Clotting

Question 1

What activates platelets?

Answer 1

Thrombin
Adenosine diphosphate
Thromboxane A2
Glycoprotein IIb/IIIa

Question 2

Which drugs inhibit which of the platelet activating mechanisms?

Answer 2

Thrombin inhibitors (heparin, Vit K)

Clopidogrel and ticagrelor inhibit adenosine diphosphate

Aspirin inhibits thromboxane A2

Glycoprotein IIb/IIIa inhibitors (tirofiban)

Question 3

Which molecules cause platelets to aggregate?

Answer 3

Thrombin

Fibrin

Question 4

What dissolves the clot?

Answer 4

Plasmin

Question 5

What is the intrinsic pathway of the coagulation cascade?

Answer 5

Factor XII activates factor XI

Factor XIa activates factor IX

Factor IX groups with VIIIa (activated by VII) to activate factor X

COMMON PATHWAY

Question 6

Which coagulation factors are made in the liver?

Answer 6

2, 7, 9 and 10

Question 7

What is the extrinsic pathway of the coagulation cascade?

Answer 7

Factor VII, tissue factor, platelet and calcium activate factor X

Question 8

What is the common part of the coagulation cascade?

Answer 8

Factor X, V, platelets and calcium activate prothrombin to thrombin.

Thrombin then activate fibrinogen to fibrin.

BOOM

Question 9

What does the PT measure?

Answer 9

The time for the extrinsic pathway, normal 12seconds

Question 10

What is APTT?

Answer 10

It measures the intrinsic pathway of coagulation, 42seconds

Question 11

When is PT elevated?

Answer 11

Liver disease

Question 12

What do we use PT to monitor?

Answer 12

Warfarin

Question 13

Which time do we use to measure unfractioned heparin?

Answer 13

APTT

Question 14

Which diseases can APTT pick up?

Answer 14

Haemophilia

vWB

Question 15

When is the extrinsic pathway activated?

Answer 15

In external trauma and large bleeds

Question 16

When is the intrinsic pathway activated?

Answer 16

In internal vascular trauma, platelets activate this

Question 17

Which pathway uses factor VII?

Answer 17

Extrinsic

Question 18

What is weird about factor VIII and IX deficiency?

Answer 18

These patients bleed when really you’d think the extrinsic pathway would compensate like it does in XII deficiency

Question 19

Which cells have tissue factor?

Answer 19

Fibroblasts

Macrophages

Question 20

Where do TF cells live?

Answer 20

Outside the vascular system so they can work extrinsically

Question 21

What do PS and PE do?

Answer 21

These are phospholipids inside the cell membranes of coagulation cells

Question 22

What is Flippase and Floppase?

Answer 22

They flip PS and PE to outside the cell membrane and shit starts to happen

Question 23

How does the blood know where the clotting will take place?

Answer 23

Factor X only works with TF.

TF only exists on the cell that has been exposed by the vascular trauma

Question 24

What are the three stages of haemostasis?

Answer 24

Initiation
Amplification
Propagation

Question 25

What is the initiation stage?

Answer 25

The cut in the endothelial wall exposes a TF holding cell. TF binds to VII, and together they activate X, which activates V, which causes a small amount of thrombin to be made.

Question 26

What is the amplification stage?

Answer 26

If the cut on the wall is big enough, the thrombin will activate the platelets. These will then activate the intrinsic pathway on the platelet surface, starting with VII.

Question 27

What is propagation?

Answer 27

The intrinsic pathway will occur at the platelet surface and there will be large amounts of thrombin made, which splits fibrinogen into fibrin and the mesh clot can form.

Question 28

What is aspirin mechanism of action?

Answer 28

Thromboxane A2 antagonist

Question 29

What is clopidogrels mechanism of action?

Answer 29

Adenosine diphosphate inhibitor

Question 30

What do glycoproteins do re platelets?

Answer 30

They gather platelets together and help them stick.

Question 31

What do serum protease inhibitors do?

Answer 31

Inhibit excess clot formation

Question 32

What does healthy endothelium secrete to keep clotting under control?

Answer 32

Thrombomodulin (TM) This combines with thrombin and then aPC attaches and this cleaves any indication of clot forming. This stops unwanted clots

Question 33

What is fibrinolysis?

Answer 33

Break down of clots

Question 34

What starts the fibrinolysis cascade?

Answer 34

Plasminogen from the liver, is activated by tissue-Plasminogen Activator to plasmin.

Question 35

When does t-PA start working?

Answer 35

Only when there is damaged endothelium - so they are local and tPA is released when thrombin is present

Question 36

What does fibrinolysis release?

Answer 36

Fibrinolysis Degradation Products (FDP) | D-Dimer

Question 37

What is D-dimer?

Answer 37

A marker of clot breakdown as it is a product of fibrin degradation

Question 38

How do FDPs feedback?

Answer 38

Negative feedback, inhibiting further blood clotting

Question 39

What is an example of a thrombolytic?

Answer 39

Urokinase | Streptokinase

Question 40

Give an example of anti-fibrinolytic

Answer 40

Tranexamic acid

Question 41

What is tranexamic acid?

Answer 41

An anti-fibrinolytic | Stops the breakdown of clots