Lecture 2: Haemostasis

Question 1

What does von willebrand factor do?

Answer 1

Secreted by the endothelium when it is injured

Question 2

How many platelets come from a single megakaryocyte?

Answer 2

4000

Question 3

How big are platelets?

Answer 3

3uM by 0.5uM

Question 4

What happens when platelets are activated?

Answer 4

exocytosis, change of shape, increased respiratory rate

Adhesion- to exposed collagen
Activation- exocytosis of dense granules, serotonin, ADP and Ca
Aggregation- stimulated by ADP by fibrinogen (blocked by prasugrel)

Question 5

How are platelets activated?

Answer 5

Extracellular ADP –> activation of P2Y receptor –> cation flow

Platelets release thromboxane A2 (vasoconstrictor)

ADP is positive feedback

Question 6

What is the difference between plasma and serum?

Answer 6

Plasma is the fluid portion of blood, whereas serum is the fluid remaining after clotting

Question 7

Overview intrinsic vs extrinsic cascades

Answer 7

Extrinsic- tissue factor pathway- requires TF to occur- initiation of coagulation

Intrinsic- contact activation- all factors are already in place- amplification of the process through positive feedback

Question 8

What factors activate thrombin?

Answer 8

Xa and Va

Question 9

How is factor X activated to Xa?

Answer 9

Extrinsic Xase (TF and factor VIIa)

Intrinsic Xase (factor VIIIa and factor IXa)

Thrombin

Question 10

What are the prothrombin group factors?

Answer 10

Factors II, VII, IX, X

These are enzymes, vitamin K needed for synthesis, require Ca for activation, stable

Question 11

What are the thrombin group factors?

Answer 11

Factors I, V and VIII

Thrombin activates them, V and VIII are co-factors, factor I is fibrinogen, increased in inflammation, pregnancy and with oral contraceptives

Question 12

What is plasmin?

Answer 12

Lyses fibrin - stops/destroys clots

Starts as inactive plasminogen (made by liver)

Requires tissue Plasminogen activator (tPA) to mature - tPA is on the surface of endothelial cells

Question 13

What is protein C?

Answer 13

Coagulation inhibitor

Starts as inactive enzyme, made in the liver, activated on the surface of endothelial cells

Inactivates factor Va and VIIIa

Works with co-factor protein S to inactivate Va

Question 14

What is antithrombin III?

Answer 14

Peptide made in the liver

Blocks the activity of thrombin (and of Xa and IXa)

Heparin –> increases ATIII activity

Question 15

Overview of vitamin K deficiency

Answer 15

Results in clotting insufficiency

Rare bc vit K made by bacteria of large intestine and in leafy green vegetables

Caused by GI disease or no fat absorption: liver disease –> no bile salts

Warfarin prevents recycling of vit K

Question 16

What causes haemophilia A?

Answer 16

Lack of factor VIII

haemophilia B - lack of factor IX

Question 17

What are the anti-platelets?

Answer 17

Prevent clotting in the arteries

Asprin: COX inhibitor, blocks formations of thromboxane A2 in platelets, lengthens bleeding time, doesn’t increase coagulation time

ADP inhibitors: prasugrel/clopidogrel

Question 18

What are the anti-coagulants?

Answer 18

Prevent clotting in the veins

Heparins: inhibit coagulation (with ATIII) by inhibiting factor Xa

NOACs: dabigatran (thrombin inhibitor) and rivaroxaban (factor Xa inhibitor)

Warfarin: vitamin K antagonist, slow onset, requires monitoring

Question 19

What are the fibrinolytics?

Answer 19

Clotting in arteries (high pressure)

tPA, streptokinase, urokinase