Clotting cascade - Haemostasis - BB Flashcards
First line of defence against bleeding
Vasoconstriction
In response to endothelial damage - release of endothelins
Endothelins - potent vasoconstrictors/ proteins
What is the most common mechanism of action for coagulation factors
when activated - become serine proteases
Factor X activation
Xa converts
– prothrombin (II) –> Thrombin (IIa)
Trombin (IIa) converts
– Fibrinogen (I) –> Fibrin (Ia)
Tissue factor also known as
thromboplastin
Where is tissue factor expressed?
In sub-endothelial cells (not expressed in endothelial cells)
- therefore no sig exposure to circulating blood
Exposed by endothelial damage
Tissue factor activates which pathway of clotting cascade?
Extrinsic pathway
Interacts with VII to make VIIa
TF:VIIa cofactor - activates factor X
Thrombin causes activation and positive feedback via which clotting factors?
Va (5)
VIIIa (8)
XIa (11)
IXa:VIIIa (9:8 cofactor)
All feedback and activate factor X->Xa
Haemophelia is caused by low levels of which clotting factors?
IXa (9) or VIIIa (8)
Which clotting factor is produced in endothelial cells?
Factor VIII (8)
Multicomponent complexes are what 3 components bound together
and what do they need?
- Active clotting factor functioning as an enzyme
- Co-factor
- Substrate
Requires:
- phospholipid (either from TF bearing cells or platelets)
- calcium (Co-factor)
Substrate is always factor X (–>Xa)
Extrinsic Xase
TF:VIIa
Phospholipid of TF-bearing cells
Enzyme: Factor VIIa
Co-factor: tissue factor (TF)
Substrate: factor X (converting into Xa)
Intrinsic Xase
IXa:VIIIa
Phospholipid: from platelets
Enzyme: factor IXa (9)
Cofactor: Factor VIIIa
Substrate: Factor X
Calcium’s role in clotting cascade:
Required for clot formation
Used to be called factor IV
Stored by platelets - released on activation
NOTE: EDTA in blood-sample-tubes binds to calcium and prevents clotting
Factor XIII (13)
And how is it activated
Crosslinks fibrin - stabilising the fibrin plug
Requires calcium as a co-factor
Activated by thrombin (IIa) formation
Factor XII (12) role:
Can activate factor XI->XIa (11) — Thrombin also does this conversion
Activated contact with negatively charged substance such as silica
Basis for Partial Thromboplastin Time (PTT)
First in the intrinsic pathway
Full coagulation cascade: