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Block 2 CTB > Haemostasis and the coagulation cascade > Flashcards

Haemostasis and the coagulation cascade Flashcards

1
Q

Define haemostasis.

A

A precisely orchestrated series of regulatory processes that culminate in the formation of a blood clot that limits bleeding from an injured vessel

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2
Q

What 3 key things does haemostasis allow for?

A

Blood to be in a fluid state in normal vessels

Formation of a localised haemostatic clot at sites of vascular injury

Prevents haemorrhage

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3
Q

Define coagulation.

A

Formation of a haemostatic plug (clot)

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4
Q

Define fibrinolysis.

A

Breakdown of fibrin within a haemostatic plug (clot)

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5
Q

Define haemorrhage.

A

Extravasation of blood into the extravascular space

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6
Q

Define thrombosis.

A

Formation of a solid mass of blood products in a vessel lumen

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7
Q

What are the 3 main components of haemostasis?

A

Vascular wall (endothelium and subendothelial structures)

Platelets

Coagulation cascade

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8
Q

Describe normal endothelium in terms of platelets, coagulation, and fibrinolysis.

A

Antiplatelet
Anticoagulant
Fibrinolytic

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9
Q

What 2 substances do endothelial cells release which prevents platelet aggregation?

A

Prostacyclin

Nitric oxide

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10
Q

What 2 substances do endothelial cells release which prevents coagulation?

A

Heparan sulfate

Thrombomodulin

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11
Q

Which substance do endothelial cells produce which helps dissolve clots? How does it work?

A

Tissue plasminogen activator (tPA)

It converts plasminogen to plasmin. Plasmin breaks down fibrin in clots

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12
Q

What are the 2 main roles of platelets in coagulation?

A

Form the primary haemostatic plug

Provide a surface for the recruitment and concentration of coagulation factors and acts as a catalytic membrane

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13
Q

What are the 4 steps of haemostasis?

A

Vasoconstriction

Primary haemostasis

Secondary haemostasis

Clot stabilisation and resorption

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14
Q

In the vasoconstriction step of haemostasis, the release of what substance causes vasoconstriction?

A

Endothelin

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15
Q

What are the 2 aims of the initial step of vasoconstriction in haemostasis?

A

Minimise blood loss

Maximises interactions between platelets, clotting factors, and vessel wall

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16
Q

What are the 3 stages of primary haemostasis (formation of the primary platelet plug)?

A

Platelet adhesion
Platelet activation
Platelet aggregation

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17
Q

Describe how platelets adhere to the exposed subendothelial collagen at a site of injury.

A

They first bind via von Willebrand factor (vWF) and then bind directly to the collagen

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18
Q

Describe how platelets change during platelet activation and which 3 substances they release.

A

Platelets change shape to become more spiky. They release substances such as ADP, serotonin, thromboxane A2

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19
Q

In platelet aggregation, how do platelets link together?

A

Fibrinogen acts as a bridge between GPIIb/IIIa receptors on adjacent platelets, linking them together

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20
Q

Secondary haemostasis is otherwise known as what?

A

Coagulation cascade

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21
Q

Describe how fibrin is generated in secondary haemostasis.

A

Tissue factor (TF) is expressed on subendothelial cells and is exposed when a blood vessel is damaged. Tissue factor binds to and activates Factor VII. Thrombin is generated and cleaves fibrinogen into fibrin

22
Q

Factor II is otherwise known as what?

A

Prothrombin

23
Q

What are the 6 coagulation factors?

A

Factors II, VII, IX, X, XI, XII

24
Q

What are the 2 coagulation cofactors?

A

Factors V and VIII

25
Q

What are the 5 coagulation cascade requirements?

A

Coagulation factors (pro-enzymes) and activated coagulation factors (enzymes)

Cofactors (reaction accelerators)

Negatively charged phospholipid surface (activated platelets)

Calcium ions

Vitamin K

26
Q

The extrinsic coagulation pathway is measured clinically as what?

A

Prothrombin time

27
Q

What is the extrinsic coagulation pathway initiated by?

A

Tissue factor

28
Q

The intrinsic coagulation pathway is measured clinically as what?

A

Activated partial thromboplastin time (aPTT)

29
Q

What is the intrinsic coagulation pathway initiated by?

A

When FXII comes into contact with a negatively charged surface, activating it to become FXIIa

30
Q

Which 2 complexes can Factor X in the common pathway be activated by in each pathway?

A

TF-FVIIa-Ca2+ complex (extrinsic pathway)

Tenase complex (intrinsic pathway)

31
Q

What comprises the tenase complex?

A

FIXa-FVIIIa-Ca2+

32
Q

What comprises the prothrombinase complex?

A

FXa-FVa-Ca2+

33
Q

What is the action of FXIII?

A

Covalently cross-linking fibrin polymers, stabilising the secondary haemostatic plug

34
Q

Which substance is a circulating inhibitor of coagulation?

A

Antithrombin III

35
Q

Describe the 3 anticoagulant effects of the adjacent intact endothelium.

A

Tissue factor pathway inhibitor – inhibits TF-FVIIa-Ca2+ complexes

Thrombomodulin and endothelial protein C receptor – activates protein C – protein C/ protein S complex inhibits factors Va and VIIIa

Heparin-like molecules – binds and activates antithrombin III

36
Q

What causes the fibrinolytic effect of the adjacent intact endothelium?

A

Tissue plasminogen activator (t-PA)

37
Q

How does heparin reduce coagulation?

A

It binds reversibly to antithrombin II and enhances its inactivation of thrombin and FXa. It induces a conformational change that “opens up” antithrombin III

38
Q

What is the key effect of low dose heparin?

A

Inhibits thrombosis

39
Q

What is the key effect of high dose heparin?

A

Prevents progression of existing clots

40
Q

What are the 2 types of heparin?

A

Unfractionated heparin

Low molecular weight heparin (LMWH)

41
Q

What does unfractionated heparin inactivate?

A

FXa and thrombin

42
Q

What does low molecular weight heparin inactivate?

A

4FXa

43
Q

Which type of heparin is preferred for use as treatment and what is the exception to this?

A

Low molecular weight heparin is preferred, except in patients with severe renal failure

44
Q

What is the molecular structure of fondaparinux?

A

Synthetic pentasaccharide

45
Q

What is the MOA of fondaparinux?

A

Binds irreversibly to antithrombin III. Enhances antithrombin III’s ability to inhibit factor Xa, but does not inactivate thrombin

46
Q

List 2 uses of fondaparinux.

A

VTE prophylaxis for surgical patients

Treatment of unstable angina and NSTEMI

47
Q

What are the 2 ways plasminogen is converted to plasmin?

A

FXII-dependent pathway

Tissue plasminogen activator (t-PA)

48
Q

What is the degradation product of fibrin?

A

D-Dimer

49
Q

Name an inherited defective haemostasis disorder.

A

Haemophilia A (factor VIII deficiency)

50
Q

Name an acquired defective haemostasis disorder.

A

Disseminated intravascular coagulation (DIC)

Block 2 CTB (17 decks)

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