von Willebrand factor propeptide and the occurrence of a first ischemic stroke

Schie, Marianne C. van; Maat, Moniek P.M. de; Dippel, Diederik W.J.; Groot, Philip G. de; Lenting, Peter J.; Leebeek, Frank W.G.; Hollestelle, Martine J.

doi:10.1111/j.1538-7836.2010.03863.x

Cited by 21 publications

(18 citation statements)

References 11 publications

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“…Interestingly, there is one recent study in which both VWF antigen and VWF propeptide were investigated in two casecontrol samples of patients with IS or transient ischemic attacks (n = 204 and n = 342) [11]. The results suggest that increased von Willebrand factor in ischemic stroke subtypes 279 secretion of VWF from the endothelium is an important mechanism underlying the association between total VWF levels and IS, but a lower clearance of VWF may also contribute.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, blood sampling was standardized and performed at two time points, whereof one was in the chronic phase. Only a few previous studies [5][6][7]11,17] have examined VWF levels at more than one well-defined time-point. There are also some limitations that should be considered.…”

Section: Discussionmentioning

confidence: 99%

“…There are fewer studies on VWF in IS, although increased levels of VWF have been reported in some case-control studies [5][6][7][8][9][10][11]. Furthermore, high plasma levels of VWF have been identified as a predictor of stroke in three prospective studies of subjects with and without atrial fibrillation [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

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Plasma levels of von Willebrand factor in the etiologic subtypes of ischemic stroke

Hanson

Jood

Karlsson

et al. 2011

Journal of Thrombosis and Haemostasis

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Summary. Background: Compared with coronary artery disease, there are few studies on von Willebrand factor (VWF) in ischemic stroke (IS). Moreover, there is little information on VWF in the etiologic subtypes of IS. Objectives: The aim of the present study was to investigate VWF in IS and in the etiologic subtypes of IS. Patients/methods: The Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS) is a case-control study comprising 600 patients and 600 matched controls. Etiologic IS subtype was defined according to the TOAST criteria. Blood sampling was performed in the acute phase and after 3 months. Results: The levels of VWF were increased in overall IS, at both time-points. The 3-month VWF levels were increased in the subtypes of large-vessel disease (LVD), cardioembolic (CE) stroke and cryptogenic stroke, but not in the subtype of smallvessel disease (SVD), as compared with the controls. The acute phase VWF levels were significantly increased in all four subtypes. In the multivariate regression analysis, with vascular risk factors as covariates, the 3-month VWF levels were associated with CE stroke and cryptogenic stroke, and the acute phase VWF levels with all subtypes. There were significant subtype-specific differences in VWF, with the highest levels in LVD and CE stroke. Conclusions: The present results show that VWF levels are increased in patients with IS. Furthermore, the VWF levels differ between etiologic IS subtypes and thus, it is important to consider etiologic subtypes in future studies of VWF in patients with IS.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Plasma levels of von Willebrand factor in the etiologic subtypes of ischemic stroke

Hanson

Jood

Karlsson

et al. 2011

Journal of Thrombosis and Haemostasis

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“…75 Endothelial activation, as indicated by an elevated VWFpp level has been implicated in chronic renal failure, aortic stenosis, ischemic stroke, sepsis, meningococcal disease, dengue, systemic sclerosis, sickle cell disease, HELLP syndrome, and asthma. [78][79][80][81][82][83][84][85][86] In addition to utility in identifying endothelial activation, VWFpp and VWF may also be used in a similar manner to identify platelet activation. 87 In some clinical circumstances, an elevated VWFpp level may indicate activation of both platelets and endothelial cells.…”

Section: Assay Of Plasma Vwfpp: Clinical Utility Vascular Disorders Amentioning

confidence: 99%

von Willebrand factor propeptide: biology and clinical utility

Haberichter

2015

Blood

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von Willebrand factor (VWF) is a large multimeric glycoprotein that mediates the attachment of platelets to damaged endothelium and also serves as the carrier protein for coagulation factor VIII (FVIII), protecting it from proteolytic degradation. Quantitative or qualitative defects in VWF result in von Willebrand disease (VWD), a common inherited bleeding disorder. VWF is synthesized with a very large propeptide (VWFpp) that is critical for intracellular processing of VWF. VWFpp actively participates in the process of VWF multimerization and is essential for trafficking of VWF to the regulated storage pathway. Mutations identified within VWFpp in VWD patients are associated with altered VWF structure and function. The assay of plasma VWFpp has clinical utility in assessing acute and chronic vascular perturbation associated with diseases such as thrombotic thrombocytopenic purpura, sepsis, and diabetes among others. VWFpp assay also has clear utility in the diagnosis of VWD subtypes, particularly in discriminating true type 3 subjects from type 1C (reduced plasma survival of VWF), which is clinically important and has implications for therapeutic treatment.

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“…It is also considered as an emerging target in cerebral ischaemia (Varga-Szabo et al, 2008;De Meyer et al, 2012). Investigations of independent case-control studies indicated the association between high vWF levels and the occurrence of a first ischaemic stroke and mortality in humans (Van Schie et al, 2010). Protection of vWF-deficient mice from ischaemic stroke injury (Kleinschnitz et al, 2009), together with enlarged infarct size in ADAMTS13-deficient mice (Fujioka et al, 2010;Khan et al, 2012), suggests an important role of vWF in ischaemic stroke.…”

Section: Figurementioning

confidence: 99%

A novel snake venom‐derived GPIb antagonist, anfibatide, protects mice from acute experimental ischaemic stroke and reperfusion injury

Fan

Hou

et al. 2015

British J Pharmacology

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Background and Purpose Ischaemic stroke is a serious disease with limited therapy options. Glycoprotein (GP)Ib binding to von Willebrand factor (vWF) exposed at vascular injury initiates platelet adhesion and contributes to platelet aggregation. GPIb has been suggested as an effective target for antithrombotic therapy in stroke. Anfibatide is a GPIb antagonist derived from snake venom and we investigated its protective effect on experimental brain ischaemia in mice. Experimental Approach Focal cerebral ischaemia was induced by 90 min of transient middle cerebral artery occlusion (MCAO). These mice were then treated with anfibatide (4, 2, 1 μg·kg−1), injected i.v., after 90 min of MCAO, followed by 1 h of reperfusion. Tirofiban, a GPIIb/IIIα antagonist, was used as a positive control. Key Results Twenty‐four hours after MCAO, anfibatide‐treated mice showed significantly improved ischaemic lesions in a dose‐dependent manner. The mice had smaller infarct volumes, less severe neurological deficits and histopathology of cerebrum tissues compared with the untreated MCAO mice. Moreover, anfibatide decreased the amount of GPIbα, vWF and accumulation of fibrin(ogen) in the vasculature of the ischaemic hemisphere. Tirofiban had similar effects on infarct size and fibrin(ogen) deposition compared with the MCAO group. Importantly, the anfibatide‐treated mice showed a lower incidence of intracerebral haemorrhage and shorter tail bleeding time compared with the tirofiban‐treated mice. Conclusions and Implications Our data indicate anfibatide is a safe GPIb antagonist that exerts a protective effect on cerebral ischaemia and reperfusion injury. Anfibatide is a promising candidate that could be beneficial for the treatment of ischaemic stroke.

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von Willebrand factor propeptide and the occurrence of a first ischemic stroke

Abstract: von Willebrand factor propeptide and the occurrence of a first ischemic stroke propeptide and the occurrence of a first ischemic stroke.

Cited by 21 publications

References 11 publications

Plasma levels of von Willebrand factor in the etiologic subtypes of ischemic stroke

Plasma levels of von Willebrand factor in the etiologic subtypes of ischemic stroke

von Willebrand factor propeptide: biology and clinical utility

A novel snake venom‐derived GPIb antagonist, anfibatide, protects mice from acute experimental ischaemic stroke and reperfusion injury

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