antigen (VWF: Ag) and VWF-collagen binding (VWF: CB) in normal controls (n = 123) and in patients ...[more]

PMID: 31964151

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Project description:We correlated von Willebrand factor (VWF) activity indexes and brain natriuretic peptide (BNP) with measures of aortic stenosis (AS) severity, bleeding, symptoms, and freedom from death or aortic valve replacement. Patients with AS (n = 66 [16 mild, 20 moderate, and 30 severe]) and aortic valve replacement (n = 21) were assessed with VWF antigen, VWF latex agglutination immunoturbidic activity, platelet function analyzer collagen plus adenosine diphosphate (PFA-CADP), VWF multimer ratio, and BNP level after echocardiography. In patients with AS, the mean gradient correlated with BNP (Spearman r = 0.29, p = 0.02), VWF latex agglutination immunoturbidic activity/VWF antigen ratio (r = -0.41, p <0.001), PFA-CADP (r = 0.49, p <0.001), and VWF multimer ratio (r = -0.76, p <0.001). The area under the curve for detection of severe AS was 0.62 (95% confidence interval [CI] 0.48 to 0.77) by elevated BNP, 0.81 (95% CI 0.69 to 0.92) by PFA-CADP closure time, 0.69 (95% CI 0.55 to 0.82) by VWF latex agglutination immunoturbidic activity/VWF antigen ratio, and 0.86 (95% CI 0.76 to 0.95) by VWF multimer ratio. For the VWF multimer ratio, a threshold of 0.15 yielded a sensitivity and specificity for severe AS of 77% and positive predictive value of 74%. Bleeding (in 14%) was associated with a prolonged PFA-CADP time and reduced VWF latex agglutination immunoturbidic activity/VWF antigen ratio. Symptoms were associated with elevated BNP and low Duke Activity Status Index score. In 66 patients with AS, freedom from death (n = 4) or aortic valve replacement (n = 22) was associated with PFA-CADP (p = 0.003), VWF high-molecular-weight multimers (p = 0.009), and VWF latex agglutination immunoturbidic activity/VWF antigen ratio (p <0.001) but not BNP (p = 0.32). In severe AS versus aortic valve replacement, the PFA-CADP and VWF multimer ratio differed (p <0.001), but BNP and the VWF latex agglutination immunoturbidic activity/VWF antigen ratio did not. In conclusion, the VWF activity indexes were associated with AS severity and bleeding and were predictive of cardiovascular outcomes.

Project description:Essentials von Willebrand factor (VWF) is synthesized in endothelial cells and platelet precursors. Type 3 patients with Pro2808Leufs*24 have lower bleeding scores than other type 3s. The Pro2808Leufs*24 variant was examined in patient platelets and endothelial cells. Type 3s with this variant contain releaseable VWF, possibly reducing bleeding. SUMMARY:Background A novel variant, p.Pro2808Leufs*24, in the von Willebrand factor (VWF) gene was previously identified in the Canadian von Willebrand disease (VWD) patient population. Clinical observations of type 3 VWD patients with this variant indicate a milder bleeding phenotype compared with other type 3 patients. Objective To assess the effect of the Pro2808Leufs*24 variant on the molecular pathogenesis of VWD and correlate this with the phenotype observed in patients. Patients/Methods Phenotypic data from individuals in the Canadian type 3 VWD study were analyzed. VWF expression in platelets and plasma was assessed via immunoblotting. Cellular expression of VWF in platelets and blood outgrowth endothelial cells (BOEC) was examined via immunofluorescence microscopy and biochemical analysis in a type 3 index case and family member with Pro2808Leufs*24. Results Twenty-six individuals with the Pro2808Leufs*24 variant (16 type 3 VWD homozygous or compound heterozygous and 10 heterozygous family members) were studied. Bleeding scores were lower in type 3 patients with Pro2808Leufs*24 compared with type 3 patients with other variants, confirming a milder bleeding phenotype. Immunoblotting of platelet lysates detected VWF in the platelets of type 3 patients with Pro2808Leufs*24. Examination of an index case detected VWF within platelets via immunofluorescence microscopy, and in vitro experiments showed that this VWF was released upon platelet activation. Patient BOECs showed decreased VWF synthesis and secretion, although some VWF-containing granules were observed. Conclusion Type 3 VWD patients with the Pro2808Leufs*24 have bioavailable platelet-derived VWF that may produce a milder bleeding phenotype than other type 3s.

Project description:Introduction:Plasma factor VIII (FVIII) and von Willebrand factor (VWF) levels have been associated with the rate and severity of arterial thrombus formation and have been linked to outcomes following thrombolytic therapy in acute myocardial infarction patients. Here, we aimed to investigate FVIII and VWF levels during the course of thrombolysis in acute ischemic stroke (AIS) patients and to find out whether they predict long-term outcomes. Materials and methods:Study population included 131 consecutive AIS patients (median age: 69?years, 60.3% men) who underwent i.v. thrombolysis with recombinant tissue plasminogen activator (rt-PA). Blood samples were taken on admission, 1 and 24?h after rt-PA administration to measure FVIII activity and VWF antigen levels. Neurological deficit of patients was determined according to the National Institutes of Health Stroke Scale (NIHSS). ASPECT scores were assessed using computer tomography images taken before and 24?h after thrombolysis. Intracranial hemorrhage was classified according to the European Cooperative Acute Stroke Study (ECASS) II criteria. Long-term functional outcome was determined at 90?days after the event by the modified Rankin scale (mRS). Results:VWF levels on admission were significantly elevated in case of more severe AIS [median and IQR values: NIHSS <6:189.6% (151.9-233.2%); NIHSS 6-16: 199.6% (176.4-250.8%); NIHSS >16: 247.8% (199.9-353.8%), p?=?0.013]; similar, but non-significant trend was observed for FVIII levels. FVIII and VWF levels correlated well on admission (r?=?0.748, p?<?0.001) but no significant correlation was found immediately after thrombolysis (r?=?0.093, p?=?0.299), most probably due to plasmin-mediated FVIII degradation. VWF levels at all investigated occasions and FVIII activity before and 24?h after thrombolysis were associated with worse 24?h post-lysis ASPECT scores. In a binary backward logistic regression analysis including age, gender, high-sensitivity C-reactive protein, active smoking, diabetes, and NIHSS >5 on admission, elevated FVIII and VWF levels after thrombolysis were independently associated with poor functional outcomes (mRS???3) at 90?days (immediately after thrombolysis: FVIII: OR: 7.10, 95% CI: 1.77-28.38, p?=?0.006, VWF: OR: 6.31, 95% CI: 1.83-21.73, p?=?0.003; 24?h after thrombolysis: FVIII: OR: 4.67, 95% CI: 1.42-15.38, p?=?0.011, VWF: OR: 19.02, 95% CI: 1.94-186.99, p?=?0.012). Conclusion:Elevated FVIII activity and VWF antigen levels immediately after lysis and at 24?h post-therapy were shown to have independent prognostic values regarding poor functional outcomes at 90?days.

Dataset Information

Elevated Plasma von Willebrand Factor Antigen and Activity Levels Are Associated With the Severity of Coronary Stenosis.

Publications

Elevated Plasma von Willebrand Factor Antigen and Activity Levels Are Associated With the Severity of Coronary Stenosis.

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