S1: Haemostasis Flashcards

1
Q

Why does our blood clot?

A
  • keep blood in

- keep pathogens out

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2
Q

What is haemostasis?

A

It is a physiological process that stops bleeding at the site of an injury while maintaining normal blood blow elsewhere in the circulation

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3
Q

How is blood loss stopped?

A

Formation of plug compose of platelets and fibrin - clotting is localised

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4
Q

What happens when collagen is exposed to the blood?

A

Endothelium in blood vessels normally maintains an anticoagulant surface to maintain blood in its fluid state.
However, when collagen (under endothelium) comes into contact with blood components, clotting is activated.

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5
Q

What are the 3 inter-related processes that influence one another?

A
  • Blood clotting
  • Inflammation
  • Wound healing
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6
Q

What are the two main processes of haemostasis?

A

Primary Haemostais
Secondary Haemostasis

Primary and secondary steps are intertwined at many points and are not really separate processes.

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7
Q

What is primary haemostasis?

A

Platelet aggregation and platelet plug formation

Platelets:

  1. Adhere
  2. Activate
  3. Aggregate (via fibrinogen and fibrin receptors)
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8
Q

What is secondary haemostasis?

A

Deposition, of insoluble fibrin generated by the coagulation cascade

Thrombin (protease):

  1. Cleaves circulating soluble fibrinogen
  2. Into insoluble fibrin mesh
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9
Q

What is the coagulation cascade?

A

Reactions which convert fibrinogen (a soluble protein) into insoluble strands of fibrin which together with platelets form a stable thrombus.

  • utilises thrombin (protease)
  • fibrinogen is the pre-cursor to fibrin
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10
Q

What are the two models of clotting pathways?

A

1) Old school cascade model

2) Cell based model

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11
Q

What is the mechanism of platelet adherence?

A
  1. Endothelium continuously releases small amounts of von WIllebrand factor which circulates in the blood.
  2. Collagen becomes exposed to blood (because endothelium is damaged) and von Willebrand factor binds to it.
  3. Platelets express receptors for both collagen and von Willebrand factor and becomes active when these proteins to them
  4. Activated platelets express functional fibrinogen receptors which are required for aggregation
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12
Q

What is von Willebrand factor?

A

Von Willebrand is a blood glycoprotein that binds to other proteins, in particular factorVIII, and it is important in platelet adhesion to wound sites.
- It is released by the endothelium

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13
Q

Where is von Willebrand stored?

A

Endothelial cells also store von willebrand factor in weibel-palade bodies for release when appropriately stimulated

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14
Q

What is the mechanism of platelet activation?

A
  1. Once activated, platelets begin to aggregate by binding fibrinogen which links them together
  2. At the same time, platelets release multiple pro activation/aggregation signalling molecules that activate other platelets.
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15
Q

Give some examples of pro activation/aggregation signalling molecules

A

Adenosine diphosphate (ADP

Thromboxane A2 (TXA2)

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16
Q

What is the mechanism of platelet aggregation?

A

Platelets are activated by other platelets. They bind to the other platelets by linking fibrinogen aggregating them together. This is called amplification which increases the number of platelets.

17
Q

What is the sub endothelial trigger for the coagulation cascade?

A

Tissue factor

18
Q

What is the mechanism for the production of thrombin using tissue factor?

A
  1. Tissue factor (TF) is expressed nearly all sub-endothelial cells and it activates the coagulation cascade to initiate minor bursts of haemostasis
  2. Factor VIIa binds to tissue factor which activates FXa and leads to the convertion of prothrombin to thrombin
  3. Thrombin activated receptors on platelets as well as the endothelium, amplifying platelet aggregation and initiating release release of stored von Willebrand factor from weibel-palade body in endothelial cells.
19
Q

What converts prothrombin to thrombin?

A

FXa

20
Q

What activates Factor Xa (Prothrominase complex)?

A

Factor FVIIa binding to Tissue Factor

21
Q

What is the mechanism of the amplification stage of the coagulation cascade?

A
  1. Thrombin activates 2 cofactors: Factor VIIIa and Factor Va.
  2. These form calcium ion dependent complexes on the surface of platelets with factor Xa and factor IXa
  3. Factor Xa and Factor IXa accelerate the production of factor Xa and consequently thrombin. This is the amplification stage of the coagulation cascade.
22
Q

What is factor IXa also called?

A

Tenase complex

23
Q

What two complexes amplify the production of FXa (and consequently thrombin)?

A

Tenase complex - FIXa

Prothrominase complex - FXa

24
Q

What two complexes does thrombin activate?

A

Factor VIIIA

Factor Va

25
Q

Why is thrombin made during secondary haemostasis?

A

It cleaves circulating soluble fibrinogen into an insoluble fibrin mesh

26
Q

What activates plasmin from plasminogen?

A

t-PA = Tissue Plasminogen Activator

27
Q

What does plasmin do?

A

It breaks down fibrin

28
Q

What is tPa used for clinically?

A

Stroke

Decrease in t-PA, means decrease in plasmin and increase in fibrin

29
Q

What is haemophilia?

A

The blood failing to clot.

This can occur through mutations in coagulation factors

30
Q

What is thrombosis?

A

Clotting int he wrong place e.g. stroke, venous DVT

31
Q

What does depletion of clotting factors and platelets lead to?

A

Bleeding

32
Q

Why is coagulation activated during sepsis?

A
  • Coagulation activation can be beneficial during infections
  • Coagulation proteins are necessary for the eradication of invading proteins
  • Tissue factor also triggers coagulation independent signalling pathways mediated by protease activated receptors (PARs) on immune cells
  • PAR dependent signals evoke pro and anti inflammatory pathways that regulate migration and proliferation of immune cells
  • ‘Containment hypothesis’
33
Q

What is ‘containment hypothesis’?

A

Coagulation activation contributes to pathogen clearance by forming a physical barrier facilitating pathogen clearance by immune cells