Haemostasis

Question 1

Why clot?

Answer 1

Keeps blood in +pathogens out

Question 2

What triggers clotting?

Answer 2

Endothelium is anti-coagulant surface but INJURY exposes collagen which comes into contact w blood∴clot

Question 3

1ᵒ

Answer 3

🍽:
Adhere
Activate
Aggregate via fibrinogen –> 🔌

Question 4

2ᵒ

Answer 4

TF on the basement membrane indirectly activates thrombin (protease) –> cleaves fibrinogen →fibrin –>
forms insoluble mesh

Question 5

Models of clotting pathways?

Answer 5

• Old school cascade

- Cell based

Question 6

Process of 🍽 Adherence?

Answer 6

Endothelium⇶von Willebrand Factor which circulates After endothelial damage, endothelial cells have Weibel-Palade bodies⇶⇑ vWF, binds to exposed collagen + vWF receptors on 🍽 –> ACTIVATED 🍽 –> expresses functional fibrinogen receptors

Question 7

Process of 🍽 Activation?

Answer 7

• ACTIVATED 🍽 bind to fibrinogen –> aggregate ∴ linked

- 🍽⇶pro-activation/aggregation signalling ∞ eg ADP + thromboxane A2 (TXA2)

Question 8

Process of 🍽 Aggregation?

Answer 8

🍽 that haven’t seen wound activated by other.. more 🍽 will follow

Question 9

What’s Tissue Factor TF?

Answer 9

Sub-endothelial trigger for the coagulation cascade to initiate burst of haemostasis

Question 10

Process of Amplification in 2ᵒ?

Answer 10

Factor VIIa binds to TF –> prothrombin → thrombin –> activates receptors on 🍽 + endothelium –> amplifies aggregation + initiates ⇶vWF

Question 11

Role of Thrombin in 2ᵒ?

Answer 11

Activates cofactors: Factor VIIIa + Factor Va - forms Ca2+dependent complexes on 🍽 surface w:
Factor Xa - prothrombinase
Factor IXa - tenase

Question 12

Role of Factor Xa + IXa complexes?

Answer 12

• ↑ production of Factor Xa + thrombin - amplification stage of the coagulation cascade
• ↑ production of thrombin

Question 13

Process of Fibrinolysis?

Answer 13

tissue plasminogen activator tPA cleaves plasminogen → plasmin –> breaks down fibrin mesh→fibrin frag + D-dimers

Question 14

How to tell if clot is formed recently?

Answer 14

Measure levels of D-dimers

Question 15

Clot-busting💊?

Answer 15

tPA

Question 16

Mutated Factor VIII?

Answer 16

Haemophilia A 80%

Question 17

Mutated Factor IX?

Answer 17

Haemophilia B 20%

Question 18

What’s Haemophilia?

Answer 18

Failing to clot ∵ coagulation factor mutation

Question 19

What’s Thrombosis?

Answer 19

Clotting in wrong place

Question 20

Eg of arterial thrombosis?

Answer 20

Stroke

Question 21

Eg of venous thrombosis?

Answer 21

Deep Vein Thrombosis DVT

Question 22

What’s Disseminated intravascular coagulation DIC?

Answer 22

Whole body clots∵depletion of clotting factors + platelets –>bleeding

Question 23

Eg of DIC?

Answer 23

Sepsis - injures own tissues + organs

Question 24

Why’s coagulation activated in Sepsis?

Answer 24

• Coagulation🐟 vital to remove pathogens
• TF triggers coagulation independent signaling pathways mediated by protease activated receptors (PARs) on immune cells
• PAR dependent signals evoke pro-,anti-inflammatory pathways that regulate migration + proliferation of immune cells
• “Containment hypothesis”-coagulation ↑pathogen clearance by forming physical barrier