Haemostasis and Thrombosis

Question 1

Give examples of pro-coagulants

Answer 1

Prothrombin, F5, F7-13, fibrinogen

Question 2

Give examples of anti-coagulants

Answer 2

Plasminogen, TFPI (tissue factor pathway inhibitor), protein S and C, and antithrombin

Question 3

What’s the difference between venous and arterial thomboses?

Answer 3

Venous - red thrombi with high fibrin. The thrombus forms within blood vessel lumen
Arterial - white thrombi with high platelets. The thrombus forms within atherosclerotic plaque

Question 4

What is virchow’s triad?

Answer 4

1. rate of blood flow
2. consistency of blood
3. blood vessel wall integrity

Question 5

What are the different stages of cell based theory of coagulation?

Answer 5

1. initiation - small scale production of thrombin
2. amplification - large scale production of thrombin on platelet surfaces
3. propagation - generation of fibrin strands by thrombin

Question 6

What molecules target each of the stages of cell based theory of coagulation?

Answer 6

1. initiation is targeted by anti-coagulants
2. amplification is targeted by anti-platelets
3. propagation is targeted by thrombolytics

Question 7

What happens in the initiation step of coagulation?

Answer 7

Small scale thrombin production where:

• tissue factor bearing cells activate F10 and F5 forming the prothombinase complex
• this prothombinase complex activates F2 (prothrombin) forming thrombin
• antithrombin (AT-III) inactivates F10a and thrombin

Question 8

What are examples of anticoagulant drugs?

Answer 8

Dabigatran
Rivaroxaban
Heparin
Warfarin

Question 9

What does Dabigatran do? how is it administered?

Answer 9

Inhibits thrombin

Oral

Question 10

What does Rivaroxaban do? How is it administered?

Answer 10

inhibits F10a

oral

Question 11

What does Heparin do? How is it administered?

Answer 11

Activates AT III

IV, SC

Question 12

What is a low molecular weight version of heparin and how is it administered?

Answer 12

Dalteparin

SC

Question 13

Why would you use dalteparin instead of heparin?

Answer 13

Dalteparin is a LMW heparin and LMWHs have a more predictable response, a greater bioavailability, and a longer anti-Xa half life than unfractionated heparin

Question 14

What does warfarin do? How is it administered?

Answer 14

Vitamin K antagonist
Vitamin K creates F2, 7, 9 10
Oral

Question 15

Why would aspirin have a limited affect on DVTs during long haul flights?

Answer 15

Because they treat ARTERIAL thrombi

Question 16

What happens in the amplification stage of coagulation?

Answer 16

Large scale production of thrombin:
Thombin activates platelets in a +ve feedback effect
Activated platelets change shape and become ‘sticky’ and attach to other platelets

Question 17

How are platelets activated in coagulation?

Answer 17

1. thrombin binds to the protease activated receptor (PAR)
2. PAR activation -> rise in intracellular [Ca2+]
   Liberates arachidonic acid which turns into TXA2 by COX enzymes
   TXA2 induces expression of Glp2b/3a which aids platelet aggregation
3. raised [Ca2+] lead to exocytosis of ADP dense granules
4. ADP binds to another platelet’s P2Y to activate the platelet

Question 18

What are examples of antiplatelet drugs?

Answer 18

Clopidogrel
Aspirin
Abciximab

Question 19

How does clopidogrel work? how is it administered?

Answer 19

ADP/P2Y12R antagonist

Oral

Question 20

How does aspirin work? How is it administered?

Answer 20

Irreversible COX1 inhibitor

oral

Question 21

How does abciximab work? How is it administered?

Answer 21

Glp2b/3a antagonist

IV/SC

Question 22

What are indications for use of anticoagulant drugs?

Answer 22

DVT/Pe
Thrombosis during surgery
Atrial fibrillation - prophylactic to strokes]
VTE

Question 23

What are indications for use of antiplatelet drugs?

Answer 23

Acute coronary syndromes - MI
Atrial fibrillation - prophylaxis of strokes
ARTERIAL THROMBI

Question 24

What happens in the propagation step of coagulation?

Answer 24

Thrombin mediated generation of fibrin -
Activated platelets make a large scale production of thrombin
Thrombin then binds to fibrinogen and converts it to fibrin strands

Question 25

How are pre-formed clots removed using drugs

Answer 25

Use thrombolytics - anticoagulants and antiplatelets won't remove them

Question 26

What is an example of a thrombolytic drug and how does it work? How is it administered?

Answer 26

Recombinant tissue type plasminogen activator (rt-PA) A plasminogen analogue that converts plasminogen to plasmin and then degrades fibrin and dissolves the clot Oral

Question 27

What are indications for thrombolytic use?

Answer 27

Arterial thombi VTE Stroke - first line ST elevated MI

Question 28

What is a DVT? How is it caused?

Answer 28

A red thrombus of the deep veins of the leg eg a popliteal vein caused by stasis of blood and damage to the endothelium

Question 29

What is a PE

Answer 29

Thrombus attachment - pulmonary embolism causing a blood clot in the lungs

Question 30

What are ways to manage a DVT or PE

Answer 30

Reduce levels of anti-coagulant factors using anticoagulants eg dabigatran, rivaroxaban, heparin, warfarin

Question 31

What are NSTEMI and how are they caused?

Answer 31

Non ST Elevated MI caused by a white thrombus due to a partially occluded coronary artery leading to: - damage to endothelium - platelet aggregation - atheroma formation

Question 32

How are NSTEMI managed?

Answer 32

reduce the lipid formation and platelet aggregation/activation - antiplatelets eg clopidogrel, aspirin, abciximab

Question 33

What are STEMI and how are they caused?

Answer 33

ST Elevated MI due to a white thrombus and a fully occluded coronary artery due to: - damage to endothelium - atheroma formation - platelet aggregation

Question 34

How are STEMI managed?

Answer 34

Reduce lipid formation, platelet aggregation/activation and dissolve thrombus - antiplatelet and thrombolytics AP - clopidogrel, aspirin, adciximab TL - alteplase

Question 35

What are diseases associated with arterial thrombosis?

Answer 35

Brain - stroke Heart - acute coronary synromes eg AF Arteries - aortic aneurysm, peripheral arterial disease

Question 36

What are diseases associated with venous thrombosis?

Answer 36

DVT and PE

Question 37

What are treatment options of thrombosis if you think there is a clot?

Answer 37

Thrombolytic

Question 38

What are the treatment options of thrombosis if you suspect a clot in the future in venous system

Answer 38

Anticoagulant

Question 39

What are treatment options of thrombosis if you suspect a clot in the future in the arterial system

Answer 39

Antiplatelets