Notion Questions

Question 1

What is normal haemostatis a balance between?

Answer 1

Fibrinolytic factors + anticoagulant proteins and coagulant factors + platelets

Question 2

3 stages of haemostastis?

Answer 2

Vasoconstriction
Primary haemostasis- formation of unstable platelet plug at site of vessel wall damage
Secondary haemostasis/coagulation- Formation of stable fibrin clot which then leads to fibrinolysis

Question 3

How are platelets formed?

Answer 3

Formed in the bone marrow by the fragmentation of megakaryocyte cytoplasm, they are cresecent shaped, non-nucleated cells

Question 4

How do platelets interact with cells?

Answer 4

They stick to damaged endothelium cells via the GP1a receptor or VWF factor, this causes them to become more rounded with spicules to encourage platelet-platelet interaction

Question 5

Platelet release reaction?

Answer 5

Adhesion of platelets causes the contents of their granules to be released- alpha granules and dense granules release ADP, fibrinogen and von Willebrand factor

Question 6

Thromboxane A2?

Answer 6

Produced by activated platelets from arachidonic acid derived from the cell membrane
Important vasoconstrictor and increases platelet aggregation

Question 7

What do ADP and thromboxane A2 bind to?

Answer 7

P2Y12 and thromboxane A2 receptors

Question 8

What do platelets cause a conformational change in?

Answer 8

GPIIb/IIIa receptor which binds to fibrinogen, which links platelets together to form the platelet plug

Question 9

What is a powerful vasodilator that suppresses platelet activation?

Answer 9

Prostacyclin (PGI2)

Question 10

Effects of aspirin?

Answer 10

Irreversibly inhibits production of thromboxane A2 by blocking cylco-oxygenase

Question 11

Effects of clopidogrel?

Answer 11

Blocks ADP receptor P2Y12

Question 12

Von Willebrand Factor?

Answer 12

Glycoprotein that mediates adhesion of platelets and is a specific carrier for factor VIII

Question 13

Where are most clotting factors produced?

Answer 13

The liver

Question 14

What is each step in sequence of secondary haemostasis characterised by?

Answer 14

Conversion of an inactive zymogen (proenzyme) into an active clotting factor by splitting of peptide bonds

Question 15

What role do Ca2+ ions play?

Answer 15

Binding activated clotting factors to the phospholipid surfaces of platelets

Question 16

3 things that occur during the initiation phase?

Answer 16

TF gets exposed to blood due to injury
Factor VIIa binds to TF which activates factors IX to IXa and X to Xa
Prothrombin (Factor II) is activated to generate Factor IIa (thrombin)

Question 17

What happens during the amplification phase?

Answer 17

Small amount of thrombin activates co-factors V and VIII, zymogen factor XI and platelets

Question 18

3 things that happen during the propagation phase?

Answer 18

Factor XI converts more factor IX to IXa
IXa with Factor VIIIa amplifies the conversion of factor X to Xa
Rapid burst in thrombin generation which cleaves circulating fibrinogen to form the insoluble fibrin clot

Question 19

2 natural anticoagulant pathways?

Answer 19

Thrombin binds to thrombomodulin on endothelial cell surfaces to activate protein C. This inactivates factors Va and VIIIa with co-factor protein S
Thrombin and factor Xa are inactivated by antithrombin, which is markedly potentiated by heparin

Question 20

3 anticoagulant drugs?

Answer 20

Heparin- indirectly increases action of antithrombin
Warfarin- vitamin K antagonist that reduces synthesis of factors II, VII, IX and X, takes several days for effects
Direct Oral Anticoagulations (DOACs)- directly inhibit thrombin or factor Xa

Question 21

Fibrinolytic system?

Answer 21

Plasmin breaks down clots. Its inactivated form-plasminogen- is activated by tPa

Question 22

Thrombolytic therapy

Answer 22

Given intravenously to generate plasmin to lyse clots, high risk of bleeding

Question 23

Example of antifibrinolytic drug?

Answer 23

Tranexamic acid which binds to plasminogen and acts as a competitive inhibitor

Question 24

Extrinsic vs intrinsic pathways?

Answer 24

In endothelium vs in plasma

TF and factors VII, X, and co-factor V vs factors XII, XI, IX, X and co-factors VIII and V

Question 25

Prothrombin Time?

Answer 25

Measures integrity of extrinsic pathway

Prolonged time indicates a reduction in the activity of factors VII, X, V, II (prothrombin) or fibrinogen

Question 26

Activated partial thromboplastin time (APTT)?

Answer 26

Measures the integrity of the ‘intrinsic’ pathway
Performed by the contact activation of factor XII by a surface such as glass, or using a contact activator such as silica or kaolin.
An isolated prolonged APTT (i.e. normal PT) is seen in patients with haemophilia A (factor VIII deficiency), haemophilia B (factor IX deficiency) and factor XI deficiency. However this may also be caused by factor XII deficiency which does not result in bleeding. (Note that FXII does not appear in the cell-based model described in ‘Coagulation (secondary haemostasis): formation of the stable fibrin clot’ and is not important for clotting in vivo).

Question 27

Risk factors for venous thrombosis

Answer 27

Reduced levels of anticoagulant proteins
Reduced fibrinolytic activity, e.g inhibition of plasminogen during pregnancy
Increased levels of clotting factors or platelets, e.g Factors VIII and V and platelets