Lecture 2: Haemostasis

Question 1

what do endothelial cells do

Answer 1

• when intact, prevents clots
• when injured, promotes local clotting
• signals inflammatory cells to areas needing defence / repair

Question 2

what is haemostasis

Answer 2

• stopping bleeding
• clotting and stopping blood from escaping
• first stage of wound healing

Question 3

what are the platelet based pathways to repair blood vessels

Answer 3

• platelet adhesion
• platelet activation
• platelet aggregation

Question 4

what are the non platelet based pathways of haemostasis

Answer 4

• enzyme cascade of coagulation

- vasoconstriction

Question 5

what are the vasoconstrictors released by platelets

Answer 5

• serotonin
• ADP
• thromboxane A2

Question 6

where are megakaryocytes found

Answer 6

bone marrow

Question 7

what is low platelet count called

Answer 7

thrombocytopaenia

Question 8

what happens during platelet activation

Answer 8

• platelets exocytose serotonin, ADP and calcium
• increase respiratory rate
• change shape to have protruding pseudopodia

Question 9

what do platelets adhere to

Answer 9

exposed collagen

Question 10

what is aggregation stimulated by

Answer 10

ADP

Question 11

what is aggregation blocked by

Answer 11

Prasugrel

Question 12

how do platelets aggregate

Answer 12

via fibrinogen

Question 13

which clotting factors are not enzymes

Answer 13

factor V and VIII, as they are cofactors

Question 14

what is an example of a thrombus

Answer 14

atrial fibrillation leads to thrombosis which leads to a stroke

Question 15

what are examples of anticoagulants

Answer 15

• heparin

- citrate

Question 16

what is serum and how is it different to plasma

Answer 16

• fluid left in blood after clotting

- lacks fibrinogen, clotting factors II, V and VIII

Question 17

what does the extrinsic pathway of coagulation do and require

Answer 17

• requires secretion of tissue factor

- initiates coagulation

Question 18

what does the intrinsic pathway of coagulation do

Answer 18

• all factors / proenzymes are already in place

- amplifies process through positive feedback

Question 19

which factors activate thrombin

Answer 19

• factor Xa poorly activates it

- factor Va and Xa together activate thrombin well

Question 20

what are the pathways to activate factor X

Answer 20

• extrinsic Xase enzyme
• intrinsic Xase enzyme
• thrombin through positive feedback

Question 21

what is extrinsic Xase

Answer 21

tissue factor + factor VIIa

Question 22

what is intrinsic Xase

Answer 22

factor VIIIa + IXa

Question 23

which factors does thrombin activate

Answer 23

• factor VIII

- factor V

Question 24

where are clotting factors made

Answer 24

liver

Question 25

what is vitamin K

Answer 25

- a class of related fat-soluble vitamins - is required to synthesise prothrombin (II), VII, IX and X - essential for gamma carboxylation of clotting enzymes

Question 26

what is plasmin

Answer 26

- lyses fibrin to stop or destroy clots - starts as inactive plasminogen (made by liver) - requires tissue plasminogen activator on endothelial cells to mature

Question 27

what is protein C

Answer 27

- coagulation inhibitor - works with cofactor protein S to inactivate Va - inactivates factor VIIIa - activated on surface of endothelial cells

Question 28

what is antithrombin II

Answer 28

- works with heparin | - blocks activity of thrombin, Xa and IXa

Question 29

what reverses the effects of heparin

Answer 29

protamine sulfate

Question 30

what is haemophilia A caused by

Answer 30

- congenital lack of factor VIII | - X-linked so only males have symptoms

Question 31

what is haemophilia B caused by

Answer 31

- genetic defect in factor IX | - also called christmas disease

Question 32

what are symptoms of haemophilia A and B

Answer 32

- affects larger blood vessels in joints and muscles | - wounds that bleed for days

Question 33

what are pharmalogical controls of blood clotting

Answer 33

- anti-platelet agents generally for arterial disease - anti-coagulants generally for venous disease - fibrinolytics generally to dissolve fibrin in arterial disease

Question 34

what is aspirin

Answer 34

- anti-platelet agent - blocks formation of thromboxane A2 in platelets - lengthens bleeding time without lengthening coagulation time - used after myocardial infarction

Question 35

what are anticoagulant drugs and how do they work

Answer 35

- heparins inhibit factor Xa - dabigatran inhibits thrombin - rivaroxaban inhibits factor Xa - warfarin is a vitamin K antagonist

Question 36

examples of fibrinolytics

Answer 36

- tissue plasminogen activator - streptokinase - urokinase