Blood Coagulation Flashcards
What is Haemostasis?
Process in which blood coagulation is initiated and terminated
- stops bleeding at the site of injury
- whilst maintaining blood flow
Steps of haemostasis
1) Vasoconstriction limits blood flow to the damaged vessel
2) Platelet aggregation & plug formation (PRIMARY)
3) Generation of enzyme thrombin which proteolyzes the soluble fibrinogen into insoluble fibrin (SECONDARY)
4) Removal of the clot, fibrinolysis.
5 components of the haemostatic system
1) Blood vessels
2) Platelets
3) Coagulation factors
4) Coagulation inhibitors
5) Fibrinolytic factors
How is clotting so rapid?
- Platelets’ main function is to monitor vascular integrity and they circulate in large numbers
- Coagulation proteins made in liver
- Most components are pre-synthesised and already circulating in blood
How is clotting so localised?
- Platelets only sense proteins exposed at sites of vascular injury
- Thrombin is generated locally because of exposed surfaces
-Thrombin generation network is triggered by the exposure of blood to a cellular receptor normally anatomically separate from blood - Undisturbed endothelium has anticoagulant
How are platelets formed?
- anucleate cells produced in bone marrow
- platelet formation is regulated by the hormone thrombopoietin
- platelets are formed by the budding off from megakaryocytes
Resting platelets
- Round/oval in shape
- Visible red/pink granules
- Sensitive to activation
Platelet activation
- Engagement of adhesion molecules; leads to granule release
- eg. ADP, VWF, TXA2 & fibrinogen
- Granules contain ADP and TXA2 (thromboxane)
- This activates platelet in an autocrine way
Von Willebrand Factors (VWF)
- large protein
- under normal conditions; doesn’t bind with platelets
- under intense shear forces, platelet binding sites are exposed
Primary Haemostasis
1) Vascular damage
2) Platelets bind to VWF or Collagen
3) ADP and thromboxane released
4) more platelets activated
5) Negatively charged phospholipid surface promotes thrombin generation
6) Leads to fibrin generation
Nomenclature of coagulation factors
- pro-cofactor is identified by ‘F’ for factor and the
appropriate Roman numeral (eg. factor 8 is FVIII) - cofactor or active enzyme adds a small ‘a’ (eg. FVIII becomes FVIIIa)
- inhibited (non-active) forms acquire a little ‘i’ for inactive (FVIIIai)
The ‘resting’ state
- clotting factors are pre-synthesised in the liver and circulate the blood in their inactive form
- tissue factor; trigger for blood coagulation is a cell surface protein, not in contact with blood normally
- Endothelial cells have anti-coagulant surfaces due to the presence of thrombomodulin, TFPI and antithrombin
Initiation of procoagulant response
Vascular damage results in blood being exposed to cells expressing tissue factor (TF)
Amplification network leads to explosive generation of thrombin which converts fibrinogen (soluble) to fibrin (insoluble)
Thrombin activates platelets and activated platelets accelerate thrombin generation
Fibrin cross-links platelets to form a stable clot
Anticoagulant process
- TFPI is associated with EC surface
- Thrombin stimulates the release of TFPI
- Accelerated by heparin sulfate proteoglycans on the surface of ECs
Two ways to lab assess blood coagulation
- Activated partial thromboplastin time (APTT)
- Prothrombin time (PT)
