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Hematology 2 Lec > THE COAGULATION CASCADE > Flashcards

THE COAGULATION CASCADE Flashcards

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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
Activation of Coagulation • It is [?]
autocatalytic or self-perpetuating
26
• Low level of thrombin activates [?] and [?]; Induces [?]
V and VIII XIlI and XI platelet aggregation
27
Inhibitor to Coagulation • Controls
excessive coagulation
28
• Increase concentration of thrombin; destroys [?]; activates [?]
V and VIII Protein C
29
increase plasminogen activation
Protein C and S
30
Promote plasmin generation (fibrinolysis)
Thrombin
31
: activates VIII to VIIIa
Factor II, X, residual thrombin (low level)
32
: activates FV
Thrombin, residual thrombin (low level)
33
: inhibits FV and VIII
residual thrombin (high level)
34
- regulatory mechanism to stop the cascade
inhibits FV and VIII
35
- continuous activation slows down the cascade
inhibits FV and VIII
36
- Thrombin is a very powerful protein that can activate many factor (FIX, FVII, FXIII)
inhibits FV and VIII
37
- to stop intrinsic pathway from accessing FX; FX will not be able to activate another thrombin/prothrombin to become thrombin
inhibits FV and VIII
38
: - forms soluble fibrin to insoluble fibrin
Fibrin XIIIa
39
- stabilizes the clot
Fibrin XIIIa
40
- soluble clot only forms fibrin meshwork (does not activate)
Fibrin XIIIa
41
may activate XII to XIIa
FXII + negative surface, Platelet
42
: procoagulant
Platelet
43
activates prekallikrein to kallikrein
FXII
44
activates HMWK to kinin (for the release of bradykinin. w/c participates in inflammation and pain cessation)
Kallikrein
45
activated form of HMW
kinin
46
uses HMWK as a cofactor to activate more FXII (feedback; autocatalytic with XII to XIIa)
Kallikrein
47
activates plasminogen to plasmin
XIII and Kallikrein
48
(fibrinolysis and hemostasis occur simultaneously making [?] both procoagulant and profibrinolysis)
XII
49
works on fibrinolysis (dissolution of clot) and complement system (allergic-mediated reactions)
Plasmin
50
Feedback to XII
Plasmin
51
Product: fragmentation of XII
Plasmin
52
Activation of XII by negative surface or exposed collagen
Plasmin
53
activates FXI (end of contact phase)
FXII and Kallikrein
54
: form low level of residual thrombin existing in the circulation
VIIIa of intrinsic tenase
55
Only happens in vivo (glass tubes does not have TF, only from the blood vessels)
EXTRINSIC System / TISSUE FACTOR Pathway
56
is released from a damaged blood vessel
TF
57
: activates prothromnbin (II) to thrombin
Prothrombinase
58
: from low level of residual thrombin existing outside coagulation’ activated by platelet
Va of prothrombinase
59
: cleaves and breaks fibrinogen to make fibrin clot
Thrombin
60
: splits into fibronopeptide A to fibrinopeptide B
Fibrin (soluble)
61
(very soluble; can only be stabilized by XIIIa to make cross-link fibrin clot)
fibronopeptide A to fibrinopeptide B
62
XIIIa is activated by
thrombin
63
thrombin At low level: amplifies [?] (from coagulation)
V and VIII activation
64
Activates prothrombinase (+ X and Va) – prothrombinase becomes autocatalytic when activated by level thrombin (independent activation from intrinsic or extrinsic)
Thrombin
65
FXI activation and Plasminogen activation
Thrombin
66
[?] is activated by both extrinsic and intrinsic pathway resulting to [?].
X high level of thrombin
67
As a result, TFPI keeps thrombin in low level by inhibiting [?] from activating [?]
TF-VII X
68
VIIa/TF complex activates
IX and X
69
-Principal regulator of TF pathway/extrinsic pathway
TFPI
70
-Kunitz type of inhibitor/TFPI:
Kunitz-1 and Kuntiz-2
71
Synthesized by EC and expressed in platelets
TFPI
72
TFPI Mode of action: two step process
1. TFPI binds to FX= TFPI:Xa 2. TFPI:Xa binds to TF:VII 3. TFPI binds to TF-VII-Xa complex (alternative)
73
: type of inhibitor that can inhibit 2 or more substances at once
Kunitz
74
: inactivates TF-VIIa complex
Kunitz-1
75
: inactivates Xa
Kuntiz-2
76
Xa is inactivated and can no longer bind to other coagulation factors
1. TFPI binds to FX= TFPI:Xa
77
1. TFPI binds to FX= TFPI:Xa
Kuntiz-2
78
2. TFPI:Xa binds to TF:VII
Kuntiz-1
79
3. TFPI binds to TF-VII-Xa complex (alternative)
Kuntiz-1 and Kuntiz-2
80
TFPI cofactor
Protein S
81
Cofactor of TFPI in deactivating Xa or TF-VIIa complex Deactivation of extrinsic pathway (TF-VIIa complex)
Protein S
82
are still activated and targets FIX
TF and VII (zymogen)
83
Coagulation shifts to
intrinsic pathway
84
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)
↓ destructive initiates more coagulation
85
TFPI keeps thrombin in
low levels
86
: cannot produce clot; deactivates V and VIII; initiates plasminogen to plasmin instead of fibrinogen to fibrin (TFPI makes coagulation possible)
High levels of thrombin
87
Cofactor of Thrombin during activation of plasminogen to plasmin
Protein S
88
When Xa is activated: it becomes a [?] (twice activation; 2x times more potent)
double chain
89
activates X to Xa (triple chain)
VII
90
activates VII to VIIa (double chain)
Xa
91
1. TF is exposed to [?] 2. TF reacts [?] and activates it. 3. TF/VIla → [?]
damaged endothelium w/FVII FX to FXa
92
- Low level of thrombin
ACTIVATOR
93
INHIBITOR
- High level of thrombin
94
-Enhances prothrombinase → self-perpetuating/independent
ACTIVATOR
95
-Activates FV (previously activated by paltelets) and VIII (previously activated by residual thrombin)
ACTIVATOR
96
-Activates FXIII
ACTIVATOR
97
-Activate platelets
ACTIVATOR
98
-Induce plt aggregation
ACTIVATOR
99
-Inhibit FV and VIll
INHIBITOR
100
-Initiate fibrinolysis (activates plasminogen)
INHIBITOR
101
- Activates Protein C (anticoagulant)
INHIBITOR
102
activation of II to IIa by [?] = thrombin activates on its own w/o intrinsic/extrinsic pathway
prothrombinase
103
side reaction to cross-link soluble fibrinopeptdies
FXIII
104
activators of platelet:
collagen and ↓ thrombin
105
Activators of plasminogen
Thrombin, Protein S, Protein Z, Thrombomodulin
106
Also inactivates V and VIII
Protein C (anticoagulant)
107
Enhances plasmin
Protein C (anticoagulant)
108
TFPI deficiency: [?] activation; [?] (inactivating V and VIII and initiating fibrinolysis); [?] due to preactivation of plasminogen to plasmin = [?]
↑Xa ↑thrombin no coagulation PROLONGED BLEEDING
109
-Perpetuate FXII activation
KALLIKREIN
110
-Initiates the kinin system
KALLIKREIN
111
-Initiates fibrinolytic and complement system (w/FXII)
KALLIKREIN
112
-Activates FXI
KALLIKREIN
113
uses HMWK as a cofactor to produce more FXII
KALLIKREIN
114
can feedback to FXII by fragmenting it (production, not activation, of FXII)
Plasmin
115
Activates HMWK to kinin (produces bradykinin)
KALLIKREIN
116
Fibrinolytic: [?] activates plasminogen to plasmin
K and XII
117
Side reaction of activating XI to XIa
KALLIKREIN
118
- Activates prothrombin
STUART PROWER (Factor X)
119
- Hydrolyze FVII → double chain (85x more procoagulant activity)
STUART PROWER (Factor X)

Hematology 2 Lec (29 decks)

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