29 - Haemostasis Flashcards

1
Q

Primary haemostasis
1)
2)
3)

A

1) Vasoconstriction
2) Platelet adhesion
3) Platelet aggregation

Occurs seconds to minutes after injury

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2
Q

Secondary haemostasis
1)
2)

A

1) Activation of coagulation factors
2) Formation of fibrin

Occurs minutes after injury

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3
Q

Fibrinolysis

A

1) Activation of fibrinolysis
2) Lysis of blood clot

Occurs minutes to hours after injury

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4
Q

Virchow’s triad
1)
2)
3)

A
Description of inappropriate clotting (thrombosis)
Factors that can lead to thrombosis are:
1) Blood composition
2) Vessel wall
3) Blood flow
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5
Q

How is functional integrity of vascular wall tested?

A

It can’t be tested at the moment. No functional test

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6
Q

Coagulation system aspects
1)
2)
3)

A

1) Complex system of proteins in plasma
2) Interact with platelets and blood vessel wall
3) Clotting and bleeding are opposite ends of spectrum

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7
Q

Starter of the coagulation cascade

A

Tissue factor (TF) released by damaged epithelial cells

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8
Q

Key enzyme in coagulation cascade that must be controllled

A

Thrombin

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9
Q
Initiation phase of coagulation 
1)
2)
3)
4)
A

1) Blood vessel wall injured, tissue factor is exposed.
2) TF binds FVIIa, or binds FVII and converts it to FVIIa
3) TF/FVIIa complex activates FIX and FX.
4) FXa binds to FVa on cell surface

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10
Q
Amplification phase of coagulation 
1)
2)
3)
4)
A

1) FXa/FVa complex bound to endothelial wall converts small amounts of prothrombin to thrombin
2) Small amount of generated thrombin activates FV, FVIII, FXI and local platelets
3) FXIa converts FIX to FIXa (activated)
4) Activated platelets bind to FVa, FVIIIa, FIXa

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11
Q

Propagation phase of coagulation
1)
2)
3)

A

1) FXIIIa/FIXa complex on platelets activates FX on the surface of active platelets
2) FXa and FVa convert large amounts of prothrombin to thrombin in ‘thrombin burst’
3) Thrombin burst leads to stable formation of fibrin clot

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12
Q

Factors that convert prothrombin to thrombin

A

FXa and FVa in association with each other

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13
Q

Thrombin funciton

A

Converts fibrinogen to fibrin.
Activates platelets.
Can negatively-regulate upstream factors in coagulation cascade

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14
Q

Thrombin inactivation

A

Thrombomodulin-APC binds thrombin, regulates ability to cleave fibrinogen.

Irreversibly inhibited by antithrombin (process increased x1000 by heparin)

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15
Q

Non-coagulation roles of thrombin
1)
2)
3)

A

1) Activates protease-activated receptors (PARs)
2) Involved in angiogenesis, inflammation, atherosclerosis, neutrophil, monocyte migration
3) Could be involved in tumour spread

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16
Q

Caveat to haemostatic testing

A

Not reflective of physiology

17
Q

Three broad types of haemostatic testing

A

1) Predict bleeding
2) Predict clotting
3) Monitor drugs used to manipulate haemostatic system

18
Q

Haemostatic tests on platelets

A

Look at number, function, appearance

19
Q

Are there global tests for risk of bleeding?

A

Yes

20
Q

Are there global tests for risk of clotting?

A

No

21
Q

Are there global tests to monitor anticoagulant drugs?

A

Yes

22
Q

Are there specific assays for risk of bleeding?

A

Yes

23
Q

Are there specific assays for risk of clotting?

A

Yes

24
Q

Are there specific assays to monitor anticoagulant dugs?

A

Yes

25
Q

Things involved in haemostasis that can be genetically tested

A

Risk of clotting, bleeding disorders. Maybe different genotypes react differently to anticoagulant drugs.

26
Q
Key principles for coagulation tests
1)
2)
3)
4)
5)
A

1) Sample integrity is crucial (EG: can’t have too little blood in sample)
2) Standard curves made
3) Control samples
4) Duplicate testing
5) Multiple consistent tests before diagnosing a patient

27
Q

Global tests for bleeding
1)
2)
3)

A

1) APTT
2) PT
3) Thrombin generation

28
Q

APTT

A
Activated Partial Thromboplastin Time
Take blood at 37 degrees.
Add Ca2+ to reverse citrate in tube.
Measure time for fibrin to form.  
Tests cascade from FXII to fibrin
29
Q

PT

A

Prothrombin time.
Add Ca2+ to reverse citrate in tube
Thromboplastin activated.
Tests cascade from FVII to fibrin

30
Q

Bleeding test used to test effect of heparin

A

Activated partial thromboplastin time (APTT)

31
Q

Bleeding test used to monitor warfarin

A

Prothrombin time (PT) test

32
Q

Examples of specific tests for bleeding
1)
2)
3)

A

1) Factor assays
2) Collagen assays
3) Fibrinogen assay

33
Q

Pros and cons of functional clot-based assays

A

Better reflect physiology, but are technically difficult to perform.

34
Q

Pros and cons of chromogenic assays

A

More reproducible, but questionable clinical relevance quesitonable

35
Q

Problems with global tests

A

Each lab does it slightly differently with different reagents.

36
Q

Solution to differing reagents used between labs on global assays

A

Make international normalised ratio (INI), which is PT result/average of PT results from lab. This fraction is then raised to the power of ISI (international sensitivity index), based on which reagents were used.

37
Q

Example of a global functional assay

A

APTT.

Factor deficiency, lupus anticoagulant, heparin monitoring

38
Q

Example of a specific factor assay

A

FXIII assay

39
Q

Example of a chromogenic assay

A

Anti-FXa assay.

For heparin monitoring.