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Principles Of Medicine > Haemostasis > Flashcards

Haemostasis Flashcards

1
Q

3 reasons why haemostasis is important?

A
  1. Allow the stimulation of blood clotting processes following injury, in which blood changes from its liquid state (coagulation)
  2. Limit the extent of the response to the area of injury to prevent excessive or generalised blood clotting (thrombosis)
  3. Start the process that eventually leads to the breakdown of the clot as part of the process of healing (fibrinolysis)
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2
Q

What are the 3 processes that halt blood flow?

A
  1. Contraction of blood vessels (vasoconstriction)
  2. Formation of an unstable platelet plug at the site of the vessel wall damage (primary haemostasis)
  3. Formation of a stable fibrin clot (secondary haemostasis/coagulation)
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3
Q

What are platelets?

A

Platelets are discoid, non-nucleated, granule-containing cells that are derived from myeloid stem cells. Platelets are formed in the bone marrow by the fragmentation of megakaryocyte cytoplasm and have a circulating lifespan of around 10 days.

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4
Q

How to platelets stick to damaged endothelium?

A

The plasma membrane contains glycoproteins (GPs) that are important for the platelet’s interactions. Following injury to the vessel wall platelets stick to the damaged endothelium, either directly to collagen via the platelet GPIa receptor or indirectly via von Willebrand factor (VWF), which binds to the platelet GPIb receptor. This adhesion of platelets causes them to become activated and changes their shape from a disc to a more rounded form with spicules to encourage platelet-platelet interaction.

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5
Q

What are the 2 main types of granules released by platelets after adhesion?

A

Alpha and dense granules which contain ADP (dense), fibrinogen and von Willebrand factor (alpha)

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6
Q

What important vasoconstrictor can platelets produce?

A

Thromboxane A2 from arachidonic acid.

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7
Q

What is the effect of the generation of thromboxane A2 and release of ADP?

A

Leads to positive feedback loop stimulating further platelet recruitment and aggregation.

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8
Q

What receptor does ADP bind to?

A

P2Y12

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9
Q

What happens to the GPIIb/IIa receptor after platelet activation?

A

Change in conformation exposing fibrinogen binding sites.

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10
Q

Function of fibrinogen

A

Further activates platelets through outside in signalling and links platelets together to form the platelet plug.

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11
Q

How is platelet aggregation naturally counterbalanced?

A
  1. Active flow of blood

2. Release of prostacyclin from endothelial cell

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12
Q

Function of prostayclin

A

Vasodilator and suppresses platelet activation

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13
Q

Mechanism of aspirin?

A

Aspirin inhibits the production of thromboxane A2 by irreversibly blocking the action of cyclo-oxygenase (COX), resulting in a reduction in platelet aggregation.

COX is also used for prostacyclin production however endothelial cells can synthesise more COX whereas the non-nuclear platelets cannot.

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14
Q

Mechanism of clopidogrel?

A

Clopidogrel works by irreversibly blocking the ADP receptor (P2Y12) on the platelet cell membrane.

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15
Q

Where are clotting factors except 8 and VWF synthesised?

A

Liver

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16
Q

Where are factors 8 and VWF formed?

A

Endothelial cells. VWF is also incorporated into platelet granules.

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17
Q

Some factors are dependent on a specific vitamin for their synthesis.
What is the name of the factors and the vitamin and why is the vitamin required?

A

Factors 2, 7, 9, 10
Dependent on vitamin K
Vitamin K is required for carboxylation of their glutamic acid residues.

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18
Q

What is the inactive form of a clotting factor called?

A

Zymogen (proenzyme)

19
Q

Which factors are cofactors?

A

5 and 8

20
Q

What is the target side of these clotting factors?

A

Exposed phospholipid surface of platelets

21
Q

What is the role of calcium ions?

A

Calcium ions play an important role in the binding of activated clotting factors to the phospholipid surfaces of platelets.

22
Q

Outline the extrinsic pathway (TSNT)

A 
T = tissue factor
S = seven
N = nine
T = 10
  1. Tissue factor binds to 7.
  2. Activation of 7 leads to activation of 10 with 5a cofactor.
  3. This leads to conversion of prothrombin (2) to thrombin (2a)
  4. This then leads to the activation of 12.
23
Q

Outline the intrinsic pathway beginning from the activation of 12 (TENET)

A 
T = 12
E = 11
N = 9
E = 8
T = 10
  1. 12 activates 11
  2. 11 activates 9 with 8a cofactor
  3. 9 activates 10 with 5a cofactor
  4. This leads to a much larger more rapid generation of thrombin.
  5. Thrombin coverts soluble fibrinogen into the solid fibrin forming the fibrin mesh.
24
Q

What are the 3 phases of coagulation cacade?

A

Initiation, amplification, propgation

25
Q

2 methods of natural anticoagulation?

A
  1. Thrombin binds to thrombomodulin on the endothelial cell surface leading to activation of protein C to activated protein C (APC). APC inactivates factors 5a and 8a in the presence of a co-factor protein S.
  2. Thrombin and factor 10a are inactivated by the circulating inhibitor antithrombin. The action of antithrombin is markedly potentiated by heparin: this occurs physiologically by the binding of antithrombin to endothelial cell-associated heparins.
26
Q

What are the 3 main anticoagulant drugs?

A

Warfarin, heparin, DOACs

27
Q

Mechanism of heparin

A

Heparin works indirectly by potentiating the action of antithrombin leading to the inactivation of factors 10a and thrombin.

Heparin is administered intravenously or by subcutaneous injection.

28
Q

Mechanism of warfarin

A

A vitamin K antagonist that works by interfering with protein carboxylation thus reducing the synthesis of functional 2, 7, 9 and 10.

Because it reduces the synthesis rather that inhibiting existing factors it takes several days to take effect.

29
Q

Outline the natural fibrinolytic system

A

Plasminogen activated by t-PA to plasmin after both plasminogen and t-PA bind to lysine residues on fibrin.

It is inhibited by circulating antiplasmin

30
Q

Mechanism of tranexamic acid?

A

A synthetic derivative of lysine that works by binding to the lysine binding site on plasmiogen preventing them from binding to lysine residues on fibrin (competitive inhibition). This prevents the activation of plasminogen to plasmin.

31
Q

Outline PT test

A

​Blood is collected into a bottle containing sodium citrate (usually blue-topped as in the picture), which chelates calcium thus preventing the blood from clotting in the bottle

The sample is spun to produce platelet-poor plasma

A source of TF and phospholipid is added to the citrated plasma sample, together with calcium to start the reaction; the length of time taken for the mixture to clot is recorded.

32
Q

Why might PT be prolonged?

A

If there is a reduction in the activity of factors VII, X, V, II (prothrombin) or fibrinogen

33
Q

Outline APTT test

A

Performed by the contact activation of factor XII by a surface such as glass, or using a contact activator such as silica or kaolin.

Contact activator, together with phospholipid, is added to the citrated plasma sample followed by calcium; the time taken for this mixture to clot is measured

34
Q

Why might APTT be prolonged?

A

An isolated prolonged APTT (i.e. normal PT) is seen in patients with haemophilia A (factor VIII deficiency), haemophilia B (factor IX deficiency) and factor XI deficiency. However this may also be caused by factor XII deficiency which does not result in bleeding.

35
Q

Causes of increased bleeding? (3)

A
  1. Reduction in platelet number or function (primary haemostasis –platelet plug)
  2. Reduction in coagulation factor(s) (secondary haemostasis – fibrin clot)
  3. Increased fibrinolysis
36
Q

Why might platelet number fall? (3)

A
  1. Failure of platelet production
  2. Shortened platelet survival
  3. Increased splenic pooling
37
Q

Why might platelet function fall?

A

Antiplatelet drugs or inherited causes

38
Q

What is von Willebrand disease?

A

Reductions in the level or function of VWF.

Autosomally inherited and affects both males and females

39
Q

What is haemophilia A?

A

X-linked, factor 8 deficiency

40
Q

What is haemophilia B?

A

X-linked, factor 9 deficiency

41
Q

What is thrombosis?

A

The formation of a blood clot within an intact blood vessel.

This usually results in obstruction of the blood flow with serious and possibly fatal consequences.

42
Q

What is Virchows triad?

A

3 contributory factors to thromobsis. They are:

  1. Blood
  2. Vessel wall
  3. Blood flow
43
Q

What changes in blood might increase the risk of venous thrombosis?

A
  1. Reduced levels of anticoagulant proteins
  2. Reduced fibinolytic activity
  3. Increased levels of clotting factors or platelets

Principles Of Medicine (34 decks)

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