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Biochemistry > Coagulation cascade > Flashcards

Coagulation cascade Flashcards

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
Q

What is the activated fibrinogen?

A

Fibrin

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26
Q

What activated fibrinogen?

A

Thrombin

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27
Q

Can thrombin also activate upstream?

A

Yes and it is called retrograde activation

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28
Q

Which is the only enzyme in the coagulation cascade that is not serine protease?

A

Fibrin-stabilizing factor which is Ca2+ dependent transglutaminase

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29
Q

What triggers the intrinsic pathway?

A

When factor XI is converted to factor XIa by thrombin

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30
Q

What converts fibrinogen into fibrin?

A

The proteolytic removal of amino acid residues

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31
Q

Is vitamin k essential for blood coagulation cascade?

A

Yes

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32
Q

What gets cleaved by thrombin?

A

The alpha and beta tails of fibrinogen

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33
Q

What does factor XIIIa do?

A

It binds, doesn’t cleave
Is activated by thrombin

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34
Q

What degrades fibrin when the clot is no longer needed?

A

The enzyme plasmin

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35
Q

Is plasminogen already incorporated in the clot?

A

Yes and is then activated by factors

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36
Q

2 conditions that cause blood coagulation cascade to go wrong

A

Hemophilia
Thrombosis

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37
Q

What happens in thrombophilia?

A

Your blood clots more than in healthy individuals

38
Q

What is haemophilia caused by a defect in?

A

Zymogen activation

39
Q

What is a blood clot?

A

An Aggregate of specialised cell fragments which lack nuclei (platelets) cross-linked and stabilised by proteinaceous fibers consisting mainly of the protein fibrin

40
Q

What are platelets?

A

Specialized cell fragments that lack nuclei

41
Q

What is fibrin?

A

A protein

42
Q

What is fibrin derived from?

A

The soluble zymogen fibrinogen

43
Q

What are platelets differentiated by?

A

Hematropic cells

44
Q

What does the shape change of platelets during platelet activation allow for?

A

Makes them able to bind to eachother

45
Q

What shape does platelets change from and to?

A

Pancakes to more ball shape with protrusion

46
Q

What kind of covalent modifications are made by th blood coagulation cascade, reversible or irreversible?

A

Irreversible

47
Q

What are serine proteases?

A

Enzymes that cleave peptide bonds in proteins

48
Q

What does serine serve as at the active site of the enzyme?

A

Nucleophilic amino acid

49
Q

What is the main player in the catalytic mechanism in the serine proteases?

A

The catalytic triad

50
Q

What does the catalytic triad consist of?

A

His 57
Ser 195
Asp 102

51
Q

What converts fibrinogen to fibrin?

A

The proteolytic removal of amino acid residues

52
Q

What does thrombin catalyse?

A

Peptide removal

53
Q

What does factor XIIIa catalyse?

A

The formation of covalent cross-links between fibrins

54
Q

What are gamma-carboxylated clotting proteins chelated to the membrane surface via?

A

Electrostatic interactions with calcium and negatively charged phospholipids of the platelet membrane

55
Q

Is the activation of prothrombin fast or slow? and why

A

Slow because the activator cofactors are only present in small amounts

56
Q

Which vitamin is essential for the process of clotting?

A

Vitamin K

57
Q

What do vitamin K antagonists do?

A

They do not allow reduction of vitamin K

58
Q

What converts fibrinogen to fibrin?

A

Thrombin

59
Q

What is the precursor to Fibrin?

A

Fibrinogen

60
Q

What can the fibrin monomers form when aggregated?

A

A soft clot

61
Q

What stabalizes a soft clot?

A

Formation of amide bonds between the side chains of lysine and glutmine residues in different monomers

62
Q

Which reactions cross-links fibrin monomers?

A

The transmutation reaction catalysed by factor XIIIa, transglutaminase

63
Q

What ensures that clotting is regulated and limited to the site of injury?

A

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
Q

What is protein C activated by?

A

Thrombin

65
Q

What is heparin?

A

Anticoagulant found in mast cells

66
Q

What does heparin do?

A

Helps inactivate serine protease clotting factors

67
Q

When does heparin cofactor II inhibit thrombin?

A

In its procoagulant role

68
Q

When does protein C inhibit thrombin/thrombomodulin complex?

A

When thrombin plays an anticoagulant role

69
Q

What degrades fibrin?

A

Plasmin

70
Q

Which enzyme are clots dissolved by?

A

Plasmin

71
Q

What is Plasmin?

A

An enzyme

72
Q

What is plasmin formed from?

A

Plasminogen

73
Q

What catalyses the reaction where plasminogen is made into plasmin?

A

Tissue-type plasminogen activator (TPA)

74
Q

What does fibrinolysis involve?

A

Degradation of fibrin in a clot by plasmin

75
Q

What kind of enzyme is plasmin?

A

Serine protease

76
Q

What can activate plasminogen?

A

Tissue plasminogen activator
Urokinase

77
Q

What is haemophilia?

A

Increased tendency to bleed

78
Q

What causes haemophilia?

A

An abnormality of a blood-clotting factor
Defect in zymogen activation

79
Q

Which is the major form of haemophilia?

A

Haemophilia A

80
Q

What is haemophilia a caused by?

A

A defect of clotting factor VIII

81
Q

What tests the intrinsic pathway?

A

Activated partial thromboplastin time

82
Q

What tests the extrinsic pathway?

A

Prothrombin time

83
Q

What tests the final common pathway?

A

Thrombin clotting time

84
Q

What does aspirin block the formation of?

A

Thromboxane

85
Q

What is heparan sulfate?

A

A heparin-like polysaccharide but attached to proteins

86
Q

Which are the highest negative-charge density biomolecules?

A

Heparin
Heparin sulfate

87
Q

How does heparin and heparin sulfate prevent blood clotting?

A

By activating protease inhibitor antithrombin

88
Q

What happens when heparin and heparin sulfate binds to viruses and bacteria?

A

decreases their virulence

89
Q

What does warfarin inhibit?

A

Vitamin K production

90
Q

Different name for thrombin

A

Factor 2

91
Q

Is fibrin soluble or insoluble in blood plasma?

A

Insoluble

Biochemistry (28 decks)

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