Haemostasis Flashcards
Describe primary haemostasis (in detail)
Constitutive release - vWF stored in Weibel-Palade bodies are released upon activation of endothelium
vWF is released normally in small amounts
Vessel endothelial damage = collagen exposed to blood components
vWF in blood binds to collagen
Normal platelets express collagen receptors and vWF receptors - they become activated when collagen and vWF bind
Activated platelets - express fibrinogen receptors (important for aggregation as they link platelets together via fibrinogen), release pro-activation signalling molecules e.g. ADP and TXA2 –> amplify aggregation and adhesion
Platelets link together by fibrin (from fibrinogen) and form platelet plug
Describe the activation of platelet step in haemostasis
Platelets are activated by collagen binding or vWF binding to their respective receptors on platelet
Activated platelets release pro-activation and aggregation signalling molecules e.g. ADP and TXA2
- these molecules amplify aggregation and adhesion
Activated platelets also express functional fibrinogen receptors - bind fibrinogen and link platelets together using fibrin (important for aggregation)
Describe the role of tissue factor in secondary haemostasis
TF is expressed by all sub-endothelial cells
It activates the coagulation cascade
Factor VIIa + TF = conversion of prothrombin -> thrombin
Describe the role of thrombin in secondary haemostasis
Thrombin activates receptors on platelets and endothelium = amplifies platelet aggregation and initiates release of stored vWF (from Weibe-Palade bodies in endothelium)
Activates co-factors = FVIIIa and FVa
- form calcium-dependent complexes on the surface of platelets
- with FXa = prothrombinase complex
- with FIXa = tenase complex
Known as the amplification stage as thrombin increases overall)
What are the steps of fibrinolysis?
- Release of plasminogen activators
- Plasmin production
- Clot lysis
Describe the role of plasminogen activators in fibrinolysis. How are they released? What do they do?
Injured endothelial cells express tPA (tissue plasminogen activator)
- this converts plasminogen to plasmin
- plasmin breaks down fibrin
- exposure of matrix proteins –> activation of FXII
Describe the role of plasmin in fibrinolysis. How is it produced? What does it do?
Plasminogen is cleaved into plasmin by tPA + fibrin binding with it
Plasmin breaks down crosslinks between the fibrin –> fibrin fragments (FDPs - fibrin degradation products)
Describe the process of clot lysis in fibrinolysis
Plasmin breaks cross-linked fibrin - releasing X-oligomers (smallest = D-dimer)
All FDPs can be used in labs as markers for fibrinolysis
Why do we need clotting?
- stop bleeding at site of injury (localised clotting)
- prevent blood loss (by formation of platelet plug)
Discuss haemophilia
- genetic disorder
- impairs body ability of making blood clots
- longer bleeding time after an injury (e.g. in joints or brain)
- due to mutations in coagulation factors
- Haemophilia A = FVIII (most common)
- Haemophillia B = FIX
Discuss thrombosis
- formation of blood clot in wrong location e.g. blood vessel - arterial or venous
- arterial thrombosis e.g. stroke = can develop in any artery in body, restricts/blocks blood flow to area
- venous thrombosis e.g. DVT = leg, can cause swelling (odeoma) and skin changes
Discuss disseminated intravascular coagulation (DIC)
- blood clots form throughout body (e.g. in sepsis)
- can injure tissues/organs
- leads to a depletion in clotting factors and platelets as they are being used up = bleeding
- use FDPs and D-dimers to diagnose as well as coagulation timing
Sepsis (as example):
- coagulation is needed in sepsis to create a physical barrier to pathogens = ‘containment hypothesis’
- TF triggers coagulation independent signalling pathways (mediated by PARs)
- PAR-dependent signals stimulate pro- and anti-inflammatory pathways
- these pathways regulate migration and proliferation of immune cells
