Haemostasis Flashcards
Why clot?
Keeps blood in +pathogens out
What triggers clotting?
Endothelium is anti-coagulant surface but INJURY exposes collagen which comes into contact w blood∴clot
1ᵒ
🍽:
Adhere
Activate
Aggregate via fibrinogen –> 🔌
2ᵒ
TF on the basement membrane indirectly activates thrombin (protease) –> cleaves fibrinogen →fibrin –>
forms insoluble mesh
Models of clotting pathways?
- Old school cascade
- Cell based
Process of 🍽 Adherence?
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
Process of 🍽 Activation?
- ACTIVATED 🍽 bind to fibrinogen –> aggregate ∴ linked
- 🍽⇶pro-activation/aggregation signalling ∞ eg ADP + thromboxane A2 (TXA2)
Process of 🍽 Aggregation?
🍽 that haven’t seen wound activated by other.. more 🍽 will follow
What’s Tissue Factor TF?
Sub-endothelial trigger for the coagulation cascade to initiate burst of haemostasis
Process of Amplification in 2ᵒ?
Factor VIIa binds to TF –> prothrombin → thrombin –> activates receptors on 🍽 + endothelium –> amplifies aggregation + initiates ⇶vWF
Role of Thrombin in 2ᵒ?
Activates cofactors: Factor VIIIa + Factor Va - forms Ca2+dependent complexes on 🍽 surface w:
Factor Xa - prothrombinase
Factor IXa - tenase
Role of Factor Xa + IXa complexes?
- ↑ production of Factor Xa + thrombin - amplification stage of the coagulation cascade
- ↑ production of thrombin
Process of Fibrinolysis?
tissue plasminogen activator tPA cleaves plasminogen → plasmin –> breaks down fibrin mesh→fibrin frag + D-dimers
How to tell if clot is formed recently?
Measure levels of D-dimers
Clot-busting💊?
tPA
Mutated Factor VIII?
Haemophilia A 80%
Mutated Factor IX?
Haemophilia B 20%
What’s Haemophilia?
Failing to clot ∵ coagulation factor mutation
What’s Thrombosis?
Clotting in wrong place
Eg of arterial thrombosis?
Stroke
Eg of venous thrombosis?
Deep Vein Thrombosis DVT
What’s Disseminated intravascular coagulation DIC?
Whole body clots∵depletion of clotting factors + platelets –>bleeding
Eg of DIC?
Sepsis - injures own tissues + organs
Why’s coagulation activated in Sepsis?
- 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
