Haemostasis

Question 1

why is haemostasis needed in blood?

Answer 1

1. Coagulation following injury
2. Prevention of extreme blood clotting (thrombosis)
3. Fibrinolysis

Question 2

What are the actions taken by the body to ‘halt’ the blood following trauma?

Answer 2

• 3 intertwined processes
  1) Vasoconstriction
  2) primary haemostasis (unstable platelet plug)
  3) secondary haemostasis/coagulation (fibrin clot)
• fibrin clot binds to platelet plug

Question 3

Why is it important to understand these mechanisms?

Answer 3

• blood disorders
• risks of thrombosis
• treat thrombotic disorders
• monitor drug involved in bleeding
• control bleeding in general pop

Question 4

what are the steps that happen in response to injury?

Answer 4

Vasoconstriction → primary haemostasis → secondary haemostasis → fibrinolysis

Question 5

what two processes does primary haemostats involve?

Answer 5

• platelet adhesion

- platelet aggregation

Question 6

what process does secondary haemostasis involve?

Answer 6

-formation of a fibrin clot (coagulation)

Question 7

what does fibrinolysis involve?

Answer 7

dissolution of the blood clot

Question 8

where are platelets derived from?

Answer 8

myeloid stem cells

Question 9

what are the key features of platelets?

Answer 9

• discoid
• non-nucleated (classified as cell fragments)
• granule-containing (alpha + dense granules)

Question 10

describe the process fo platelet adhesion (primary haemostasis part 1)

Answer 10

platelets stick to damaged endothelium following injury through one of two ways:

1) direct → glycoprotein-Ia (GPIa) receptor binding to collagen
2) indirect → GPIb + Von Willebrand factor binds to collagen

Question 11

what does platelet adhesion cause?

Answer 11

1) activation
2) change in shape from disc → rounded with spicules (encourages interaction)
3) release action

Question 12

what happens during the platelet release action?

Answer 12

after it is activated, releases contents of storage granules:

1) ADP
2) fibrinogen
3) von Willebrand factor
4) A2 thromboxane

Question 13

what is the role of A2 thromboxane?

Answer 13

• causes positive feedback in platelet recruitment + aggregation
• vasoconstrictor

Question 14

what happens during platelet aggregation?

Answer 14

A2 thromboxane + ADP → platelet activation → conformational change in receptors so fibrinogen can bind (ADP can expose a receptor which enables platelets to link together) → link platelets together

Question 15

how is inappropriate platelet aggregation avoided?

Answer 15

• prostacyclin (powerful vasodilator)

- active blood flow

Question 16

give two examples of antiplatelet drugs

Answer 16

1) aspirin → reduced platelet aggregation

2) clopidogrel → block ADP receptor

Question 17

what is the role of Von Willebrand factor?

Answer 17

• glycoprotein
  1) mediates the adhesion of platelets to sites of injury (indirect platelet adhesion)

2)promotes platelet-platelet aggregation

Question 18

when is secondary haemostasis (coagulation) needed?

Answer 18

in larger vessels, platelet plug not strong enough so fibrin needed to stabilise it

Question 19

where are clotting factors synthesised?

Answer 19

-liver (except VWF + VIII made in endothelial cells)

Question 20

what three steps are involved in the synthesis of clotting factors?

Answer 20

initiation → amplification → propagation

Question 21

give three examples of 3 artificial anticoagulants

Answer 21

1) Heparin → Incr. antithrombin
2) Warfarin → Interfere with carboxylation
3) DOACs → Inhibit either thrombin or factor Xa

Question 22

give three examples of 3 natural anticoagulants

Answer 22

• ensures coagulation is confined to site of injury
  1. antithrombin → inhibits thrombin + factor Xa
  2. protein C → becomes APC
  3. protein S → acts as a co-factor with activated protein C (APC)

Question 23

what is the primary fibrinolytic enzyme?

Answer 23

plasmin (circulates in the form on plasminogen)

Question 24

give a summary of secondary haemostasis

Answer 24

fibrinogen released by the platelets to fibrin using thrombin (preactivated form called prothrombin)

Question 25

how is plasminogen activated to plasmin?

Answer 25

- tissue plasminogen activator | - plasminogen binding to lysine residues on fibrin clot

Question 26

what are the products of fibrin breakdown?

Answer 26

fibrin depredation products (FDP)

Question 27

how does tranexamic acid (and antifibrolytic drug) work?

Answer 27

- derivative of lysine - competetive inhibitor of lysine so plasminogen can not bind to lysine - can not be activated to plasmin so reduced no of enzymes (plasmin) are produced to breakdown fibrin clot

Question 28

what are the two different test of coagulation?

Answer 28

1) measuring the integrity of the extrinsic pathway (prothrombin time) 2) measuring the integrity of the extrinsic pathway (APTT)

Question 29

What can cause an imbalance in haemostasis therefore a bleed?

Answer 29

1) Reduced platelet number/function (primary) 2) Reduction in coagulation factors (secondary) → VWF reduction = VW disease → Haemophilia A + B → Cause? Liver disease, anticoagulants, DIC (uncontrolled coagulation activation) 3) Incr. fibrinolysis → Cause? DIC, thrombolytic therapy

Question 30

how is the risk increased for venous thrombosis?

Answer 30

1) Reduced no. of anticoagulants ie. antithrombin 2) reduced levels of fibrinolysis (e.g. in prganancy) 2) Incr. clotting factors/platelets (i.e. Factor VIII incr during preganancy, mutation, myeloproliferative disorders)

Question 31

how is the risk increased for venous thrombosis?

Answer 31

1) Reduced no. of anticoagulants ie. antithrombin so more likely for coagulation to happen therefore more likely thrombosis 2) reduced levels of fibrinolysis (e.g. in prganancy) 2) Incr. clotting factors/platelets (i.e. Factor VIII incr during preganancy, mutation, myeloproliferative disorders)