Congenital Coagulopathies

Question 1

Who described the vWD as the most prevalent inherited mucocutaneous bleeding disorder?

Answer 1

Finnish professor Erik von Willebrand

Question 2

Both quantitative and functional abnormalities lead to decreased platelet adhesion to injured vessel walls, impairing primary hemostasis.

Answer 2

Quantitative (type 1) or Qualitative (functional, type 2) VWF abnormalities

Question 3

T/F: vWD inheritance is autosomal dominant and affects both sexes

Answer 3

TRUE

Question 4

vWF is a multimeric glycoprotein whose molecular mass ranges from

Answer 4

500,000 - 20,000,000 Daltons

Question 5

Largest molecule in the human plasma

Answer 5

vWF

Question 6

What is the plasma concentration of vWF?

Answer 6

0.5 to 1.0 mg/dL

Question 7

VWF is synthesized in the endoplasmic reticulum of endothelial cells and stored in their cytoplasmic in the _

Answer 7

Weibel-Palade bodies

Question 8

vWF is also synthesized in megakaryocytes and stored in the

Answer 8

alpha granules of platelets

Question 9

T/F: The VWF gene consists of 52 exons spanning 178 kilobase pairs (kb) on chromosome 12

Answer 9

TRUE

Question 10

At the time of storage, a propeptide known as __, becomes cleaved from the end domain D so that mature monomers, already polymerized consists of 2050 AA

Answer 10

vWF antigen II

Question 11

Cleavage function which also appears to modulate acute inflammation, stroke, and myocardial infarction.

Answer 11

ADAMTS13

Question 12

Domain that supports a receptor site
for collagen and a binding site (ligand) for platelet receptor glycoprotein (GP) Ib/IX/V and heparin

Answer 12

Domain A

Question 13

Domain that provides a site that binds platelet receptor GPIIb/IIIa (aIIb3)

Answer 13

Domain C

Question 14

Domain that provides the carrier site for factor VIII

Answer 14

Domain D

Question 15

Quantitative ristocetin cofactor activity, also called VWF activity. VWF activity is measured by the ability of ristocetin to cause agglutination of reagent platelets by the patient’s VWF.

Answer 15

VWF:RCo

Question 16

Collagen binding assay, a second VWF activity assay. Large VWF multimers bind immobilized target collagen, predominantly collagen III.

Answer 16

VWF:CB

Question 17

Automated nephelometric activity assay that employs latex microparticles and monoclonal anti-glycoprotein I–VWF receptor, a third method for assaying VWF activity.

Answer 17

VWF:Immunoactivity

Question 18

Activity assay that employs ristocetin-triggered bind- ing of recombinant glycoprotein Ib (GPIb), detected by LIA or CLIA.

Answer 18

VWF:GPIbR

Question 19

Activity assay that employs recombinant gain-of- function GPIb that binds the VWF A1 domain without the need for ristocetin. Reaction is detected using LIA

Answer 19

VWF:GPIbM

Question 20

Ristocetin-induced platelet aggregometry, uses ristocetin and patient’s own platelets, in contrast to the VWF: RCo, which uses reagent platelets.

Answer 20

RIPA

Question 21

RIPA method is also called the

Answer 21

Ristocetin response curve

Question 22

Its primary function is to mediate platelet adhesion to subendothelial collagen in areas of high flow rate and high shear force, as in capillaries and arterioles

Answer 22

Factor VIII

Question 23

Are best equipped to serve the adhesion function

Answer 23

high-molecular-weight (HMW-VWF) mul- timers

Question 24

Quantitative VWF deficiency caused by one of several autosomal dominant frameshifts, nonsense mutations, or deletions that may occur anywhere in the VWF gene

Answer 24

Type 1 VWD

Question 25

There is mild to moderate systemic bleeding, usually after a hemostatic challenge such as dental extraction or surgery.

Answer 25

Type 1 vWD

Question 26

Encompasses four qualitative VWF abnormalities. VWF levels may be normal or moderately decreased, but VWF function is consistently reduced.

Answer 26

Type 2 vWD

Question 27

Arises from well-characterized autosomal dominant point mutations in the A2 and D1 structural domains of the VWF molecule

Answer 27

Subtype 2A vWD

Question 28

Mutations within the A1 domain raise the affinity of VWF for platelet GPIb/IX/V, its customary binding site; these are hence “gain-of-function” mutation

Answer 28

Subtype 2b vWD

Question 29

Subtype 2B VWD may be confirmed using a specially designed

Answer 29

Reduced-concentration, ristocetin-induced (RIPA) platelet agglutination assay

Question 30

A platelet mutation that raises GPIb affinity for normal HMW-VWF multimers creates a clinically similar disorder called

Answer 30

Platelet-type VWD (PT-VWD) or pseudo-VWD

Question 31

Describes a qualitative VWF variant that possesses poor platelet receptor binding despite generating a normal multimeric distribution pattern in electrophoresis.

Answer 31

Subtype 2M VWD

Question 32

An autosomal VWF gene missense mutation in the D9 domain impairs the protein’s factor VIII binding site function

Answer 32

Subtype 2N von Willebrand disease (Normandy variant; autosomal hemophilia).

Question 33

Subtype 2N is also known as

Answer 33

Autosomal Hemophilia

Question 34

The diagnosis of VWD subtype 2N is confirmed using a __ detects the specific mutation responsible for the abnormal FVIII binding function

Answer 34

Molecular assay

Question 35

“Null allele” VWF genetranslation or deletion mutations that may occur anywhere on the gene produce severe mucocutaneous and anatomic hemorrhage in compound heterozygotes or, in consanguinity, homozygotes

Answer 35

Type 3 vWD

Question 36

Is proportionally diminished or absent, and primary and secondary hemostasis is impaired

Answer 36

Factor VIII

Question 37

The standard VWD test panel must incorporate at what three primary assays

Answer 37

• vWF:Ag
• VWF activity by ristocetin cofactor assay (VWF:RCo) or equivalent,
• Coagulation factor VIII activity.

Question 38

It is the most prominent member of the primary VWD laboratory profile

Answer 38

Quantitative VWF;Ag assay

Question 39

Introduced in 1956 as an unsuccessful antibiotic, is added to in vitro patient plasma where it unfolds the VWF molecule and reduces repelling negative charges, enabling HMW-VWF multimers to bind reagent platelet membrane GPIb/IX/V receptors

Answer 39

Ristocetin

Question 40

Typically performed using a platelet aggregometer, employs preserved reagent platelets and measures platelet agglutination, yielding a quantitative measure of VWF function

Answer 40

VWF:RCo assay

Question 41

Performed on platelet- rich plasma as opposed to a preserved platelet suspension used in the VWF:RCo assay.

Answer 41

Low-dose RIPA test