Prospective Study on Soluble Thrombomodulin and von Willebrand Factor and the Risk of Ischemic and Hemorrhagic Stroke

Johansson, Lars; Jansson, Jan‐Håkan; Boman, Kurt; Nilsson, Torbjörn; Stegmayr, Birgitta; Hallmans, Göran

doi:10.1055/s-0037-1612975

Cited by 18 publications

(21 citation statements)

References 29 publications

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“…The vWF was shown to be predictive of stroke in the Rotterdam and Atherosclerosis Risk in Communities (ARIC) studies, 9,10 but others have reported no independent association between vWF and stroke [11][12][13][14] ; however, many of these studies were based on smaller participant numbers. Our results, generated in a more homogenous population of predominantly white men, provide additional support for an independent association between vWF and stroke that is not explained by inflammation.…”

Section: Discussionmentioning

confidence: 99%

“…4 The von Willebrand factor (vWF) is synthesized primarily by vascular endothelial cells and promotes platelet adhesion and aggregation, leading to thrombus formation. 1 Increased levels of vWF in stroke patients have been reported in several case-control studies, [5][6][7][8] but prospective studies have been inconsistent, with some showing a positive relationship 9,10 and others showing no relationship [11][12][13][14] between vWF and stroke risk. Fibrin D-dimer is the primary degradation product of cross-linked fibrin and is a marker of activated coagulation and fibrinolysis.…”

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confidence: 99%

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Fibrin D-Dimer, Tissue-Type Plasminogen Activator, von Willebrand Factor, and Risk of Incident Stroke in Older Men

Wannamethee¹,

Whincup²,

Lennon³

et al. 2012

Stroke

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Background and Purposes-Abnormalities in blood coagulation and the fibrinolytic system have been associated with increased risk of stroke, but few prospective studies have studied the associations in older adults. We have examined the associations between fibrin D-dimer, tissue-type plasminogen activator, and von Willebrand factor (vWF) and risk of stroke in older men and examined their predictive roles separately in normotensive and hypertensive men. Methods-Prospective study of 3358 men aged 60 to 79 years with no previous diagnosis of myocardial infarction or stroke and without atrial fibrillation followed-up for an average of 9 years, during which there were 187 incident stroke events. Results-Increased levels of D-dimer and vWF were associated with significantly increased risk of major stroke events after adjustment for potential confounders, including systolic blood pressure (adjusted hazard ratios and 95% confidence interval per standard deviation increase in D-dimer and vWF were 1.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Fibrin D-Dimer, Tissue-Type Plasminogen Activator, von Willebrand Factor, and Risk of Incident Stroke in Older Men

Wannamethee¹,

Whincup²,

Lennon³

et al. 2012

Stroke

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“…In the multivariate analysis, we found a positive independent association between tPA/PAI-1 complex and ICH and an inverse independent association between sTM and ICH. 4,5 The primary aim of the present prospective study was to test the hypothesis that concentrations of tPA/PAI-1 complex, tPA, PAI-1, sTM, and von Willebrand factor (VWF) were associated with hemorrhagic stroke in a study population without previous stroke, myocardial infarction, or cancer. Furthermore, a secondary objective was to investigate the relationship and possible interactions between tPA/PAI-1 complex, tPA, PAI-1, sTM, VWF, and cardiovascular risk factors and the risk for ICH in this study population.…”

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confidence: 99%

Hemostatic Factors as Risk Markers for Intracerebral Hemorrhage

Johansson

Jansson²,

Stegmayr³

et al. 2004

Stroke

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“…[24][25][26] Although many reports showed decreased platelet adhesion under flow conditions when plasma VWF was genetically deficient or inhibited by antibodies, 10,12,38,39 platelet adhesion and aggregation under flow conditions in the presence of higher concentration of VWF have not received much attention. In the present study, we analyzed platelet adhesion to an immobilized-collagen surface under flow using blood containing an extra amount of VWF, compared with the physiologic amount in normal blood.…”

Section: Discussionmentioning

confidence: 99%

“…[24][25][26] Those reports suggested that high level of FVIII or VWF in blood might have an ability to increase the hemostatic potential in patients with bleeding episodes caused by a defect in blood coagulation or thrombocytopenia. The vasopressin agonist desmopressin (DDAVP) is known to be an inducer of VWF release from endothelial cells and is used to control the bleeding of mild hemophilia and von Willebrand disease (VWD).…”

Section: Introductionmentioning

confidence: 99%

Von Willebrand factor accelerates platelet adhesion and thrombus formation on a collagen surface in platelet-reduced blood under flow conditions

Tomokiyo

Kamikubo

Hanada

et al. 2005

Blood

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Plasma von Willebrand factor (VWF) has been identified as an indispensable factor for platelet adhesion and thrombus formation on a collagen surface under flow conditions. VWF binds to collagen and then tethers platelets to the collagen surface through interaction with platelet glycoprotein Ib and also contributes to the thrombus formation on the collagen surface. In the present study, we demonstrated that the addition of VWF/factor VIII complex or purified VWF (> 2 ristocetin cofactor activity units/mL) increased platelet adhesion to the collagen surface in platelet-reduced blood (ϳ 5 ؋ 10 4 platelets/L) to the normal level. VWF had no stimulatory effect when it was allowed to bind to the collagen surface before blood flow was initiated. Addition of an excess of FITC (fluorescein-5-isothiocyanate)-labeled VWF to platelet-reduced blood under these flow conditions demonstrated that the VWF was mainly incorporated into the platelet aggregates. These results indicated that the supplemented VWF stimulates the platelet adhesion onto the collagen surface by enhancing platelet aggregation in the platelet-reduced condition. This also suggests a possibility that supplementation of VWF to individuals with thrombocytopenia might be effective for increasing their hemostatic potential. ( IntroductionProper formation of a platelet plug at sites of vascular injury requires a spatially and temporally coordinated series of events that allow circulating platelets to adhere onto exposed collagen, become activated, and recruit additional platelets, and form multicellular aggregates, including platelets that are stabilized by fibrin. Von Willebrand factor (VWF), an adhesive plasma glycoprotein, has been indicated to play fundamental roles in the platelet plug formation under physiologic conditions. 1-4 VWF is composed of identical disulfide-linked subunits, each comprising 2050 amino acid residues and up to 22 carbohydrate chains for a total mass of 250 kDa. 5 VWF subunits are crosslinked at the COOH-terminal ends to form a dimer, and the dimer is further converted to a multimeric form with molecular mass from 5 ϫ 10 2 kDa to 2 ϫ 10 4 kDa by intersubunit disulfide linkages at the NH 2 -terminal ends of the dimers. 6 VWF is present in the circulation at a plasma concentration of 5 to 10 g/mL. It is also released from ␣-granules of megakaryocytes and platelets and Weibel-Palade bodies of endothelial cells. 7,8 VWF was shown to have a critical role in platelet adhesion to a collagen surface under flow conditions, especially under high shear rate. 4,9,10 Although platelets do not bind human VWF in solution under low shear rate, VWF binds reversibly with platelet glycoprotein (GP) Ib under high shear rate, and shear stress induces a permanent interaction between VWF and integrin ␣ ⌱⌱b ␤ 3 (GPIIb/IIIa) after the initial binding of GPIb with VWF. 1,11 Moroi et al 12 found that the reversible binding of platelets to immobilized VWF and the tethering speed of platelets was related to the density of VWF on the surface. These and many other r...

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Prospective Study on Soluble Thrombomodulin and von Willebrand Factor and the Risk of Ischemic and Hemorrhagic Stroke

Cited by 18 publications

References 29 publications

Fibrin D-Dimer, Tissue-Type Plasminogen Activator, von Willebrand Factor, and Risk of Incident Stroke in Older Men

Fibrin D-Dimer, Tissue-Type Plasminogen Activator, von Willebrand Factor, and Risk of Incident Stroke in Older Men

Hemostatic Factors as Risk Markers for Intracerebral Hemorrhage

Von Willebrand factor accelerates platelet adhesion and thrombus formation on a collagen surface in platelet-reduced blood under flow conditions

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