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Year 1: Cardiovascular System > 9. Basic Haemostasis > Flashcards

9. Basic Haemostasis Flashcards

1
Q

What are the functions of haemostasis?

A

Prevention of blood loss from intact vessels

Arrest of bleeding from injured vessels

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2
Q

What does the formation of an unstable platelet plug involve?

A

Platelet adhesion and platelet aggregation

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3
Q

What does the stabilisation of the platelet plug involve?

A

Activation of the blood coagulation and fibrin

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4
Q

What are the stages of haemostasis?

A

Primary and secondary

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5
Q

What happens in the initial response?

A

Platelets identify endothelial damage and forms a clump

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6
Q

What follows the initial response?

A

Coagulation takes place and is accelerated by the platelets

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7
Q

Define coagulation

A

The process by which blood is converted from a liquid to a solid state

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8
Q

What is Von Willebrand factor?

A

A plasma protein secreted by endothelial cells and platlets. It binds to collagen and attracts platelets

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9
Q

When the endothelial layer is damaged what is revealed?

A

The subendothelial layer which is rich in collagen

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10
Q

How is collagen recognised?

A

1) Von willebrand factor

2) Glycoprotein 1a Receptor on the platelets binds directly to the collagen

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11
Q

How do platelets bind to the von willebrand factor?

A

Via glycoprotein 1b receptor on the von willebrand factor

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12
Q

What method of recognising collagen is favoured in small blood vessels?

A

There could be high shear stress in small blood vessels, favouring the von willebrand mechanism

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13
Q

When do the platelets become active?

A

When the glycoprotein receptors on the platelets are engaged either to the Von Willebrand Factor or directly to the collagen

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14
Q

What is released when the platelets are active?

A

ADP and Prostaglandins (thromboxane)

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15
Q

What does fibrinogen bind to?

A

Activated platelets with available glycoproteins IIb and IIIa

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16
Q

What protease can also directly activate the platelets?

A

Thrombin

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17
Q

When platelets become activated how do they change?

A

They change their shape and hence their membrane composition.
There is a change in phospholipids and presentation of new proteins (GlpIIb + GlpIIIa)

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18
Q

Where are most clotting factors made?

A

Liver

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19
Q

Where is the Von Willebrand factor made?

A

Endothelial Cells

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20
Q

What are the precursors of platelets?

A

Megakaryocytes

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21
Q

What do megakaryocytes synthesise?

A

Factor V

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22
Q

Define Zymogen

A

an inactive substance (protease) which is converted into an enzyme when activated by another enzyme

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23
Q

What is the first zymogen in the clotting cascade?

A

Factor XII

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24
Q

What is factor XII converted to?

A

XIIa (active)

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25
Q

What does factor XIIa do?

A

It converts factor XI to XIa

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26
Q

What is factor XIa do?

A

It converts factor IX to IXa

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27
Q

What does the intrinsic pathway involve?

A

The activation of a zymogen and binding of coagulation factors to the activated platelet

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28
Q

What is factor IXa do?

A

It converts factor X to factor Xa with factor VIIIa on a platelet phospholipid membrane

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29
Q

What is factor X converted to?

A

Factor Xa

30
Q

What converted factor X to factor Xa?

A

Factor, IXa, Factor VIIIa and the platelet phospholipid membrane

31
Q

What is factor VIII

A

A Cofactor

32
Q

What is tissue factor?

A

A membrane protein which isn’t normally found in the blood

33
Q

What is the function of tissue factor?

A

It is a potent activator of the clotting cascade.

34
Q

What does tissue factor bind to?

A

It binds to factor VII converting it to factor VIIa

35
Q

What is the function of factor VIIa?

A

It converts factor X to factor Xa and factor IX to factor IXa

36
Q

What does the extrinsic pathway involve?

A

Tissue factor and Factor VII

37
Q

What is the function of factor Xa?

A

Converts prothrombin to thrombin (Factor V is required)

38
Q

What does thrombin do to the platelet?

A

It further activates its forming a fibrin clot

39
Q

What helps convert prothrombin to thrombin faster?

A

Factor Va

40
Q

What converts Factor V to Factor Va?

A

Trace amounts of thrombin

41
Q

What does thrombin do?

A

Converts fibrinogen (soluble) to fibrin forming a fibrin clot

42
Q

What is the fibrin clot cross linked by?

A

Factor XIIIa

43
Q

What is point of cross linking?

A

So the fibrin clot is stabilised and can’t be broken down by shear forces

44
Q

What are the three pathways in the clotting cascade?

A

Intrinsic
Extrinsic
Common Pathway

45
Q

What is the physiological initiator of coagulation?

A

Tissue factor hence the extrinsic pathway is the main driver of coagulation and heamostasis

46
Q

What is factor XII mainly used for?

A

In vitro reactions

47
Q

Where is tPA made?

A

Endothelial cells. It is usually quite low and made locally next to where the clot forms

48
Q

What is tPA?

A

Tissue Plasminogen Activator

49
Q

What is the role of tPA?

A

Converts plasminogen from an inactive zymogen to an active protease (plasmin)

50
Q

Where does tPA catalyse its reaction?

A

On a fibrin clot that assembles the tPA and plasminogen on its surface

51
Q

What is plasmin?

A

A powerful proteolytic enzyme that can break down the fibrin clot

52
Q

What are the breakdown products of the fibrin clot?

A

Fibrin degradation products

53
Q

What is measured during thrombolytic therapy?

A

FDP

54
Q

What is used for the therapeutic thrombolysis for myocardial infarction?

A

tPA and Streptokinase

55
Q

Why doesn’t blood clot completely whenever clotting is initiated?

A

Coagulation inhibitory mechanisms

56
Q

What are the two coagulation inhibitory mechanisms?

A

Direct inhibition

Indirect inhibition

57
Q

What is the mechanism of direct inhibition?

A

Direct inhibition of the activated coagulation factors

58
Q

What is an example of a direct inhibitor?

A

Antithrombin

59
Q

What can antithrombin inhibit?

A

XIa
IXa
Xa
thrombin

60
Q

What is the mechanism of indirect inhibition?

A

Mechanism which slows down the amount of thrombin that is generated. Protein C must be activated in the protein C anticoagulant pathway

61
Q

What does a reduction in antithrombin cause?

A

A higher risk of thrombosis

62
Q

What accelerates the action of antithrombin?

A

Heparin

63
Q

What is used for the immediate anticoagulation in venous thrombosis and pulmonary embolism?

A

Heparin

64
Q

What is the mechanism of action for protein C?

A

It inactivates cofactors (factor VIII and V)

65
Q

When coagulation inhibitory mechanisms fail there is an increased risk of…

A

Thrombosis

66
Q

What failures of coagulation inhibitory mechanisms are there?

A

1) Antithrombin deficiency
2) Protein C deficiency
3) Protein S deficiency
4) Factor V Leiden

67
Q

How many times do factor 8 and factor 5 accelerate thrombin formation?

A

10,000 fold

68
Q

What protein can thrombin bind to on the surface of the endothelium?

A

Thrombomodulin

69
Q

What happens to the thrombin when it binds to thrombomodulin?

A

It changes conformation and activates protein C and S

70
Q

What is factor V Leiden

A

A common polymorphism resulting in an amino acid change in factor V meaning it cannot be inactivated.

71
Q

What does thrombin normally do?

A

Form the clot, activate the platelets and activate factor VIII and V

Year 1: Cardiovascular System (21 decks)

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