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[Hematology 2] Lec > THE COAGULATION CASCADE > Flashcards

THE COAGULATION CASCADE Flashcards

1
Q

All components are found in the [?].

A

circulating blood

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2
Q

To be activated, the blood must have direct contact with a foreign object such as a [?].

A

damaged blood vessel or glass

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3
Q

This results to absorption of [?] to the negatively- charged collagen exposed by vessel wall damage.

A

XII

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4
Q
  1. [?] is activated by the foreign material into [?]
A

Factor XII

XIIa

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5
Q
  1. [?] reacts weakly with [?], thus converting them into their forms
A

XIla

XI, prekallikrein (also by XIIf), and plasminogen

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6
Q

• Formed kallikrein feeds back to [?] and causes enzymatic cleavage producing more [?].

A

XII

XIla

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7
Q
  1. Xla in the presence of Ca** activates [?]
A

IX

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8
Q

• Note: IX can also be activated by [?]:
(CURRENT CONCEPT OF COAGULATION)

A

VIla-Ca*-TF complex

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9
Q
  1. IXa in the presence of [?] activates Х.
A

Catt, platelet phospholipids, and Villa

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10
Q

[?] is necessary for the activation of this system.

A

TISSUE FACTOR

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11
Q

All cells with the possible exception of those in the blood, contain [?].

A

tissue factor

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12
Q

When injury occurs, the [?] is released and acts as a cofactor in initiating coagulation.

A

tissue factor

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13
Q

The released [?] binds to VII and activates it to VIla.

A

tissue factor

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14
Q

Then [?] activates X to Xa of the common pathway.

A

VIla , together with calcium,

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15
Q

Begins with activation of factor X via the Intrinsic Pathway (?) or via the Extrinsic Pathway (?) to form Prothrombinase/[?].

A

IXaVIlla-Ca++-PL

VIla-Ill-Ca++

Xa-Va-Ca++-PPL

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16
Q

This prothrombinase complex converts [?] to thrombin which then cleaves [?] into fibrin.

A

prothrombin

fibrinogen

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17
Q

Conversion of Fibrinogen to Fibrin: STEPS:
1. Thrombin cleaves the a and B chains only (releasing [?]) forming soluble fibrin monomer/unstable gel.
2. Fibrin monomers aggregate spontaneously end to end, side to side to form soluble fibrin polymers thus vulnerable to enzyme [?] (also soluble in [?]).
3. [?] crosslinks adjacent fibrin monomers by forming COVALENT bonds to form stable and insoluble clot

A

fibrinopeptides A and B

plasmin; 5M urea

Factor XIII: XIlla + Ca++

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18
Q

What activates factor XIII to XIIIa?

A

Thrombin or Collagen

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19
Q

The key initiating step is the exposure of TF to the circulation and reaction of [?].

A

TF with factor VII

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20
Q

The [?] can enzymatically activate factors X and IX.

A

TF-factor/VIla complex

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21
Q

The initial activation of factor X to Xa may be important in getting the coagulation cascade started, however, tissue factor pathway inhibitor (TFP) rapidly inactivates the [?].

A

TF-VIla-Xa complex

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22
Q

The major action of the TFVIla complex in vivo is the activation of [?], which then activates [?].

A

factor IX to IXa

factor X to Xa

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23
Q

Consequently, [?] is converted to thrombin, then [?] is converted to fibrin.

A

prothrombin

fibrinogen

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24
Q

Factors [?] have positive feedback activity on earlier steps of the cascade

A

Xa and IIa

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25
Q

Activation of Coagulation
• It is [?]

A

autocatalytic or self-perpetuating

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26
Q

• Low level of thrombin activates [?] and [?]; Induces [?]

A

V and VIII

XIlI and XI

platelet aggregation

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27
Q

Inhibitor to Coagulation
• Controls

A

excessive coagulation

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28
Q

• Increase concentration of thrombin; destroys [?]; activates [?]

A

V and VIII

Protein C

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29
Q

increase plasminogen activation

A

Protein C and S

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30
Q

Promote plasmin generation (fibrinolysis)

A

Thrombin

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31
Q

: activates VIII to VIIIa

A

Factor II, X, residual thrombin (low level)

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32
Q

: activates FV

A

Thrombin, residual thrombin (low level)

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33
Q

: inhibits FV and VIII

A

residual thrombin (high level)

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34
Q
  • regulatory mechanism to stop the cascade
A

inhibits FV and VIII

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35
Q
  • continuous activation slows down the cascade
A

inhibits FV and VIII

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36
Q
  • Thrombin is a very powerful protein that can activate many factor (FIX, FVII, FXIII)
A

inhibits FV and VIII

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37
Q
  • to stop intrinsic pathway from accessing FX; FX will not be able to activate another thrombin/prothrombin to become thrombin
A

inhibits FV and VIII

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38
Q

: - forms soluble fibrin to insoluble fibrin

A

Fibrin XIIIa

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39
Q
  • stabilizes the clot
A

Fibrin XIIIa

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40
Q
  • soluble clot only forms fibrin meshwork (does not activate)
A

Fibrin XIIIa

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41
Q

may activate XII to XIIa

A

FXII + negative surface, Platelet

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42
Q

: procoagulant

A

Platelet

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43
Q

activates prekallikrein to kallikrein

A

FXII

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44
Q

activates HMWK to kinin (for the release of bradykinin. w/c participates in inflammation and pain cessation)

A

Kallikrein

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45
Q

activated form of HMW

A

kinin

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46
Q

uses HMWK as a cofactor to activate more FXII (feedback; autocatalytic with XII to XIIa)

A

Kallikrein

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47
Q

activates plasminogen to plasmin

A

XIII and Kallikrein

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48
Q

(fibrinolysis and hemostasis occur simultaneously making [?] both procoagulant and profibrinolysis)

A

XII

49
Q

works on fibrinolysis (dissolution of clot) and complement system (allergic-mediated reactions)

A

Plasmin

50
Q

Feedback to XII

A

Plasmin

51
Q

Product: fragmentation of XII

A

Plasmin

52
Q

Activation of XII by negative surface or exposed collagen

A

Plasmin

53
Q

activates FXI (end of contact phase)

A

FXII and Kallikrein

54
Q

: form low level of residual thrombin existing in the circulation

A

VIIIa of intrinsic tenase

55
Q

Only happens in vivo (glass tubes does not have TF, only from the blood vessels)

A

EXTRINSIC System / TISSUE FACTOR Pathway

56
Q

is released from a damaged blood vessel

A

TF

57
Q

: activates prothromnbin (II) to thrombin

A

Prothrombinase

58
Q

: from low level of residual thrombin existing outside coagulation’ activated by platelet

A

Va of prothrombinase

59
Q

: cleaves and breaks fibrinogen to make fibrin clot

A

Thrombin

60
Q

: splits into fibronopeptide A to fibrinopeptide B

A

Fibrin (soluble)

61
Q

(very soluble; can only be stabilized by XIIIa to make cross-link fibrin clot)

A

fibronopeptide A to fibrinopeptide B

62
Q

XIIIa is activated by

A

thrombin

63
Q

thrombin At low level: amplifies [?] (from coagulation)

A

V and VIII activation

64
Q

Activates prothrombinase (+ X and Va) – prothrombinase becomes autocatalytic when activated by level thrombin (independent activation from intrinsic or extrinsic)

A

Thrombin

65
Q

FXI activation and Plasminogen activation

A

Thrombin

66
Q

[?] is activated by both extrinsic and intrinsic pathway resulting to [?].

A

X

high level of thrombin

67
Q

As a result, TFPI keeps thrombin in low level by inhibiting [?] from activating [?]

A

TF-VII

X

68
Q

VIIa/TF complex activates

A

IX and X

69
Q

-Principal regulator of TF pathway/extrinsic pathway

A

TFPI

70
Q

-Kunitz type of inhibitor/TFPI:

A

Kunitz-1 and Kuntiz-2

71
Q

Synthesized by EC and expressed in platelets

A

TFPI

72
Q

TFPI Mode of action: two step process

A
  1. TFPI binds to FX= TFPI:Xa
  2. TFPI:Xa binds to TF:VII
  3. TFPI binds to TF-VII-Xa complex (alternative)
73
Q

: type of inhibitor that can inhibit 2 or more substances at once

A

Kunitz

74
Q

: inactivates TF-VIIa complex

A

Kunitz-1

75
Q

: inactivates Xa

A

Kuntiz-2

76
Q

Xa is inactivated and can no longer bind to other coagulation factors

A
  1. TFPI binds to FX= TFPI:Xa
77
Q
  1. TFPI binds to FX= TFPI:Xa
A

Kuntiz-2

78
Q
  1. TFPI:Xa binds to TF:VII
A

Kuntiz-1

79
Q
  1. TFPI binds to TF-VII-Xa complex (alternative)
A

Kuntiz-1 and Kuntiz-2

80
Q

TFPI cofactor

A

Protein S

81
Q

Cofactor of TFPI in deactivating Xa or TF-VIIa complex

Deactivation of extrinsic pathway (TF-VIIa complex)

A

Protein S

82
Q

are still activated and targets FIX

A

TF and VII (zymogen)

83
Q

Coagulation shifts to

A

intrinsic pathway

84
Q

Inhibition of extrinsic pathway =[?] level of thrombin ([?]to V and VIII and [?] fibrinolysis by activating plasminogen to plasmin; bleeding injury = [?]; body adjusts coagulation w/ ↓ level of thrombin)

A

↓

destructive

initiates

more coagulation

85
Q

TFPI keeps thrombin in

A

low levels

86
Q

: cannot produce clot; deactivates V and VIII; initiates plasminogen to plasmin instead of fibrinogen to fibrin (TFPI makes coagulation possible)

A

High levels of thrombin

87
Q

Cofactor of Thrombin during activation of plasminogen to plasmin

A

Protein S

88
Q

When Xa is activated: it becomes a [?] (twice activation; 2x times more potent)

A

double chain

89
Q

activates X to Xa (triple chain)

A

VII

90
Q

activates VII to VIIa (double chain)

A

Xa

91
Q
  1. TF is exposed to [?]
  2. TF reacts [?] and activates it.
  3. TF/VIla → [?]
A

damaged endothelium

w/FVII

FX to FXa

92
Q
  • Low level of thrombin
A

ACTIVATOR

93
Q

INHIBITOR

A
  • High level of thrombin
94
Q

-Enhances prothrombinase → self-perpetuating/independent

A

ACTIVATOR

95
Q

-Activates FV (previously activated by paltelets) and VIII (previously activated by residual thrombin)

A

ACTIVATOR

96
Q

-Activates FXIII

A

ACTIVATOR

97
Q

-Activate platelets

A

ACTIVATOR

98
Q

-Induce plt aggregation

A

ACTIVATOR

99
Q

-Inhibit FV and VIll

A

INHIBITOR

100
Q

-Initiate fibrinolysis (activates plasminogen)

A

INHIBITOR

101
Q
  • Activates Protein C (anticoagulant)
A

INHIBITOR

102
Q

activation of II to IIa by [?] = thrombin activates on its own w/o intrinsic/extrinsic pathway

A

prothrombinase

103
Q

side reaction to cross-link soluble fibrinopeptdies

A

FXIII

104
Q

activators of platelet:

A

collagen and ↓ thrombin

105
Q

Activators of plasminogen

A

Thrombin, Protein S, Protein Z, Thrombomodulin

106
Q

Also inactivates V and VIII

A

Protein C (anticoagulant)

107
Q

Enhances plasmin

A

Protein C (anticoagulant)

108
Q

TFPI deficiency: [?] activation; [?] (inactivating V and VIII and initiating fibrinolysis); [?] due to preactivation of plasminogen to plasmin = [?]

A

↑Xa

↑thrombin

no coagulation

PROLONGED BLEEDING

109
Q

-Perpetuate FXII activation

A

KALLIKREIN

110
Q

-Initiates the kinin system

A

KALLIKREIN

111
Q

-Initiates fibrinolytic and complement system (w/FXII)

A

KALLIKREIN

112
Q

-Activates FXI

A

KALLIKREIN

113
Q

uses HMWK as a cofactor to produce more FXII

A

KALLIKREIN

114
Q

can feedback to FXII by fragmenting it (production, not activation, of FXII)

A

Plasmin

115
Q

Activates HMWK to kinin (produces bradykinin)

A

KALLIKREIN

116
Q

Fibrinolytic: [?] activates plasminogen to plasmin

A

K and XII

117
Q

Side reaction of activating XI to XIa

A

KALLIKREIN

118
Q
  • Activates prothrombin
A

STUART PROWER (Factor X)

119
Q
  • Hydrolyze FVII → double chain (85x more procoagulant activity)
A

STUART PROWER (Factor X)

[Hematology 2] Lec (29 decks)

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