Haemostasis II - Lecture 6

Question 1

What are the steps of haemostasis following vascualr injury?

Answer 1

1. Blood vessel response- vasoconstriction
2. Activation of platelets and formation of platelet plug
3. Blood coagulation- intrinsic and extrinsic pathways
4. Clot retraction and fibrinolysis Steps 2-4 mediated by key molecule, thrombin (to help fibrinogen to create a fibrin mesh to hold down the platelet aggregate)

Question 2

Describe the extrinsic pathway

Answer 2

Initiation stage of coagulation. Extrinsic pathway allows to generate small amount of thrombin

Exposure of tissue factor (TF)(F3) from damage of endothelium➡️ TF binds to circulating F7➡️ activation into F7a➡️ F10 activation by F6a and Ca2+ turning it into F10a➡️ F10a, phosphatidyl serine, Ca2+, F5a activates prothrombin➡️ makes thrombin

Question 3

Describe the intrinsic pathway

Answer 3

Intrinsic pathway is to generate large amount of thrombin

Amplification stage of coagulation

Tissue damage activates F12 to F12a➡️ F12a + F11 form F11a➡️ F11a + F9 form F9a➡️ F9a + F8a, Ca2+, phosphatidylserine activates F10 into F10a➡️ F10a and F5a, Ca2+, phosphatidyl serine activate prothrombin to thrombin

Question 4

What does thrombin do?

Answer 4

Thrombin helps drives its own generation by activating F11, F8a, F5a, F7a. After a while it will generate negative factors which stop production of thrombin

Thrombin directly activates fibrinogen to fibrin and activates F3 to F3a which helps cross linking into a fibrin mesh

It activates platelets which provide a pro-coagulation surface by flipping phosphatidyl serine which forms a Ca2+, F10a, F5a complex that supports thrombin

Question 5

What is Virchows triad?

Answer 5

3 common factors that lead to thrombus formation

Stasis of blood flow- most prominent (stopping blood flow)

Hypercoagulability- abnormalities in coagulation cascade or platelet activation

Endothelial injury

Question 6

Name some disorders involving platelets

Answer 6

Do full blood counts form a blood sample to look at counts of cells.

Low platelet count-thrombocytopenia

High platelet count- thrombocytosis

Platelets can also be macro or micro in each case

Question 7

What can cause changes in platelet count?

Answer 7

Low count could be due to low production (B12 deficiency, viral infection, toxic chemicals, alcohol, leukaemia or inherited thrombocytopenia) or high destruction (some medications, autoimmune, pregnancy, bacterial infection, inherited thrombocytopenia or autoimmune disorders)

Increased count- mutations in progenitors, chronic inflammation, cancer or inherited mutations in progenitors

Question 8

How would you test platelet function?

Answer 8

Light transmission aggregometry- as platelets clump together more light is let through (less cloudy) after initial activation and change shape

Light transmission aggregometry (LTA) is used to assess defects in platelet function

Common agonist used include- Integrilin causes loos of aggregation but retains shpae change. Collagen and collage related peptide on GP5, thrombin on PAR1,4, ADP on P2Y1 and P2Y12, TxA2 analogue U46619 on the TxA2 receptor

Aspirin blocks COX activity and stops arachadonic acid causing aggregation via the TxA2 pathway . U46619 can overcome this

Von willebrand factor alone does not cause aggregation, add Riscocetin leads to agglutination which does not activate alpha2b-beta3 integrin - Can block secretion