VWF Gene and Protein Function Quiz

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Questions and Answers

What is the length of the VWF cDNA?

~6.5 kb

~176 kb

~ 8.7 kb (correct)

~25 kb

What is the location of the VWF gene on chromosome 12?

12q24.1

12p13.31 (correct)

12p12.1

12q13.2

What is the size of the VWF pseudogene located on chromosome 22?

~6.5 kb

~176 kb

~25 kb (correct)

~ 8.7 kb

Which of the following are types of secretory organelles that store VWF?

Weibel–Palade bodies (C), α-granules (D) Signup and view all the answers

What is the function of the VWF propeptide?

It is not essential for VWF function. (B) Signup and view all the answers

What is the primary function of VWF?

It is involved in the formation of blood clots. (D) Signup and view all the answers

Which of the following is NOT a domain found in the mature VWF subunit?

D1 (B) Signup and view all the answers

What is the approximate homology between the VWF gene and the VWF pseudogene?

97% (A) Signup and view all the answers

What is the primary translation product of the VWF gene?

A pre-proVWF molecule with 2,813 amino acid residues (C) Signup and view all the answers

Which of the following proteins is NOT found in α-granules?

Fibrinogen (C) Signup and view all the answers

What initiates the uncoiling of VWF helices to form ultra-large VWF strings?

Exposure to neutral pH (C) Signup and view all the answers

Which of the following receptors is NOT involved in the clearance of VWF from circulation?

GPIbα (A) Signup and view all the answers

Which domains of VWF are primarily responsible for binding to the subendothelial collagen matrix?

VWF-A1 and VWF-A3 (C) Signup and view all the answers

What is the main function of VWF in relation to coagulation factor VIII (FVIII)?

Prevents FVIII from accelerated clearance and proteolysis (A) Signup and view all the answers

What is the primary characteristic of von Willebrand disease (VWD)?

Excessive mucocutaneous bleeding (D) Signup and view all the answers

Which mutation impact VWF binding to clearance receptors, leading to reduced plasma levels?

Type 2B von Willebrand disease (C), Type 1 von Willebrand disease (D) Signup and view all the answers

Which protein is primarily associated with von Willebrand disease?

Von Willebrand factor (VWF) (A) Signup and view all the answers

Which type of von Willebrand disease is characterized by a complete absence of von Willebrand factor?

Type 3 VWD (A) Signup and view all the answers

What percentage of individuals with von Willebrand disease may be asymptomatic?

Approximately 1% (C) Signup and view all the answers

What is a common bleeding manifestation in women with von Willebrand disease?

Menorrhagia (B) Signup and view all the answers

Which type of VWD is caused by qualitative abnormalities of von Willebrand factor?

Type 2 VWD (C) Signup and view all the answers

Which of these bleeding manifestations is least associated with von Willebrand disease?

Severe arterial blockage (C) Signup and view all the answers

What factor contributes to overdiagnosis and underdiagnosis of VWD?

All of the above (D) Signup and view all the answers

Which of the following is NOT a true statement about VWD type 1?

Type 1 VWD is characterized by a complete absence of VWF. (B) Signup and view all the answers

What is the primary distinction between VWD type 1 and VWD type 2?

Type 2 VWD results in more frequent and heavier bleeding. (A) Signup and view all the answers

What is the most severe type of VWD?

Type 3 VWD (D) Signup and view all the answers

What is the primary characteristic of VWD type 1C?

Increased plasma clearance of VWF. (B) Signup and view all the answers

Which organization played a role in the updated guidelines for VWD diagnosis?

American Society of Hematology (ASH) (A) Signup and view all the answers

What is the primary focus of molecular genetic testing in VWD diagnosis?

Identifying genetic variations in the VWF gene (B) Signup and view all the answers

What does the term 'haemostatic challenges' refer to in the context of VWD?

Situations that can increase the risk of bleeding (A) Signup and view all the answers

Why might bleeding symptoms in less severe forms of VWD not present until later in life?

The absence of significant haemostatic challenges may delay symptom onset. (B) Signup and view all the answers

Which of the following is not a factor influencing the size of Weibel-Palade bodies (WPBs)?

The presence of the signal peptide (C) Signup and view all the answers

What is the primary mechanism by which VWF multimers form in the Golgi apparatus?

Formation of disulfide bonds between the D3 domains (A) Signup and view all the answers

What is the role of ADAMTS13 in the VWF life cycle?

Reduces the size of prothrombotic VWF strings (A) Signup and view all the answers

What is the characteristic shape of Weibel-Palade bodies?

Cigar-shaped (A) Signup and view all the answers

What triggers the stimulated secretion of VWF from endothelial cells?

Presence of thrombin (B) Signup and view all the answers

What is the significance of the propeptide in VWF multimerization?

It promotes the formation of disulfide bonds between the D3 domains (D) Signup and view all the answers

What is the function of VWF in the coagulation cascade?

To bind platelets to the site of injury (B) Signup and view all the answers

Which of the following describes the process of basal secretion of VWF?

Spontaneous release of VWF from single WPBs into the circulation (D) Signup and view all the answers

What is the significance of the unraveling of the tubular VWF structure upon exposure to physiological pH?

It promotes the binding of VWF to platelets (C) Signup and view all the answers

What is the term used to describe the nanoclusters of VWF multimers that are transported through the Golgi apparatus?

Quanta (D) Signup and view all the answers

Study Notes

Von Willebrand Disease (VWD)

VWD is the most common inherited bleeding disorder in humans.
It's characterized by defects in the concentration, structure, or function of von Willebrand factor (VWF).
VWF is a crucial glycoprotein involved in normal hemostasis, specifically in platelet binding to subendothelium and platelet-platelet interactions.
VWF also carries the procoagulant factor VIII.
VWD shows worldwide distribution and is also common in other animal species like dogs.
Prevalence in humans varies based on diagnostic approach.
VWD is estimated to affect 125 per million people with bleeding symptoms, and approximately 1% are asymptomatic.
VWD is categorized into three primary types: type 1, type 2, and type 3.

Type 1 VWD

Characterized by a partial quantitative deficiency of VWF.
This is the most common type.
VWF levels range from 30 to 50 IU/dL.
Symptoms range from mild to moderate bleeding.
Causes include decreased VWF synthesis, impaired storage and secretion, and or accelerated VWF clearance.
Symptoms include mucocutaneous bleeding, nosebleeds, bruising, bleeding from wounds, menorrhagia (in females) or postpartum bleeding (in females), and bleeding after surgery.

Type 2 VWD

Represents dysfunctional forms of VWF molecules.
Symptoms are caused by changes in VWF function and structure.
Divided into subtypes 2A, 2B, 2M, and 2N.
Type 2A: decreased VWF-platelet interaction due to loss of large and intermediate VWF multimers.
Type 2B: increased affinity of VWF for platelet GPIb, leading to reduced HMWMs.
Type 2M: reduced VWF affinity for collagen and platelets
Type 2N: reduced VWF affinity for factor VIII.

Type 3 VWD

Characterized by a near-complete absence of VWF in both plasma and platelets.
The most severe type.
VWF antigen levels are typically very low (<3 IU/dL).
This results in a significant reduction in factor VIII.
Characterized by high frequency of homozygous gene defects or compound heterozygous.
VWF is affected on both alleles.
Possible complications from replacement therapy include the development of allo-antibodies.

VWF Gene

The gene encoding VWF (VWF) maps to the short arm of chromosome 12 (12p13.31).
Contains 52 exons.
Also contains a partial unprocessed VWF pseudogene, located on chromosome 22.

VWF Life Cycle

Synthesized in endothelial cells and megakaryocytes, stored in Weibel-Palade bodies (WPBs) and alpha granules, respectively.
In transit through the Golgi, propeptide is cleaved from the mature protein
VWF multimers coalesce into nanoclusters.
Upon stimulation (agonists), VWF multimers are released into circulation.
VWF strings are proteolyzed by ADAMTS13, and released into the plasma

VWF Functions

Involved in platelet recruitment to sites of vascular injury.
VWF multimers act as a carrier protein for factor VIII (prevent clearance & proteolysis)

Diagnosis of VWD

Requires attention to personal and family history of bleeding and lab evaluation consistent with a quantitative/qualitative VWF defect.
Lab tests include VWF antigen, VWF activity, VWF-RCo, FVIII:C, Collagen Binding Assay (VWF:CB).

Lab Evaluation for VWD

Platelet count may be normal.
Clotting time may be prolonged, potentially normal in mild cases depending on platelet VWF content.
Partial thromboplastin time (PTT) may vary depending on plasma FVIII levels.

VWD Subtype Characterization

Ristocetin-induced platelet aggregation assay (RIPA) can differentiate between different VWD types.
VWF multimer analysis aids in characterization.
Specialized tests involving FVIII binding assay is to distinguish type 2N from mild hemophilia A.

VWD Management

Treatment options are type-specific with mild/moderate VWD responding to desmopressin for temporary increase in circulation VWF and Factor VIII (FVIII).
Severe VWD requires transfusions with enriched-VWF/FVIII concentrates.
Prophylactic treatments.

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Description

Test your knowledge on the von Willebrand factor (VWF) gene and its related functions. This quiz covers topics such as the gene's location, size, and the roles of secretory organelles in storing VWF. Evaluate your understanding of the VWF propeptide and domains present in the mature VWF subunit.