Introduction
The von Willebrand Factor (VWF), observed by physician Erik von Willebrand, plays an important role in stopping the flow of blood. Hemostasis is the first step in healing a wound and is crucial for blood vessel repair. Located on chromosome 12, VWF interacts with functional domains such as the vascular wall, coagulation factor VIII, and platelet receptors.
Function
Upon a vascular injury, such as a paper cut, the von Willebrand factor binds to receptors on platelets, particularly glycoprotein Ib. VWF will also bind to components of the endothelial matrix, such as collagen. Once it is bound to the receptors, factor VIII, and to matrix components, the factor will then create an adhesive bridge to the location of injury by the use of collagen and platelets. Factor VIII is important in activating the process of coagulation. After factor VIII becomes activated, it is cleaved by thrombin.
Structure
The von Willebrand factor contains four domains from A-D. The A and B domains contain 3 different domains and C has two domains, while D has four. Each domain plays a role in different functions. For example, domains D’ and D3 exhibit binding sites for factor VIII. The structure of VWF was changed from the original thought structure in 1986. The original structure showed to be: D1-D2-D’-D3-A1-A2-A3-D4-B1-B2-B3-C1-C2-CK. However, the new shows the structure is D1-D2-D’-D3-A1-A2-A3-D4-C1-C2-C3-C4-C5-C6-CK. The A1 domain of VWF is the binding site Ib alpha glycoprotein and for collagen. The A2 domain is responsible for binding the cleavage site to ADAMTS-13. ADAMTS-13 is a metalloprotease that cleaves the VWF between the tyrosine and methionine located on positions 842 and 843, respectively. The size of VWF is crucial as the bigger the factor, the abler the factor can anchor platelets.
Disease
As VWF plays a role in coagulation, defects in the VWF leads to an inherited bleeding disorder called von Willebrand Disease that affects 0.01%-1% of the population. The disease is characterized by low levels of VWF or a dysfunctional VWF. There are three different forms that vary between the degree of deficiency and function. Type one, the most common form, is distinguished by lower than normal levels of VWF. Type II is distinguished by normal levels, but improper function. The third and most severe type shows little to none activity of VWF. As the von Willebrand Factor acts as a carrier protein for factor VIII, a deficiency can also cause Hemophilia.
Interactions
The von Willebrand factor is able to bind to multiple other molecules. Some of these interactions are what cause mutations and loss of functions which leads to von Willebrand Disease. A common molecule that inhibits the platelets activation of VWF is the DNA aptamer ARC1172. The aptamer to the A1 domain of the VWF which blocks glycoprotein Ib ability to bind. Another DNA aptamer, ARC1779, is also able to bind and inhibit platelet activation.
