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Haematology Y2 > Haemostasis > Flashcards

Haemostasis Flashcards

1
Q

What 2 problems can abnormal haemostats cause

A
  1. Bleeding disorders

2. Thrombosis

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2
Q

4 steps in the response to injury of endothelial lining

A

Vessel constriction
Formation of an unstable platelet plug
Stabilisation of the plug with fibrin
Vessel repair and dissolution of clot

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3
Q

where are procoagulants found in a vessel wall

A

Below the initial single cell endothelial layer

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4
Q

What is the primary initiator of the coagulation cascade

A

Tissue factor

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5
Q

Where is tissue factor found

A

On some of the vascular smooth muscle cells below the endothelial layer of a vessel wall

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6
Q

Vessel constriction is more important in X blood vessels

A

small

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7
Q

Platelets are derived from X which are the largest cells in the bone marrow.

A

megakaryocytes

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8
Q

megakaryocytes are X hence the large nucleus.

A

polyploidy

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9
Q

There is a small source of megakaryocytes from the X.

A

lungs

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10
Q

How do megakaryocytic physically become platelets

A

Platelets bleb off the megakaryocyte off finger-like structures.

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11
Q

What granules are within platelets and what do they contain (2, 4 and 2)

A

α-granule (GF’s, fibrinogen, FV and VWF), dense granules (ADP and ATP help augment functions of surrounding platelets when secreted)

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12
Q

what helps the platelet adopt its shape when active.

A

The actomyosin and microtubules

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13
Q

4 roles of platelets?

A

Haemostasis and thrombosis, cancer
atherosclerosis
infection
inflammation

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14
Q

How does VWF help with platelet activation

A

VWF circulates
Vascular injury exposes subendothelial matrix containing collagen, which binds VWF via its exposed collagen binding sites.
This causes VWF to transition from folded globular form to extended linear polypeptide form by the shear forces of blood
This reveals platelet binding sites
The platelets are recruited and bind to VWF through Gp1b.

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15
Q

What activates VWF

A

Collegen exposure

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16
Q

When and where and through what receptors do platelets bind to collagen

A

using Gp6 and α2β2 but this can only happen in low shear conditions (in veins)

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17
Q

What 3 things can activate a platelet

A

Collagen
VWF
Thrombin

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18
Q

What happens when a platelet is activated

A

When activated the platelet releases its granules, changes their shape and change the composition of their phospholipid surface.
In the granules are ADP and thromboxane that are released in a cloud and prime more platelets that travel near that cloud causing them to aggregate.

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19
Q

How do platelets aggregate (receptor and molecule)

A

Intergrin α2bβ3 binds fibrinogen and cross links platelets together and causes them to aggregate

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20
Q

Platelet count normal is between XXXXX x10^9/litre.

A

150-400

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21
Q

What platelet count leads to spontaneous bleeding

A

less than 40

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22
Q

What platelet count can lead to purpura

A

below 10

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23
Q

what is the key role of thrombin

A

to cleave fibrinogen to leave sticky fibrin

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24
Q

where are the majority of clotting factors produced

A

Liver

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25
Q

All zymogen are X proteases

A

serine

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26
Q

once activated, serine proteases cleave substrates after X and Y residues

A

specific Arg and Lys

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27
Q

What factor usually kicks off the clotting

A

Tissue factor

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28
Q

Tissue factor activates …

A

factor 7 to 7a

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29
Q

Why and where is TF expression higher

A

Lungs, brain, heart etc to provide further haemostat protection to these organs

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30
Q

What is the only procoagulant factor in the clotting cascade that require to proteolytic activation

A

Tissue factor

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31
Q

4 domains of TF?

A

G1a domain, 2 EGF like domains and serine protease domain

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32
Q

What domains do FVII, FIX, FX and PC share

A

4 domains
G1a domain
2 x EGF domain
serine protease domain

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33
Q

Which factors have 4 homologous domains
(G1a domain
2 x EGF domain
serine protease domain)

A

FVII, FIX, FX and PC

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34
Q

What does the GIa domain bind to

A

negatively charged phospholipid surfaces on platelets

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35
Q

GIa domains is dependent on vitamin X for their development

A

K

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36
Q

GIa domains have XX residues

A

Carboxyglutamic acid

37
Q

What binds to what to cause the GIa domain to fold up into its phospholipid binding form

A

Ca2+ ions binding to the carboxyglutamic domain

38
Q

what does warfarin do and how does it work

A

Warfarin – anticoagulant – is a vitamin k antagonist and causes dysfunctional Gla domain formation.

39
Q

Which domains of FVII interact with TF

A

all domains

40
Q

Which domains of FVII interact with TF phospholipid cell surfaces

A

GIa

41
Q

What activates FVII

A

Tissue factor

42
Q

Factor VIIa activates …

A

Factors X and IX

43
Q

What activates factor X

A

FVIIa

44
Q

What activates factor IX

A

FVIIa

45
Q

Factor Xa activates …

A

Prothrombin to thrombin, but if its by itself it is insufficient and only small quantities of thrombin are generated

46
Q

Factor IXa activates …

A

FX with FVIIIa

47
Q

Factor VIIIa’s purpose …

A

Cofactor that enhances the activation of FXa with FIX

48
Q

Factor Va’s purpose …

A

cofactor that catalyses an increased activation of thrombin from prothrombin by FXa

49
Q

What activates factor VIII

A

Thrombin

50
Q

What activates factor V

A

Thrombin

51
Q

Factor XIa activates …

A

FIX via the intrinsic pathway

52
Q

What activates factor XI

A

Intrinsic pathway

53
Q

What activates prothrombin,

A

FVa

54
Q

Thrombin activates …

A

fibrinogen to fibrin, as well as FV and FVIII

55
Q

What are the cofactors that enhance the response of their corresponding factors

A

FVIII enhances FIX to convert FX to FXa

FVa enhances FXa’s confession to prothrombin to thrombin

56
Q

What causes haemophilia a

A

FVIII deficiency

57
Q

FVIII deficiency is known as

A

haemophilia a

58
Q

What causes haemophilia b

A

FIX deficiency

59
Q

FIX deficiency is known as

A

haemophilia b

60
Q

what type of genetic disease is haemophilia a and b

A

X linked

61
Q

where does antithrombin act

A

FXa, FIXa, FXIa and at thrombin

62
Q

Where does activated protein C and protein S act

A

FVa and FVIIIa

63
Q

Where does tissue factor pathway inhibitor act

A

FVIIa and FXa

64
Q

FXa is inactivated by…

A

antithrombin and TFPI

65
Q

FIXa is inactivated by…

A

antithrombin

66
Q

FVa is inactivated by…

A

activated protein C and protein S

67
Q

FVIIIa is inactivated by…

A

activated protein C and protein S

68
Q

FVIIa is inactivated by…

A

TFPI

69
Q

Thrombin is inactivated by…

A

antithrombin

70
Q

Thrombin is inactivated by…

A

antithrombin

71
Q

Protein C is activated by

A

Thrombin-thrombomodulin complex on endothelial cells

72
Q

What is thrombin also known as

A

FIIa

73
Q

What is FIIa aka

A

thrombin

74
Q

How does FIIa/thrombin activate protein C

A

thrombin binds to thrombomodulin and becomes anticoagulant and unable to cleave fibrinogen. this complex then cleaves activation peptide from Protein C

75
Q

Main purpose of the protein C anticoagulant mechanism

A

Prevents coagulation spreading too far

76
Q

Protein C pathway regulates the propagation phase of coagulation by XX thrombin generation - it does not Y thrombin

A

downregulating

inhibit

77
Q

Antithrombins job?

A

inactivates FXa, thrombin, FXa and FXIa

AT mops up free serine proteases that escape the site of vessel damage and stops coagulation happening elsewhere

78
Q

3 endogenous anticoagulant mechanisms?

A

TFPI
Protein C and protein S
Antithrombin

79
Q

What does heparin do and how does it achieve this

A

Anticoagulant that makes antithrombin more effective by speeding up its reaction

80
Q

What activates plasminogen

A

tissue plasminogen activator

81
Q

What does plasmin do

A

degrades fibrin products

82
Q

3 anticoagulant drugs?

A

heparin, warfarin and direct acting anticoagulants

83
Q

anti platelet agents?

A

aspirin and P2Y12 blovkers

84
Q

4 tests to check integrity of the coagulation system?

A

prothrombin time

activated partial thromboplastin time

platelet function tests
d-dimer tests

85
Q

What endogenous molecule can be used therapeutically for thrombolysis

A

tPa

86
Q

disseminated intravascular coagulation shows elevated …

A

fibrin degradation products

87
Q

Aspirin targets what enzyme and inhibits the formation of what from what

A

cyclooxygenase inhibiting formation of TXA2 from AA

88
Q

Which receptors of platelets bind to collagen

A

Glp1a

89
Q

Which receptors of platelets bind to VWF

A

Glp1b

Haematology Y2 (11 decks)

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