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CLIN CHEM 1 (LABORATORY) > CONGENITAL COAGULOPATHIES - HEMA 2 MTAP 2 > Flashcards

CONGENITAL COAGULOPATHIES - HEMA 2 MTAP 2 Flashcards

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1
Q

VWD was first described by who?

A

Finnish professor Erik von Willebrand

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2
Q

When was the VWD first described?

A

1926

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3
Q

the most prevalent inherited mucocutaneous bleeding disorder

A

Von Willebrand Disease

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4
Q

Any one of dozens of germline mutations may cause VWD as these mutations produce what?

A

quantitative (type 1) or qualitative (functional, type 2)

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5
Q

Type 1 VWD is qualitative or quantitative?

A

Quantitative

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6
Q

Type 2 VWD is qualitative or quantitative?

A

Qualitative

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7
Q

What are the types of VWF abnormalities?

A

quantitative (type 1) or qualitative (functional, type 2)

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8
Q

Both quantitative and functional abnormalities lead to what?

A

decreased platelet adhesion

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9
Q

decreased platelet adhesion to injured vessel walls impairs what?

A

impairs primary hemostasis

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10
Q

When solely defined by laboratory assays as VWF deficiency, VWD is reputed to afflict approximately how many percent of the global population?

A

1%

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11
Q

when defined by the number of patients who experience bleeds serious enough to seek medical assistance, prevalence is how many?

A

1 in 20,000

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12
Q

when defined by the number of patients who experience bleeds serious enough to seek medical assistance, prevalence is how many in percent?

A

0.05%

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13
Q

The prevalence of VWD in women who report menorrhagia is how many percent of women?

A

24%

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14
Q

What genetic trait or condition is VWD?

A

autosomal dominant

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15
Q

VWD affects what sex?

A

affects both sexes

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16
Q

This is a multimeric glycoprotein

A

VWF

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17
Q

VWF is what type of glycoprotein?

A

multimeric glycoprotein

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18
Q

Molecular mass of VWF?

A

500,000 to 20,000,000 Daltons

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19
Q

This is the largest molecule in human plasma

A

VWF

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20
Q

plasma concentration of VWF

A

0.5 to 1.0 mg/dL

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21
Q

a great deal more of VWF is readily available on demand from where?

A

storage organelles

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22
Q

VWF is synthesized TWO locations

A

endoplasmic reticulum of
endothelial cells & megakaryocytes

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23
Q

VWF is synthesized in the endoplasmic reticulum of endothelial cells and stored where?

A

in their cytoplasmic Weibel-Palade bodies

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24
Q

VWF is synthesized in megakaryocytes and stored where?

A

the a-granules of platelets

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25
Q

Weibel-Palade bodies and a-granules release what?

A

VWF

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26
Q

Weibel-Palade bodies and a-granules release VWF in response to a variety of what?

A

hemostatic and inflammatory stimuli

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27
Q

The VWF gene consists of how many exons?

A

52 exons

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28
Q

The VWF gene consists of 52 exons spanning a kilobase of how much?

A

178 kilobase pairs

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29
Q

Where is the VWF gene located?

A

located on the p arm of chromosome 12

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30
Q

The translated protein is a monomer of how many amino acids?

A

2813 amino acids

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31
Q

The translated protein is a monomer of 2813 amino acids composed of how many domains?

A

four structural domains, A through D

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32
Q

It is a monomer of 2813 amino acids composed of four structural domains, A through D.

A

translated protein

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33
Q

The monomers of the translated proteins become glycosylated, then form what?

A

dimers and oligomers

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34
Q

The monomers become glycosylated, then form dimers and oligomers that migrate to the aforementioned storage organelles, where they polymerize to form what?

A

Ultralarge VWF (UL-VWF) multimers

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35
Q

At the time of storage, a propeptide, known as ????? becomes cleaved from the end of domain D

A

VWF antigen II

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36
Q

VWF antigen II becomes cleaved from the end of what domain?

A

domain D

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37
Q

when mature monomers are polymerized, how many amino acids does it consist?

A

2050 amino acids

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38
Q

This may occur anywhere on the VWF gene

A

VWD mutations

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39
Q

Where do VWD mutations occur?

A

may occur anywhere on the VWF gene

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40
Q

They bind platelets

A

VWF multimers bind platelets

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41
Q

It cleaves the now linear UL-VWF multimers, yielding multimers of various masses

A

ADAMTS13

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42
Q

This results in the retention of circulating UL-VWF multimers

A

ADAMTS13 deficiency

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43
Q

ADAMTS13 deficiency is the basis for what devastating disorder?

A

thrombotic thrombocytopenic purpura

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44
Q

It is the basis for the devastating disorder thrombotic thrombocytopenic purpura

A

ADAMTS13

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45
Q

What does the ADAMTS13 cleavage function appear to modulate?

A

(1) acute inflammation (2) stroke (3) myocardial infarction

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46
Q

This part of the VWF monomer supports its various functions

A

Epitopes of the structural domains

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47
Q

This domain supports a receptor site for collagen

A

Domain A

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48
Q

What is domain A?

A

(1) supports a receptor site for collagen (2) binding site (ligand) for PLT receptor GP Ib/IX/V (3) Heparin

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49
Q

This domain is a binding site (ligand) for platelet receptor glycoprotein (GP) Ib/IX/V

A

Domain A

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50
Q

This domain is a binding site (ligand) for heparin

A

Domain A

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51
Q

This domain provides a site that binds platelet receptor GPIIb/IIIa

A

Domain C

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52
Q

Domain C provides a site that binds what PLT receptor?

A

GPIIb/IIIa

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53
Q

Domain A provides a binding site for what PLT receptor?

A

GP Ib/IX/V

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54
Q

This domain provides the carrier site for factor VIII

A

Domain D

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55
Q

Domain D provides the carrier site for what factor?

A

FVIII

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56
Q

On release from intracellular stores, a percentage of VWF multimers complex with what?

A

factor VIII

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57
Q

This protects factor VIII from proteolysis

A

VWF

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58
Q

VWF protects what factor?

A

FVIII

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59
Q

VWF protects FVIII from what?

A

proteolysis

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60
Q

This prolongs plasma half-life of FVIII

A

VWF

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61
Q

VWF prolonging FVIII plasma half-life from a few minutes to how long?

A

8-12 hrs

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62
Q

FVIII has a half-life of a few minutes under what condition?

A

when free

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63
Q

FVIII has a half-life of 8-12 hrs under what condition?

A

When bound to VWF

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64
Q

This is the carrier molecule of FVIII

A

VWF

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65
Q

What is the primary function of VWF?

A

to mediate platelet adhesion to subendothelial colagen in areas of high flow rate and high shear force (capillaries, arterioles)

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66
Q

After being released from the Weibel-Palade bodies, this first unfolds and binds fibrillar intimal collagen exposed during the desquamation of endothelial cells or in a blood vessel injury

A

VWF

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67
Q

VWF first unfolds and binds fibrillar intimal collagen exposed during what?

A

during the desquamation of endothelial cells or in a blood vessel injury

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68
Q

platelets adhere through their GPIb/IX/V site to the what?

A

VWF “carpet.”

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69
Q

These are best equipped to serve the adhesion function

A

high-molecular-weight (HMW-VWF) multimers

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70
Q

What is the function of HMW-VWF multimers?

A

adhesion function

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71
Q

When VWF binds GPIb/IX/V, platelets become activated and express a second VWF binding site known as the

A

GPIIb/IIIa

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72
Q

This receptor binds arginine-glycine-aspartic acid (arginyl-glycylaspartic acid, RGD)

A

GPIIb/IIIa

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73
Q

GPIIb/IIIa receptos binds what sequence?

A

arginine-glycine-aspartic acid (arginyl-glycylaspartic acid, RGD)

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74
Q

arginine-glycine-aspartic acid (arginyl-glycylaspartic acid, RGD) are richly distributed to where?

A

VWF and fibrinogen molecules

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75
Q

This mediates irreversible platelet-to-platelet aggregation

A

arginine-glycine-aspartic acid (arginyl-glycylaspartic acid, RGD)

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76
Q

Is platelet aggregation an irreversible or reversible process?

A

Irreversible

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77
Q

These processes are essential to normal primary and secondary hemostasis.

A

adhesion and aggregation

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78
Q

What type of VWF abnormality is qualitative type 1?

A

Structural

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79
Q

What type of VWF abnormality is quantitative type 2?

A

Functional

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80
Q

These reduce platelet adhesion

A

VWF abnormalities

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81
Q

This leads to mucocutaneous hemorrhage of varying severity

A

Structural (qualitative) or quantitative VWF abnormalities

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82
Q

Structural (qualitative) or quantitative VWF abnormalities lead to what kind of hemorrhage?

A

mucocutaneous hemorrhage

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83
Q

Six kinds of mucocutaneous hemorrhages?

A

(1) Epistaxis (2) Ecchymosis (3) menorrhagia (4) hematemesis (5) gastrointestinal bleeding (6) surgical bleeding

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84
Q

severe quantitative VWF deficiency creates what?

A

FVIII deficiency

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85
Q

This is created as a result of the inability to protect unbound factor VIII from proteolysis

A

FVIII deficiency

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86
Q

FVIII deficiency is a result of what?

A

a result of the inability to protect unbound factor VIII from proteolysis

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87
Q

FVIII deficiency is created as a result of the inability to protect unbound factor VIII from what?

A

proteolysis

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88
Q

Many “low VWF” people have VWF levels in the intermediate range of what?

A

30% to 50% of normal

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89
Q

People termed as this maintain a factor VIII level sufficient for competent coagulation

A

“Low VWF”

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90
Q

People termed as this have VWF levels in the intermediate range of 30% to 50% of normal

A

“Low VWF”

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91
Q

What are the TWO criteria for a person to have “Low VWF”?

A

(1) VWF levels in the intermediate range of 30% to 50% of normal (2) maintain a factor VIII level sufficient for competent coagution

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92
Q

anatomic bleeding into joints and body cavities accompanies the typical mucocutaneous bleeding pattern of VWD when FVIII levels decrease to what value?

A

less than 30 units/dL

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93
Q

What happens when factor VIII levels decrease to less than 30 units/dL?

A

anatomic bleeding into joints and body cavities accompanies the typical mucocutaneous bleeding pattern of VWD

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94
Q

This is the Customary designation for the combination of factor VIII and VWF

A

FVIII/VWF

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95
Q

Factor VIII binds activated factor IX to form the complex of

A

VIIIa-IXa

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96
Q

This complex digests and activates factor X.

A

VIIIa-IXa

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97
Q

Factor VIII deficiency is called

A

hemophilia A

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98
Q

This binds activated factor IX to form the complex of VIIIa-IXa

A

FVIII

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99
Q

Epitope that is the antigenic target for the VWF immunoassay

A

VWF:Ag

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100
Q

This is measured in a clot-based factor assay

A

Factor VIII coagulant activity (FVIII:C)

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101
Q

This is also called VWF activity

A

Quantitative ristocetin cofactor activity (VWF:RCo)

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102
Q

Quantitative ristocetin cofactor activity (VWF:RCo) is also called

A

VWF activity

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103
Q

This is a second VWF activity assay

A

Collagen binding assay (VWF:CB)

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104
Q

Large VWF multimers bind immobilized target collagen, predominantly what?

A

collagen III

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105
Q

Automated nephelometric activity assay that employs latex microparticles and monoclonal anti-glycoprotein I–VWF receptor

A

VWF:Immunoactivity

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106
Q

This is a third method for assaying VWF activity

A

VWF:Immunoactivity

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107
Q

Activity assay that employs ristocetin-triggered bindng of recombinant glycoprotein Ib (GPIb)

A

VWF:GPIbR

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108
Q

This reaction is detected by LIA or CLIA

A

VWF:GPIbR

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109
Q

Activity assay that employs recombinant gain-of-function GPIb that binds the VWF A1 domain without the need for ristocetin

A

VWF:GPIbM

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110
Q

This Reaction is detected using LIA

A

VWF:GPIbM

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111
Q

VWF:GPIbM is detected using what?

A

LIA (latex immunoassay)

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112
Q

VWF:GPIbR is detected using what?

A

LIA or CLIA (Chemiluminescence immunoassay)

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113
Q

This is a quantitative VWF deficiency

A

Type 1 VWD

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114
Q

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

A

Type 1 VWD

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115
Q

Type 1 comprises of what percent of VWD cases?

A

40-70%

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116
Q

True or False: The plasma concentrations of all VWF multimers and factor VIII are variably, albeit proportionally, reduced.

A

TRUE

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117
Q

In this VWD, there is mild to moderate systemic bleeding, usually after a hemostatic challenge such as dental extraction or surgery

A

Type 1 VWD

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118
Q

This is a common complaint that leads to the diagnosis of VWD

A

menorrhagia, which predicts postpartum hemorrhage

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119
Q

This encompasses four qualitative VWF abnormalities

A

Type 2 VWD

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120
Q

In this type of VWD, VWF levels may be normal or moderately decreased, but VWF function is consistently reduced.

A

Type 2 VWD

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121
Q

In type 2 VWD, what are its characteristics?

A

VWF = normal or moderately decreased; VWF function = consistently reduced

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122
Q

Approximately how many percent of all VWD patients suffer from subtype 2A?

A

10 - 20%

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123
Q

This type of VWD comprises 40-70% of VWD cases

A

Type 1 VWD

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124
Q

This type of VWD comprises 10-20% of VWD cases

A

Subtype 2A VWD

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125
Q

This type of VWD arises from well-characterized autosomal dominant point mutations in the A2 and D1 structural domains of the VWF molecule

A

Subtype 2A VWD

126
Q

Subtype 2A VWD arises from well-characterized autosomal dominant point mutations in what structural domains of the VWF molecule?

A

A2 and D1 structural domains of the VWF molecule

127
Q

These mutations render VWF susceptible to increased proteolysis by ADAMTS13

A

Subtype 2A VWD

128
Q

subtype 2A VWD is caused by mutations that render VWF susceptible to what?

A

increased proteolysis

129
Q

What leads to a predominance of small molecular-weight plasma multimers

A

increased proteolysis by ADAMTS13

130
Q

True or False: The smaller multimers support more platelet adhesion activity than the normal high- or intermediate-molecular weight multimers.

A

False: The smaller multimers support less platelet adhesion activity than the normal high- or intermediate-molecular weight multimers.

131
Q

These support less platelet adhesion activity than the normal high- or intermediate-molecular weight multimers.

A

Smaller multimers

132
Q

Patients with this type of VWD have normal or slightly reduced VWF antigen levels as measured by immunoassay

A

subtype 2A VWD

133
Q

This is a result of the loss of the high-molecular-weight and intermediate-molecular-weight multimers essential for platelet adhesion

A

VWF antigen levels: normal or slightly reduced, VWF activity: moderate to markedly reduced

134
Q

What are the characteristics of patients with Subtype 2A VWD?

A

VWF antigen levels: normal or slightly reduced, VWF activity: moderate to markedly reduced

135
Q

Patients with this type of VWD are identified in LESS THAN 5% of all VWD patients

A

Subtype 2B VWD

136
Q

Patients with subtype 2B VWD are identified in what percent of VWD cases?

A

LESS THAN 5%

137
Q

Patients with subtype 2B VWD have mutations in what domain of the VWF?

A

A1 domain

138
Q

In this type of VWD, this VWD raise the affinity of VWF for platelet GPIb/IX/V, its customary binding site

A

subtype 2B VWD

139
Q

Patients with subtype 2B VWD raise the affinity of VWF for what platelet glycoprotein?

A

GPIb/IX/V

140
Q

GPIb/IX/V is the customary binding site of what VWD?

A

subtype 2B VWD

141
Q

This VWD are these are hence “gain-of-function” mutations

A

subtype 2B VWD

142
Q

What type of mutation is the subtype 2B VWD?

A

“gain-of-function” mutations

143
Q

These multimers spontaneously bind resting platelets

A

HMW-VWF multimers

144
Q

HMW-VWF multimers spontaneously bind what?

A

resting platelets

145
Q

Why are abnormal HMW-VWF multimers consequently unavailable for normal platelet adhesion?

A

as they are cleared with the bound platelets

146
Q

This is characterized by lack of HMW-VWF multimers, but intermediate-molecular-weight multimers may still be present

A

electrophoretic multimer pattern

147
Q

The electrophoretic multimer pattern is characterized by what?

A

lack of HMW-VWF multimers, but intermediate-molecular-weight multimers may still be present

148
Q

Subtype 2B VWD may be confirmed using a specially designed reduced-concentration called

A

ristocetin-induced (RIPA) platelet agglutination assay

149
Q

Patients with Subtype 2B VWD may also express this disease

A

moderate thrombocytopenia

150
Q

This is caused by chronic platelet activation because multimer-coated platelets indiscriminately bind the endothelium and become cleared

A

moderate thrombocytopenia

151
Q

moderate thrombocytopenia caused by what?

A

chronic platelet activation

152
Q

Why is moderate thrombocytopenia caused by chronic platelet activation?

A

because multimer-coated platelets indiscriminately bind the endothelium and become cleared

153
Q

This platelet mutation creates a clinically similar disorder called platelet-type VWD (PT-VWD) or pseudo-VWD

A

platelet mutation that raises GPIb affinity for normal HMW-VWF multimers

154
Q

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

A

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

155
Q

platelet-type VWD (PT-VWD) is also called

A

pseudo-VWD

156
Q

platelet-type VWD (PT-VWD) or pseudo-VWD is caused by what?

A

A platelet mutation that raises GPIb affinity for normal HMW-VWF multimers

157
Q

In platelet-type VWD (PT-VWD) or pseudo-VWD, these are lost from the plasma

A

large multimers

158
Q

In this type of VWD, the large multimers also are lost from the plasma, and platelets become adhesive

A

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

159
Q

this is not a true form of VWD

A

Pseudo-VWD

160
Q

PT-VWD’s prevalence is approximately what percent of subtype 2B VWD sufferers?

A

10%

161
Q

This is often mistaken for immune thrombocytopenia

A

platelet-type VWD

162
Q

This describes a qualitative VWF variant that possesses poor platelet receptor binding

A

Subtype 2M VWD

163
Q

What are the characteristics of patients with Subtype 2M VWD?

A

(1) Poor PLT receptor binding (2) Normal multimeric distribution pattern in electrophoresis

164
Q

What is the the distinguishing feature of subtype 2M that separates it from type 1?

A

(1) a discrepancy between the concentration of VWF:Ag (2) its activity as measured using the VWF ristocetin cofactor assay

165
Q

type 1 or subtype 2A is often incorrectly identified as

A

Subtype 2M VWD

166
Q

Subtype 2N VWD is also called

A

Normandy variant

167
Q

This is the autosomal hemophilia

A

Subtype 2N VWD

168
Q

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

A

Subtype 2N VWD

169
Q

Subtype 2N VWD is an autosomal VWF gene missense mutation in what domain?

A

Domain 9

170
Q

What type of mutation is the Subtype 2N VWD?

A

VWF gene missense mutation

171
Q

What is impaired in Subtype 2N VWD?

A

impairs the protein’s factor VIII binding site function

172
Q

Subtype 2N VWD is present in what percent of VWD patients?

A

Less than 5%

173
Q

This results in factor VIII deficiency despite a normal VWF antigen concentration assay result, normal VWF activity, and a normal multimeric pattern

A

Normandy variant

174
Q

What are the characteristics of the Subtype 2N VWD?

A

(1) FVIII deficiency (2) normal VWF antigen conc assay (3) Normal VWF activity (4) Normal multimeric pattern

175
Q

The disorder is also known as autosomal hemophilia

A

Normandy variant

176
Q

Subtype 2N VWD is also known as

A

autosomal hemophilia

177
Q

Why is subtype 2N VWD also known as autosomal hemophilia?

A

because its clinical symptoms are indistinguishable from the symptoms of hemophilia except that it affects both men and women

178
Q

Subtype 2N is suspected when a girl or woman is diagnosed with hemophilia subsequent to what?

A

subsequent to anatomic bleeding symptoms

179
Q

In boys or men, subtype 2N is suspected when a male patient misdiagnosed as a hemophilia A sufferer fails to respond to what?

A

fails to respond to factor VIII concentrate therapy

180
Q

This occurs because free factor VIII has a plasma half-life of mere minutes

A

poor therapeutic response

181
Q

Why does poor therapeutic response in Subtype 2N VWD occurs?

A

because free factor VIII has a plasma half-life of mere minutes.

182
Q

The diagnosis of VWD subtype 2N is confirmed using what?

A

using a molecular assay that detects the specific mutation responsible for the abnormal FVIII binding function.

183
Q

What type of genetic mutation occurs in Type 3 VWD?

A

“Null allele” VWF gene translation or deletion mutations

184
Q

This VWF abnormality has “Null allele” VWF gene translation or deletion mutations

A

Type 3 VWD

185
Q

This may occur anywhere on the gene produce severe mucocutaneous and anatomic hemorrhage in compound heterozygotes or, in consanguinity, homozygotes

A

Type 3 VWD

186
Q

The “Null allele” VWF gene translation or deletion mutationsthat may occur anywhere on the gene produce what?

A

severe mucocutaneous and anatomic hemorrhage

187
Q

In type 3 VWD, severe mucocutaneous and anatomic hemorrhage happen in what?

A

compound heterozygotes or, in consanguinity, homozygotes.

188
Q

This is the most rare form of VWD

A

Type 3 VWD

189
Q

In type 3 VWD, VWF concentration is measured by WHAT?

A

measured by immunoassay or by activity assay is less than 10%

190
Q

In type 3 VWD, VWF concentration is measured by measured by immunoassay or by activity assay is less than what percent?

A

less than 10%

191
Q

In this type of VWD, FVIII is proportionally diminished or absent

A

Type 3 VWD

192
Q

In type 3 VWD, this is proportionally diminished or absent

A

FVIII

193
Q

Definitive diagnosis of VWD depends on the combination what?

A

(1) personal history (2) family history of mucocutaneous bleeding (3) laboratory demonstration of decreased VWF concentration or activity (function)

194
Q

What are the fundamental tests that a physician orders for the laboratory detection and classification of VWD?

A

(1) CBC (2) PT (3) PTT

195
Q

This laboratory test is ordered by the physician to rule out thrombocytopenia as the cause of mucocutaneous bleeding?

A

CBC

196
Q

These tests are ordered to assess the coagulation cascade to rule out a coagulation factor deficiency other than VWF

A

PT and PTT

197
Q

according to the 2009 National Heart Lung and Blood Institute (NHLBI) VWD guidelines, these tests are obsolete/no longer recommended

A

bleeding time test and the PFA-100 or other automated functional platelet assays

198
Q

What are the 3 primary assays to be incorporated in a standard VWD test panel?

A

(1) VWF:Ag (2) VWF activity by ristocetin cofactor assay (VWF:RCo) (3) coagulation factor VIII activity

199
Q

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

A

quantitative VWF:Ag assay

200
Q

This is the traditional reference method for detection and classification of VWD

A

enzyme immunoassay (EIA) methodology

201
Q

For the detection and classification of VWD, this method possesses the best sensitivity to VWF concentrations less than 10% and the best precision.

A

chemiluminescence immunoassay (CLIA)

202
Q

The CLIA method possesses the best sensitivity to VWF concentrations less than what percent?

A

less than 10%

203
Q

This method possesses the best precision for detection of VWD

A

CLIA method

204
Q

This primary assay’s results generally parallel VWF:Ag and VWF:RCo results in VWD types 1 and 3, and may parallel VWF:Ag in subtypes 2A, 2B, and 2M, but are markedly reduced in VWD subtype 2N.

A

Factor VIII assay

205
Q

Factor VIII assay results generally parallel VWF:Ag and VWF:RCo results in what VWD types?

A

VWD types 1 and 3

206
Q

Factor VIII assay results may be parallel in VWF:Ag in what VWD types?

A

subtypes 2A, 2B, and 2M

207
Q

Factor VIII assay results are markedly reduced in what VWD type?

A

VWD subtype 2N

208
Q

Factor VIII assay results may be parallel in what other primary assays?

A

Parallel in (1) VWF:Ag results (2) VWF:RCo results

209
Q

in VWD types 1 and 3, FVIII assay results are parallel with what assay?

A

VWF:Ag and VWF:RCo

210
Q

True or False: FVIII assay results are parallel with VWF:Ag and VWF:RCo results in VWD types 1, 2A, 2B, 2M, and 3

A

TRUE

211
Q

The traditional VWF:RCo assay employs what?

A

ristocetin

212
Q

This traditional assay employs ristocetin

A

VWF:RCo assay

213
Q

When was ristocetin introduced as an unsuccessful antibiotic?

A

1956

214
Q

This 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 re

A

Ristocetin

215
Q

The VWF:RCo assay is typically performed using a what?

A

platelet aggregometer

216
Q

This primary assay employs preserved reagent platelets and measures platelet agglutination, yielding a quantitative measure of VWF function

A

VWF:RCo assay

217
Q

This has been successfully automated but has been partially replaced by automated ristocetin-triggered nonplatelet recombinant GPIbbased LIA and CLIA methods

A

VWF:RCo assay

218
Q

VWF:RCo has been partially replaced by what?

A

automated ristocetin-triggered nonplatelet recombinant GPIb-based LIA and CLIA methods

219
Q

A promising alternative to VWF:RCo and VWF:GPIbR is an assay that incorporates what?

A

incorporates a gain-of-function high-affinity recombinant GPIb protein that resembles the GPIb of PT-VWD platelets.

220
Q

This binds the A1 domain of native VWF without the need for ristocetin

A

GPIb

221
Q

The GPIb binds what domain of the native VWF?

A

A1 domain

222
Q

This assay has been commercialized as a LIA (Innovance VWF Ac, Siemens), and it appears to improve on ristocetin-based assays as it offers smaller VWF detection limits and less variability

A

VWF:GPIbM

223
Q

All VWF activity assays rely on this

A

GPIb binding avidity

224
Q

This is a surrogate for VWF activity

A

GPIb binding avidity

225
Q

the laboratory professional infers qualitative or type 2 VWD, when the ratio of the VWF:RCo, VWF:GPIbR, or
VWF:GPIbM assay value to the VWF:Ag concentration is less than what values?

A

less than 0.5, 0.6, or 0.7

226
Q

when the ratio of the VWF:RCo, VWF:GPIbR, or VWF:GPIbM assay value to the VWF:Ag concentration is less than 0.5, 0.6, or 0.7, the laboratory professional infers what VWF abnormality?

A

qualitative or type 2 VWD

227
Q

Low-dose RIPA is also called

A

ristocetin response curve

228
Q

ristocetin response curve is also called

A

Low-dose RIPA

229
Q

This test identifies subtype 2B

A

ristocetin response curve

230
Q

ristocetin response curve identifies what VWD?

A

subtype 2B

231
Q

The low-dose RIPA test is performed on what blood component?

A

Platelet Rich Plasma (PRP)

232
Q

What blood component is VWF:RCo assay performed on?

A

preserved platelet suspension

233
Q

A preserved platelet suspension is used to perform what assay?

A

VWF:RCo assay

234
Q

In subtype 2B the patient’s platelets agglutinate in response to how much ristocetin?

A

less than 0.5 mg/mL ristocetin / 0.1 mg/mL (sometimes)

235
Q

normal platelets agglutinate only at ristocetin concentrations of??

A

greater than 0.5 mg/mL

236
Q

platelets from a patient with this VWD may not agglutinate to ristocetin at all

A

subtype 2A

237
Q

VWF multimer analysis with this gel electrophoresis is a complex secondary confirmatory procedure that helps establish VWD type 2 and differentiates between VWD subtypes 2A, 2B, and perhaps 2M.

A

VWF multimer analysis by sodium dodecyl sulfate–polyacrylamide gel electrophoresis

238
Q

sodium dodecyl sulfate– polyacrylamide gel electrophoresis is a complex secondary confirmatory procedure that helps establish what VWD?

A

VWD type 2

239
Q

sodium dodecyl sulfate– polyacrylamide gel electrophoresis is a complex secondary confirmatory procedure that helps differentiate between what VWDs?

A

VWD subtypes 2A, 2B, and perhaps 2M.

240
Q

These VWDs lack high-molecular-weight multimers

A

both 2A and 2B

241
Q

intermediate multimers are presumed to be present in the electrophoretic pattern of what VWDs?

A

subtype 2B VWD

242
Q

What is presumed to be present in the electrophoretic pattern subtype 2B VWD but are absent from the pattern of a patient with subtype 2A VWD?

A

intermediate multimers

243
Q

In this type of VWD, the multimeric pattern appears to be normal despite the reduced function to concentration ratio.

A

type 2M

244
Q

This is available from specialized reference laboratories for differentiation of VWD type 2 subtypes.

A

Multimer analysis

245
Q

These influence VWF activity

A

(1) Varying genetic penetrance (2) ABO blood group (3) inflammation (4) hormones (5) age (6) physical stress

246
Q

Raised estrogen levels during what stages of pregnancy nearly normalize plasma VWF activity even in women with moderate VWF deficiency?

A

second and third trimesters

247
Q

This factor during the second and third trimesters of pregnancy nearly normalize plasma VWF activity even in women with moderate VWF deficiency

A

Raised estrogen levels

248
Q

These decrease rapidly after delivery

A

VWF concentration and function

249
Q

these medications raise VWF activity

A

Oral contraceptives and hormone replacement therapy

250
Q

VWF activity waxes and wanes with what?

A

with the menstrual cycle

251
Q

VWF activity decreases/rises substantially in acute inflammation such as occurs postoperatively, subsequent to trauma, or during an infection

A

Rises

252
Q

Physical stress such as cold, exertion, or a child’s crying or struggling during venipuncture causes VWF activity to rise/decrease

A

Rises

253
Q

What happens to the VWF activity when the phlebotomist allows the tourniquet to remain tied for more than 1 minute before venipuncture?

A

VWF activity rises

254
Q

What happens when the specimen is stored in the refrigerator before testing?

A

VWF descends

255
Q

What influences the RISE OF VWF ACTIVITY?

A

(1) Oral contraceptives (2) hormone replacement therapy (3) Acute inflammation (4) trauma (5) infection (6) Physical stress (7) cold (8) exertion (9) child’s crying (10) struggling during venipuncture (11) tied tourniquet for more than 1 minute

256
Q

In the United States proficiency surveys consistently reveal VWF:RCo assays to have an unimpressive interlaboratory coefficient of variation of what? and a least detectable activity range of what?

A

30%; 6% to 12%

257
Q

results of the VWF:RCo assay has led to development of what?

A

VWF collagen-binding (VWF:CB) assay

258
Q

VWF:CB employs what type of collagen as its solid-phase target antigen?

A

type III collagen

259
Q

What is the role of type III collagen in the VWF:CB?

A

It is its solid-phase target antigen

260
Q

When was VWF:CB assay developed?

A

1990

261
Q

VWF:CB assay produces results that more closely match those of what assay?

A

VWF:RCo assay

262
Q

Why does the VWF:CB assay produces results that more closely match those of VWF:RCo assay?

A

because collagen type III binds predominantly HMW-VWF multimers

263
Q

This requires standardization before VWF:CB assay achieves routine assay status

A

target collagen composition

264
Q

When collagen is standardized, this assay provides better precision than the VWF:RCo assay

A

VWF:CB assay

265
Q

This assay detects abnormalities of VWF collagen binding

A

VWF:CB assay

266
Q

This assay detects only abnormalities of VWF platelet GPIb binding

A

VWF:RCo, VWF:GPIbR, and VWF:GPIbM

267
Q

may improve assay sensitivity and precision when approved for clinical deployment

A

CLIA-based VWF:CB

268
Q

To reduce false-positive type 1 VWD diagnoses, the 2009 NHLBI VWD guidelines have coined the non-disease description of what?

A

“low VWF”

269
Q

This term is to describe the condition in which VWF activity and antigen concentrations are between 30% and 50% of normal

A

“low VWF”

270
Q

“low VWF” term is to describe the condition in which VWF activity and antigen concentrations between what?

A

30% and 50% of normal

271
Q

“Low VWF” in the ratio of VWF:RCo to VWF:Ag is greater than what?

A

greater than 0.5

272
Q

The FVIII activity of VWF:RCo to VWF:Ag with “Low VWF” patients is measured at…

A

greater than 50 units/dL

273
Q

What is the criteria to make a definite type 1 VWD diagnosis?

A

30% of normal VWF activity is used as the limit.

274
Q

These associate consistently with VWF levels less than 30%

A

VWF gene mutations

275
Q

linkages to a VWD appear in only half of instances when the VWF:Ag levels are what range?

A

30% to 50%

276
Q

VWD Interferences that cause false positives

A

Rheumatoid factor and heterophile antibodies

277
Q

Specimen mishandling such as prolonged tourniquet application, plasma refrigeration, filtration, or ultracentrifugation lead to what outcome?

A

false positives, false negatives, or false phenotypes

278
Q

the major determinant of bleeding risk is what?

A

low VWF

279
Q

VWF test result reference intervals are now based on what?

A

population based rather than ABO stratified

280
Q

What is The internationally generalized cutoff for LOW VWF?

A

50%

281
Q

What is The internationally generalized cutoff for VWD?

A

30%

282
Q

What is the reference interval of VWF by ABO of Type O?

A

36-157%

283
Q

What is the reference interval of VWF by ABO of Type A?

A

48-234%

284
Q

What is the reference interval of VWF by ABO of Type B?

A

57-241%

285
Q

What is the reference interval of VWF by ABO of Type AB?

A

64-238%

286
Q

Reference interval of Population based: “Low VWF”

A

<50%

287
Q

Reference interval of Population based: von Willebrand disease

A

<30%

288
Q

What is the athlete’s acronym for Mild bleeding?

A

Protection Rest Ice Compression Elevation (PRICE)

289
Q

Moderate bleeding may respond to what substances to trigger release of VWF from storage organelles?

A

estrogen and desmopressin acetate

290
Q

For VWD treatment, therapeutic dosages are monitored using what?

A

serial VWF:Ag assays

291
Q

this is an antidiuretic hormone analog used to control incontinence in diabetes mellitus and bedwetting

A

Desmopressin acetate

292
Q

What is the chemical component of Desmopressin acetate ?

A

1-desamino-8-D arginine vasopressin

293
Q

Desmopressin acetate is an antidiuretic hormone analog used to control what?

A

incontinence in diabetes mellitus and bedwetting

294
Q

What is a side effect of desmopressin acetate?

A

release of VWF from storage organelles

295
Q

What is Desmopressin acetate called in its ORAL FORM?

A

DDAVP, or oral spray form, Stimate

296
Q

What is the oral spay from of desmopressin acetate called?

A

Stimate

297
Q

This medication is consistently effective for type 1 and subtype 2M VWD and generally useful for subtype 2A.

A

Desmopressin acetate

298
Q

Desmopressin acetate is consistently effective for what types of VWD?

A

effective for type 1 and subtype 2M VWD and generally useful for subtype 2A.

299
Q

Desmopressin acetate is contraindicative of what VWD type?

A

subtype 2B

300
Q

Because of its THIS, repeated doses may lead to hyponatremia (low serum sodium)

A

antidiuretic property

301
Q

These inhibit fibrinolysis and may help control bleeding when used alone or in conjunction with desmopressin acetate.

A

e-aminocaproic acid (EACA) and tranexamic acid (TXA)

302
Q

Therapy using THIS preparation is preferred over human plasma-derived biologic therapy because nonbiologics eliminate the risk of viral disease transmission and circumvent religious objections to receipt of human blood products.

A

nonbiologic preparations

303
Q

For treatment of severe VWD (type 3) and subtype 2B, three commercially prepared human plasma-derived high purity preparations are available that provide a mixture of
VWF and coagulation FVIII:

A

Humate-P, Alphanate, and Wilate

304
Q

Humate-P, Alphanate, and Wilate are three three commercially prepared human plasma-derived high-purity preparations that are available for what VWD types?

A

Type 3 and Subtype 2B

305
Q

This is a recombinant VWF that provides no accompanying factor VIII.

A

Vonvendi

306
Q

The initial Vonvendi dose is HOW MUCH for HOW MANY HOURS?

A

40 to 80 IU/kg body weight every 8 to 24 hours

307
Q

Vonvendi is adjusted to the extent of what?

A

Vonvendi is adjusted to the extent of continued bleeding or the target VWF:Ag concentration.

308
Q

If the baseline factor VIII concentration is less than 40 IU/dL, physicians give recombinant VWF-free factor VIII within how many minutes?

A

within 10 minutes

309
Q

If the baseline factor VIII cocentration is less than 40 IU/dL, physicians give recombinant VWF-free factor VIII within 10 minutes of completing Vonvendi infusion at a ratio of WHAT?

A

1.3:1

310
Q

These concentrates contain no VWF and cannot be used to treat VWD.

A

Recombinant and affinity-purified factor VIII concentrates

311
Q

These blood components are less desirable alternatives because of the risk of virus transmission, and the necessary plasma volume per dose may cause TACO.

A

Cryoprecipitate and plasma

312
Q

Cryoprecipitate and plasma are less desirable alternatives because of the risk of virus transmission, and the necessary plasma volume per dose may cause WHAT?

A

TACO (Transfusion-associated circulatory overload)

CLIN CHEM 1 (LABORATORY) (2 decks)

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