VWF Gene and Protein Function Quiz

A congenital bleeding disorder caused by defects in von Willebrand factor (VWF), a key protein involved in blood clotting.

VWF is a large plasma glycoprotein that plays a crucial role in blood clotting. It helps platelets stick to damaged blood vessels and also carries factor VIII, another vital clotting factor.

The most common symptom is excessive bleeding, especially from the nose (nosebleeds), skin (bruising) and mucous membranes. It can also lead to heavier than normal menstrual bleeding and bleeding after surgery or injury.

It is the most common inherited bleeding disorder, affecting people worldwide.

VWD is classified into types based on the nature of the defect in VWF. Type 1 involves a reduced amount of VWF, Type 3 lacks VWF completely, and Type 2 has abnormalities in VWF structure and function.

The specific type of VWD influences the severity of bleeding symptoms.

VWD is diagnosed through blood tests that evaluate the levels and function of VWF. Treatment options include replacement therapy with VWF concentrates or medications that stimulate VWF production.

VWF exists in a globular shape in the blood, carrying Factor VIII, a protein crucial for clotting.

When VWF is exposed to a neutral pH, it transforms into an extended, stringy form.

VWF binds to collagen in damaged blood vessels, changing into an active form that helps platelets stick together.

The enzyme ADAMTS13 helps break down VWF, releasing different sizes of VWF into the blood.

Type 1 VWD, characterized by a partial quantitative deficiency of VWF, is the most common type, accounting for the majority of VWD cases. It typically results in mild to moderate bleeding symptoms.

Type 2 VWD involves qualitative defects in VWF, leading to abnormal function of the protein. It's further classified into subtypes (2A, 2B, 2M, 2N) based on the specific functional and structural defects. Type 2 VWD typically causes more frequent and severe bleeding episodes than type 1.

Type 3 VWD is the rarest and most severe form, characterized by a near-complete absence of VWF. It often presents with severe bleeding episodes even with minor injuries.

Type 1C VWD is a recently recognized subtype of VWD. It's characterized by a faster breakdown of VWF in the blood, leading to a lower VWF level despite the body producing enough VWF.

Platelet-type VWD (also called pseudo-VWD) involves a problem with the interaction between platelets and VWF. This can lead to reduced or abnormal platelet function, contributing to bleeding issues.

VWD can be difficult to diagnose, especially as symptoms can vary widely in severity and appear late in life for some. Misdiagnosis, overdiagnosis, and underdiagnosis can occur.

Diagnosing VWD requires specialized testing, including phenotypic assays and genetic testing of the VWF gene to assess the quantity and function of VWF.

The 2021 ASH/ISTH/NHF/WFH guidelines have shifted the definition of Type 1 VWD, now including patients previously considered to be at risk for bleeding but with VWF levels between 30 and 50 IU/dl.

Von Willebrand factor (VWF) multimers coalesce into nanoclusters called quanta, with a median size of 500 nm.

The size of Weibel-Palade bodies (WPBs) is directly related to their ability to help with blood clotting.

The number of VWF quanta and their movement through the ER, Golgi, and TGN determine the WPB size.

During stimulated secretion, multiple WPBs clump together into a 'secretory pod' before releasing their contents into the bloodstream.

VWF dimers are created through disulfide bonding in the CK domains as VWF enters the endoplasmic reticulum (ER).

In the Golgi apparatus, the propeptide is separated from the mature subunit by furin enzyme activity.

The acidic environment of the Golgi facilitates non-covalent binding of the propeptide, promoting the formation of disulfide bonds between D3 domains for multimerization.

VWF multimers arrange in a right-handed helix, ultimately forming the cigar-shaped Weibel-Palade bodies (WPBs).

WPBs can spontaneously fuse with the cell membrane and release their contents into the circulation, known as basal secretion.

Exposure to physiological pH causes the tubular VWF structure to uncoil into long strings composed of multiple VWF multimers, which are in their active, platelet-binding conformation.

A gene located on chromosome 12 that encodes von Willebrand factor (VWF). It spans approximately 176 kilobases and contains 52 exons.

A non-functional copy of the VWF gene located on chromosome 22. It has a high degree of similarity to the VWF gene but cannot produce functional transcripts.

The initial product formed after the VWF gene is transcribed and translated. It contains a signal peptide, a propeptide, and the mature VWF subunit.

The protein encoded by the VWF gene. It plays a crucial role in blood clotting by binding to platelets and aiding in the formation of a blood clot at the site of injury.

Elongated storage organelles found in endothelial cells. They store VWF and other proteins involved in inflammation, angiogenesis, and tissue repair.

The most abundant secretory granules in platelets. They contain VWF, platelet factor 4, thrombospondin, and fibrinogen.

Endothelial cells are the cells that line the inside of blood vessels.

Megakaryocytes are large cells in the bone marrow that produce platelets.

The process by which VWF is synthesized, stored, released, and degraded.

The process by which a blood clot forms to stop bleeding.