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Coagulation cascade Flashcards

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1
Q

What is hemostasis?

A

The process of blood clot formation and dissolution

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2
Q

What does homeostasis require?

A

Platelet activation and a cascade of zymogens activation

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3
Q

4 phases of hemostasis

A

Constriction of blood vessel
Formation of a temporary “platelet plug”
Activation of the coagulation cascade
Fibrinolysis

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4
Q

Which steps are included in primary hemostasis?

A

Constriction of blood vessel
Formation of a temporary “platelet plug”
Activatio

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5
Q

Which step is included in secondary hemostasis?

A

Activation of the coagulation cascade

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6
Q

Which are the smallest cell in the blood?

A

Platelets

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7
Q

Where is the production of platelets?

A

Bone marrow

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8
Q

What is endothelin released by?

A

The endothelium

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9
Q

What layer of the blood vessel is destroyed during injury?

A

The endothelium layer

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10
Q

What causes platelet activation?

A

Collagen and basement membran exposure to blood

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11
Q

What does endothelin release cause?

A

Vasoconstriction

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12
Q

What are some of the signalling molecules released by platelets?

A

Thromboxanes

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13
Q

What allows adhesion of platelets to collagen?

A

Membran proteins like GPIb, GPIIB and GPIIIa

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14
Q

What is the coagulation cascade?

A

A series of reactions catalysed by protein enzymes known as coagulation factors

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15
Q

Why is blood coagulation a cascade?

A

A small trigger can have a bigger impact
It is very sensitive and effective

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16
Q

Is blood coagulation cascade regulated?

A

Yes highly
There are inhibitors which help with regulation

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17
Q

Are there more than one entry point?

A

Yes there are the intrinsic pathway and the extrinsic pathway

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18
Q

What is the extrinsic pathway triggered by?

A

Trauma

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19
Q

What is the intrinsic pathway triggered by?

A

Internal factors

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20
Q

Do the two pathways work independently?

A

Yes they can be triggered at the same time, both or just one

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21
Q

What surfaces are exposed upon future of the endothelial lining of the blood vessel?

A

The anionic surfaces

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22
Q

Example of coagulation factors

A

Fibrinogen
Prothrombin

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23
Q

Whatkind of enzymes are most of the coagulation factors?

A

Serine proteases

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24
Q

What is the final product of the coagulation cascade?

A

Cross-linked fibrin net

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25
What is the activated fibrinogen?
Fibrin
26
What activated fibrinogen?
Thrombin
27
Can thrombin also activate upstream?
Yes and it is called retrograde activation
28
Which is the only enzyme in the coagulation cascade that is not serine protease?
Fibrin-stabilizing factor which is Ca2+ dependent transglutaminase
29
What triggers the intrinsic pathway?
When factor XI is converted to factor XIa by thrombin
30
What converts fibrinogen into fibrin?
The proteolytic removal of amino acid residues
31
Is vitamin k essential for blood coagulation cascade?
Yes
32
What gets cleaved by thrombin?
The alpha and beta tails of fibrinogen
33
What does factor XIIIa do?
It binds, doesn't cleave Is activated by thrombin
34
What degrades fibrin when the clot is no longer needed?
The enzyme plasmin
35
Is plasminogen already incorporated in the clot?
Yes and is then activated by factors
36
2 conditions that cause blood coagulation cascade to go wrong
Hemophilia Thrombosis
37
What happens in thrombophilia?
Your blood clots more than in healthy individuals
38
What is haemophilia caused by a defect in?
Zymogen activation
39
What is a blood clot?
An Aggregate of specialised cell fragments which lack nuclei (platelets) cross-linked and stabilised by proteinaceous fibers consisting mainly of the protein fibrin
40
What are platelets?
Specialized cell fragments that lack nuclei
41
What is fibrin?
A protein
42
What is fibrin derived from?
The soluble zymogen fibrinogen
43
What are platelets differentiated by?
Hematropic cells
44
What does the shape change of platelets during platelet activation allow for?
Makes them able to bind to eachother
45
What shape does platelets change from and to?
Pancakes to more ball shape with protrusion
46
What kind of covalent modifications are made by th blood coagulation cascade, reversible or irreversible?
Irreversible
47
What are serine proteases?
Enzymes that cleave peptide bonds in proteins
48
What does serine serve as at the active site of the enzyme?
Nucleophilic amino acid
49
What is the main player in the catalytic mechanism in the serine proteases?
The catalytic triad
50
What does the catalytic triad consist of?
His 57 Ser 195 Asp 102
51
What converts fibrinogen to fibrin?
The proteolytic removal of amino acid residues
52
What does thrombin catalyse?
Peptide removal
53
What does factor XIIIa catalyse?
The formation of covalent cross-links between fibrins
54
What are gamma-carboxylated clotting proteins chelated to the membrane surface via?
Electrostatic interactions with calcium and negatively charged phospholipids of the platelet membrane
55
Is the activation of prothrombin fast or slow? and why
Slow because the activator cofactors are only present in small amounts
56
Which vitamin is essential for the process of clotting?
Vitamin K
57
What do vitamin K antagonists do?
They do not allow reduction of vitamin K
58
What converts fibrinogen to fibrin?
Thrombin
59
What is the precursor to Fibrin?
Fibrinogen
60
What can the fibrin monomers form when aggregated?
A soft clot
61
What stabalizes a soft clot?
Formation of amide bonds between the side chains of lysine and glutmine residues in different monomers
62
Which reactions cross-links fibrin monomers?
The transmutation reaction catalysed by factor XIIIa, transglutaminase
63
What ensures that clotting is regulated and limited to the site of injury?
Many mechanism: Some factors are unstable and lose activity quickly Clotting factors are diluted by blood flow Some factors are digested by protein C Protease inhibitors Heparin
64
What is protein C activated by?
Thrombin
65
What is heparin?
Anticoagulant found in mast cells
66
What does heparin do?
Helps inactivate serine protease clotting factors
67
When does heparin cofactor II inhibit thrombin?
In its procoagulant role
68
When does protein C inhibit thrombin/thrombomodulin complex?
When thrombin plays an anticoagulant role
69
What degrades fibrin?
Plasmin
70
Which enzyme are clots dissolved by?
Plasmin
71
What is Plasmin?
An enzyme
72
What is plasmin formed from?
Plasminogen
73
What catalyses the reaction where plasminogen is made into plasmin?
Tissue-type plasminogen activator (TPA)
74
What does fibrinolysis involve?
Degradation of fibrin in a clot by plasmin
75
What kind of enzyme is plasmin?
Serine protease
76
What can activate plasminogen?
Tissue plasminogen activator Urokinase
77
What is haemophilia?
Increased tendency to bleed
78
What causes haemophilia?
An abnormality of a blood-clotting factor Defect in zymogen activation
79
Which is the major form of haemophilia?
Haemophilia A
80
What is haemophilia a caused by?
A defect of clotting factor VIII
81
What tests the intrinsic pathway?
Activated partial thromboplastin time
82
What tests the extrinsic pathway?
Prothrombin time
83
What tests the final common pathway?
Thrombin clotting time
84
What does aspirin block the formation of?
Thromboxane
85
What is heparan sulfate?
A heparin-like polysaccharide but attached to proteins
86
Which are the highest negative-charge density biomolecules?
Heparin Heparin sulfate
87
How does heparin and heparin sulfate prevent blood clotting?
By activating protease inhibitor antithrombin
88
What happens when heparin and heparin sulfate binds to viruses and bacteria?
decreases their virulence
89
What does warfarin inhibit?
Vitamin K production
90
Different name for thrombin
Factor 2
91
Is fibrin soluble or insoluble in blood plasma?
Insoluble

Biochemistry (28 decks)

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