Haemostasis Flashcards

1
Q

What is haemostasis?

A

Process involving stoppage of blood through blood vessels following trauma

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2
Q

What is primary haemostasis?

A

Formation of unstable platelet plug at the site of damaged vessel wall

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3
Q

What is secondary haemostasis?

A

Coagulation, formation of stable fibrin clot

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4
Q

What is coagulation?

A

Stimulation of blood clotting process whereby blood transitions from a liquid to semi-solid state, forming a coherent mass

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5
Q

What is thrombosis?

A

Limit the extent of the response to the area to injury to prevent excessive or generalised blood clotting
Thrombosis is localised coagulation

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6
Q

What is fibrinolysis?

A

Initiating the process to enzymatically breakdown the fibrin in blood clots.

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7
Q

What is the structure of platelets?

A

Non-nucleated discoid granule containing cells

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8
Q

What cells do platelets derive from?

A

Megakaryocytic cytoplasmic fragmentation

Myeloid progenitor cells, formed in the bone marrow

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9
Q

What glycoprotein receptor do platelets directly bind onto within the collagen exposed damaged endothelium?

A

Glycoprotein-1a receptor

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10
Q

What receptor do platelets indirectly bind onto?

A

Von willebrand factor

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11
Q

What does Von Willebrand factor bind with?

A

Glycoprotein-1b

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12
Q

What results from platelet adhesion?

A

Structural changes from sacs to rounded discs with interlacing projections

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13
Q

What term describes the interlocking projections on platelets?

A

Spicules and filopodia

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14
Q

What is the function of spicules and filopodia?

A

Encourages platelet-platelet interaction

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15
Q

What proceeds platelet adhesion?

A

Initiates activation and release of clotting factors from storage granules (alpha dense granules), membrane invaginated to form canalicular system through which granules secrete contents, ADP

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16
Q

What platelet system is formed upon platelet adhesion and activation?

A

Canalicular system

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17
Q

What storage granules release clotting factors?

A

Alpha and dense granules

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18
Q

What is also released upon platelet activation?

A

ADP

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19
Q

What is produced during platelet activation?

A

Thromboxane A2 (prostaglandin)

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20
Q

What is thromboxane A2?

A

Prostaglandin

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21
Q

What is thromboxane A2 synthesised from?

A

Arachidonic acid

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22
Q

What is the function of thromboxane A2?

A

Stimulates platelet aggregation, and the activation of new platelets (positive feedback lipids mediator)
Vasoconstrictor

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23
Q

How does thromboxane A2 cause platelet aggregation?

A

Binds to thromboxane a2 receptor, finalised by conformational change (ADP induced) in GP2B; gp3A to provide binding sites for fibrinogen.

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24
Q

Which glycoproteins undergo conformational change due to thromboxane A2?

A

GP2B

GP3A

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25
Q

What is fibrinogen?

A

Soluble blood protein, essential for linking platelets together to form untstable platelet plug

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26
Q

What is prostacyclin?

A

Potent vasodilator, suppresses platelet activation, and prevents inappropriate platelet aggregation. Stabilises clot

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27
Q

What is the mechanism of action of aspirin?

A

Aspirin inhibits the production of thromboxane A2 by irreversibly blocking the action of cycle-oxygenase (COX); thereby reducing platelet aggregation

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28
Q

How long does a single dose of aspirin persist?

A

7 days,

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29
Q

What is the mechanism of Acton of clopidrogel?

A

Irreversibly blocks the ADP receptor P2Y12 on platelet cell membrane; thus ADP induced conformation change cannot occur

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30
Q

What is von Willbrand factor?

A

Multimeric glycoprotein synthesised by endothelial cells and megakaryocytic, mediates the adhesion of platelets binding onto glycoprotein-1b receptor.

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31
Q

What is secondary haemostasis?

A

Secondary haemostasis is responsible for the formation of a stable clot through coagulation mechanisms. The primary platelet plug is insufficient for larger vessel injury (structurally weak)- Fibrin formation stabilises the platelet plug, adding integrity.

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32
Q

What is the function of thrombin?

A

Proteolytic enzyme cleaves fibrinogen to an insoluble protein, fibrin; forms fibrin mesh fibre

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33
Q

Where are the majority of clotting factors synthesised in?

A

Liver

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34
Q

Whereis factor V synthesised?

A

megakaryocytes

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35
Q

Where is VWF made?

A

Megakaryocytes + endothelial cells

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36
Q

Which clotting factors are dependent on vitamin K?

A

Factors II (Prothrombin)
VII (7)
IX (9)
X (10)

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37
Q

Why is vitamin K essential for the four clotting factors?

A

For their glutamic acid resides to be carboxylated into activation

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38
Q

What is the term for inactive enzyme (proenzyme)?

A

Zymogen

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39
Q

How are proenzymes activated?

A

Splitting of peptide bonds.

40
Q

What are cofactors?

A

V and VIII (5 & 8)

41
Q

What is the function of calcium ion in the clotting cascade?

A

Essential for binding of activated clotting factors to the phospholipid surfaces of platelets

42
Q

What triggers the coagulation cascade?

A

Tissue factor

43
Q

Which cells present tissue factor?

A

Endothelial cells, leukocytes

Exposed at site of injury

44
Q

Which factor does TF bind to?

A

VIIa activaes factors IX –> IXA

X –> Xa

45
Q

What does Xa and IXa lead to?

A

Activation of prothrombin (ii) to thrombin (IIa) (Small initial amount)

46
Q

What mediates activation of co-factors V, 8 XI, and platelets?

A

Thrombin

47
Q

What does factor XI do?

A

Mediates IX –> IXa, concerted with 8a, amplifies X to Xa

Rapid burst of thrombin generated, converted fibrinogen to fibrin

48
Q

What is the mechanism of action of warfarin and direct oral anticoagulants?

A

Potentiates antithrombin leading to the inactivation of Xa and IIa (Thrombin)

49
Q

How is Heparin administered?

A

Intravenously or by subcutaneous injection

50
Q

What is the mechanism of a action of Warfarin?

A

Vitamin K antagonist, interferes with the carboxylation of glutamic acid residues
Thus interrupting II,VII, IX and X

51
Q

How is warfarin prescribed?

A

Orally

52
Q

What is the purpose of natural anticoagulation pathways?

A

Confined to site of injury and prevents spontaneous activation

53
Q

Which proteins are important in regulating the coagulation system?

A

Antithrombin
Protein c
Protein S

54
Q

What activates Protein C?

A

Thrombin binds to thrombomodulin on the endothelial cell surface
Activated protein c, inactivates Va, and VIIIa in the presence of co factor protein S

55
Q

What is the function of protein S?

A

Behaves as a cofactor

56
Q

How are thrombin and factor Xa inactivated?

A

Antithrombin

57
Q

How is antithrombin action potentiated?

A

By heparin

58
Q

What is fibrinolysis?

A

Fibrinolysis proceeds after haemostasis to cleave and lyse fibrin clots.

59
Q

Which enzyme is involved in fibrinolysis?

A

Plasmin

60
Q

What is the inactive form of plasmin?

A

Plasminogen

61
Q

How is plasminogen activated into plasmin?

A

Tissue plasminogen-activator (t-PA), following binding to the lysine residues of fibrin

62
Q

What is formed from the degradation of fibrin?

A

Fibrin degradation products

63
Q

What are the clinical applications of recombinant t-pa?

A

Increased plasmin activation, thereby this stimulates elevated levels of fibrinolysis; lysising thrombosis

64
Q

What are the risks with thrombolytic therapy?

A

High risk of associated bleeding

65
Q

What is an example of an antifibronlytic drug?

A

Tranexamic acid, synthetic derivative of lysine

66
Q

How does Tranexamic acid work?

A

Plasminogen binding, behaves as a competitive inhibitor; prevents lysine from binding to lysine residues in fibrin
Cannot be activated into plasmin, fibrin is therefore not lysed

67
Q

What disorder will tranexamic acid be used for?

A

Haemophillia

68
Q

What are the three phases of coagulation?

A

Initiation, amplification and propagation.

69
Q

What clotting factors are intrinsic?

A

9, 10, 11, 12

8 and 5

70
Q

Which clotting factors are extrinsic?

A

Tissue factor

7, 10, 5

71
Q

Name the two types of coagulation tests:

A
Prothrombin time (PT)
Activated partial thromboplastin time (APTT)
72
Q

Which pathway measures the integrity of the extrinsic?

A

Prothrombin time

73
Q

How is blood collected for prothrombin time?

A

Collected with sodium citrate,chelates calcium, prevents blood clotting in bottle, spun to produce platelet poor plasma

74
Q

What is added to prothrombin time blood?

A

TF & recombinant thromboplastin added to citrated plasma; added with calcium to start reaction

75
Q

What does prothrombin time measure?

A

The time it takes for the mixture to clot upon calcium addition

76
Q

Why my prothrombin time be prolonged?

A

Due to the reduction in the activity of , 7, 10, 5, 2 or fibrinogen (prothrombin is a misnomer)

77
Q

How is warfarin measured?

A

INR ratio, prothrombin time used to measure vitamin K antagonist therapy

78
Q

Which pathway does APTT measure?

A

The intrinsic pathway

79
Q

Which factor is activated by a contact activator?

A

XII (12)

80
Q

What are the examples of a contact activator?

A

Silica or kaolin

81
Q

How is APTT measured?

A

Contact activator, with phospholipid added to the citrated plasma, sample followed by calcium, time taken to clot is measured

82
Q

What does prolongation of the APTT mean?

A

Reduction in single or multiple clotting factors

83
Q

What is haemophilia A?

A

Factor VIII deficiency

84
Q

What is haemophilia B?

A

Factor 9 deficiency

85
Q

What may cause bleeding?

A

Reduction in platelet number or function
Failure of platelet production caused by bone marrow infiltration, megaloblastic anaemia, drugs, viruses, B12 and folate deficiency
Hereditary thrombocytopenia

86
Q

What is disseminated intravascular coagulation?

A

Formation of miniature clots throughout the blood stream depletes platelet resources

87
Q

What are blood abnormalities divided into?

A

Congenital and acquired

88
Q

What are the congenital causes of haemophilia?

A

Reduction in VWF, and inherited bleeding disorder

89
Q

What can be used as treatment for haemophilia?

A

Recombinant factor concentrates

90
Q

What are some examples of acquired causes of reduced coagulation factors?

A

Disseminated intravascular coagulation
Clotting factors and plasma fibrinogen depleted- impairs haemostatic activity, excessive bleeding, high FDPs
Causes: Bacterial sepsis, advanced cancer, obstetric emergencies
Liver disease

91
Q

What is thrombosis?

A

Condition in which blood transforms from a liquid to a solid state within the cardiovascular system- produces mass of coagulated blood (thrombus) within an intact vessel. Thrombosis in an artery obstructs the blood flow to the tissue it supplies.

92
Q

What is an embolism?

A

Carried blood clot that becomes lodged within the circulatory system

93
Q

What is Virchow’s triad?

A

Blood
Blood flow
Vessel wall

94
Q

What is dominant in vessel walls?

A

Arteriole thrombosis

95
Q

What is dominant in blood flow?

A

Both arterial and venous thrombosis

96
Q

What is venous thrombosis dominant in?

A

Blood

97
Q

What leads to thrombosis?

A

Reduced levels of anticoagulant proteins (antithrombin deficiency) thrombopenia
Reduced fibrinolytic actibity
Increased levels of clotting factors
Factor VIII increases during pregnancy