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Genetic determinants of Von Willebrand factor and the risk of cardiovascular disease

Author: Janine Loon
Publisher: Erasmus University Rotterdam 2012-11-09
Edition/Format: Book Book : English
Summary:
textabstractNormal haemostasis requires a delicate balance between procoagulant and anticoagulantfactors. Disruption of this balance may lead to bleeding disorders, such as hemophilia,or thrombotic disorders, including deep vein thrombosis of the leg. As Virchowalready reported in 1877, properties of the blood vessel wall, the blood flow and bloodconstituents contribute to the formation of thrombi in either veins or  Read more...
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Document Type: Book
All Authors / Contributors: Janine Loon
ISBN: 978-94-6169-293-1
Language Note: English
Unique Identifier: 6892890974
Awards:

Abstract:

textabstractNormal haemostasis requires a delicate balance between procoagulant and anticoagulantfactors. Disruption of this balance may lead to bleeding disorders, such as hemophilia,or thrombotic disorders, including deep vein thrombosis of the leg. As Virchowalready reported in 1877, properties of the blood vessel wall, the blood flow and bloodconstituents contribute to the formation of thrombi in either veins or arteries. However,through contemporary research the complexity of this process leading to thrombusformation has become more apparent.An important player in thrombus formation is von Willebrand Factor (VWF), a largemultifunctional glycoprotein. VWF initiates adherence of platelets to the injured vesselwall and subsequent platelet aggregation leading inevitably to the formation ofthrombi. In addition, VWF is a carrier protein of coagulation factor VIII (FVIII), therebyprotecting it from clearance.In healthy subjects normal plasma VWF levels range from 0.60 – 1.40 IU/mL and arecharacterized by a large variation. This can be partly attributed to a number of lifestyleand environmental factors, but most importantly to genetic factors.The necessity of maintaining normal VWF levels in the circulation is illustrated bytwo clinical manifestations that may occur when VWF exceeds its normal range. Lowlevels of VWF may lead to bleeding, which is known as von Willebrand Disease (VWD),the most common inherited bleeding disorder in humans. To the contrary, high VWFantigen (VWF:Ag) levels are associated with an increased risk of venous thrombosisand arterial thrombosis, including myocardial infarction (MI) and ischemic stroke.

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