29 - Haemostasis

Question 1

Primary haemostasis
1)
2)
3)

Answer 1

1) Vasoconstriction
2) Platelet adhesion
3) Platelet aggregation

Occurs seconds to minutes after injury

Question 2

Secondary haemostasis
1)
2)

Answer 2

1) Activation of coagulation factors
2) Formation of fibrin

Occurs minutes after injury

Question 3

Fibrinolysis

Answer 3

1) Activation of fibrinolysis
2) Lysis of blood clot

Occurs minutes to hours after injury

Question 4

Virchow’s triad
1)
2)
3)

Answer 4

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

Question 5

How is functional integrity of vascular wall tested?

Answer 5

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

Question 6

Coagulation system aspects
1)
2)
3)

Answer 6

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

Question 7

Starter of the coagulation cascade

Answer 7

Tissue factor (TF) released by damaged epithelial cells

Question 8

Key enzyme in coagulation cascade that must be controllled

Answer 8

Thrombin

Question 9

Initiation phase of coagulation 
1)
2)
3)
4)

Answer 9

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

Question 10

Amplification phase of coagulation 
1)
2)
3)
4)

Answer 10

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

Question 11

Propagation phase of coagulation
1)
2)
3)

Answer 11

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

Question 12

Factors that convert prothrombin to thrombin

Answer 12

FXa and FVa in association with each other

Question 13

Thrombin funciton

Answer 13

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

Question 14

Thrombin inactivation

Answer 14

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

Irreversibly inhibited by antithrombin (process increased x1000 by heparin)

Question 15

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

Answer 15

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

Question 16

Caveat to haemostatic testing

Answer 16

Not reflective of physiology

Question 17

Three broad types of haemostatic testing

Answer 17

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

Question 18

Haemostatic tests on platelets

Answer 18

Look at number, function, appearance

Question 19

Are there global tests for risk of bleeding?

Answer 19

Yes

Question 20

Are there global tests for risk of clotting?

Answer 20

No

Question 21

Are there global tests to monitor anticoagulant drugs?

Answer 21

Yes

Question 22

Are there specific assays for risk of bleeding?

Answer 22

Yes

Question 23

Are there specific assays for risk of clotting?

Answer 23

Yes

Question 24

Are there specific assays to monitor anticoagulant dugs?

Answer 24

Yes

Question 25

Things involved in haemostasis that can be genetically tested

Answer 25

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

Question 26

``` Key principles for coagulation tests 1) 2) 3) 4) 5) ```

Answer 26

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

Question 27

Global tests for bleeding 1) 2) 3)

Answer 27

1) APTT 2) PT 3) Thrombin generation

Question 28

APTT

Answer 28

``` 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 ```

Question 29

PT

Answer 29

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

Question 30

Bleeding test used to test effect of heparin

Answer 30

Activated partial thromboplastin time (APTT)

Question 31

Bleeding test used to monitor warfarin

Answer 31

Prothrombin time (PT) test

Question 32

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

Answer 32

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

Question 33

Pros and cons of functional clot-based assays

Answer 33

Better reflect physiology, but are technically difficult to perform.

Question 34

Pros and cons of chromogenic assays

Answer 34

More reproducible, but questionable clinical relevance quesitonable

Question 35

Problems with global tests

Answer 35

Each lab does it slightly differently with different reagents.

Question 36

Solution to differing reagents used between labs on global assays

Answer 36

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.

Question 37

Example of a global functional assay

Answer 37

APTT. | Factor deficiency, lupus anticoagulant, heparin monitoring

Question 38

Example of a specific factor assay

Answer 38

FXIII assay

Question 39

Example of a chromogenic assay

Answer 39

Anti-FXa assay. | For heparin monitoring.