Haemostasis

Question 1

What is Haemostasis?

Answer 1

The process in which blood coagulation is initiated and terminated in a tightly regulated fashion together with the removal of the clot

Question 2

What is the first step of haemostasis?

Answer 2

Vasoconstriction restricts blood flow to the vessel

Question 3

What is primary haemostasis?

Answer 3

The second stage, platelet aggregation that forms a plug

Question 4

What is secondary haemostasis?

Answer 4

Generation of the enzyme thrombin that converts soluble fibrinogen to insoluble fibrin

Question 5

What is Fibrinolysis?

Answer 5

Removal of the clot

Question 6

What is the haemostatic system?

Answer 6

a mosaic of activating or inhibitory pathways

Question 7

What are the five major components of the haemostatic system?

Answer 7

Blood vessels
– Platelets
– Coagulation factors
– Coagulation inhibitors
– Fibrinolytic factors (clot dissolving components)

Question 8

Why must haemostasis be regulated?

Answer 8

to prevent inappropriate clot formation

Question 9

What can happen when blood vessels are blocked?

Answer 9

Restricting blood flow
Starving tissues of oxygen
Leading to cell death

Question 10

Where are platelets produced?

Answer 10

In the bone marrow

Question 11

Where are coagulation proteins produced?

Answer 11

Primarily made in the liver

Question 12

Why is haemostasis so rapid?

Answer 12

all the components are pre-synthesised and circulating in the blood

Question 13

How do activated platelets generate thrombin?

Answer 13

they expose a surface that promotes the assembly of complexes leading to local generation of thrombin

Question 14

What does the undisturbed endothelium present?

Answer 14

An anticoagulant response that dampens the activation of coagulation

Question 15

What does the anticoagulant response do?

Answer 15

limits spread of the response beyond the injury

Question 16

Where are platelets produced?

Answer 16

Bone marrow

Question 17

What is Thrombopoietin?

Answer 17

Glycoprotein that regulates the production of platelets

Question 18

What is thrombocytopenia?

Answer 18

Deficiency in circulating platelets due to decreased platelet formation

Question 19

What are megakaryocytes?

Answer 19

hematopoietic cells that are responsible for the production of platelets

Question 20

What is the purpose of the adhesion molecules found on the surface

Answer 20

To recognise components in the matrix e.g collagen and VWF

Question 21

What occurs when platelets bind to ligands? (such as collagen)

Answer 21

release of granules containing ADP and thromboxane that activates the platelet

Question 22

What does the exposure of phosphotidylserine (PS) on the platelet surface lead to?

Answer 22

The negatively charged surface promotes thrombin generation and fibrin deposition

Question 23

What occurs to VWF under sheer stress?

Answer 23

It unfolds, exposing platelet binding sites. These can then bind to platelets as they go past

Question 24

What does localised thrombin generation lead to?

Answer 24

further platelet activation and formation of a polymerised fibrin mesh

Question 25

What are zymogens?

Answer 25

serine proteases that travel in the blood and require cofactors to work effectively, they help assemble blood clots

Question 26

What is a tissue factor?

Answer 26

the trigger for blood coagulation, it’s a cell surface protein expressed on cells not in contact with the blood

Question 27

What is the initiation stage of the pro-coagulant response?

Answer 27

Vascular damage means that blood is then exposed to cells that express tissue factors, this then amplifies the volume of thrombin produced which can convert fibrinogen to fibrin

Question 28

What are some ways we can control the activation mechanism?

Answer 28

1) Shutting down the initiation complex after it has been activated
2) Reducing cofactors and activated proteases which reduces the generation of fibrin clots

Question 29

What is TFP1?

Answer 29

a protein that inactivates the initiation complex

Question 30

How can you do a lab assessment of clotting?

Answer 30

Centrifuge to prepare the plasma, then add Calcium to initiate clotting

Question 31

What is thrombosis?

Answer 31

The formation of an intravascular clot

Question 32

What does sweet clover poison do?

Answer 32

It is a competitive inhibitor of vitamin K, so prevents blood from clotting after an injury

Question 33

What are some treatments for blood loss?

Answer 33

Salt solution can expand the blood volume, or replace platelets/ cofactors/ coagulation factors

Question 34

What does Virchows triad explain?

Answer 34

explains pathophysiologic mechanisms leading to thrombosis

Question 35

How would liver disease have an effect on platelet production?

Answer 35

Platelet formation is regulated by the
hormone thrombopoietin produced by the
liver and kidney

Question 36

How does the autocrine effect of platelet activation work?

Answer 36

The platelet contains adhesion molecules that bind to VWF in the blood
the binding causes the release of ADP and thromboxane into the blood causing the platelet to become activated in an autocrine fashion

Question 37

Where is VWF found?

Answer 37

it is found in the broken endothelium (collagen of the skin)

Question 38

What does the exposure of the negatively charged surface on the platelet promote?

Answer 38

it promotes thrombin generation and fibrin deposition

Question 39

What kind of disease is VWF disease?

Answer 39

autosomal recessive

Question 40

How would you distinguish an activated factor?

Answer 40

has a small an next to its roman numerals

Question 41

Is the extrinsic or intrinsic coagulation pathway activated by tissue factor?

Answer 41

extrinsic

Question 42

How does the anticoagulant response work?

in terms of thrombin

Answer 42

Thrombin binds to thrombomodulin which activates the anticoagulant pathway
This then activates protein C which in turn with protein S rapidly inactivates both factor 8 and factor 5