Coagulation Cascade and anticoagulants medications:
• The coagulation cascade or secondary homeostasis is a series of
steps in response to bleedings caused by tissue injury, where each
step activates the next and ultimately produces a blood clot
- There are 2 models to explain the coagulation cascade: the
classical model which include two pathways; the extrinsic and
intrinsic pathway and the cell-based model where there are 3
processes; initiation, amplification and propagation
The cell based model for the coagulation cascade include stages:
• Initiation Phase: injury of vessel wall leads to contact between
blood and subendothelial cells. Tissue Factor (TF) is exposed and
binds to Factor VII which is converted to Factor VIIa. A complex
forms between Tissue Factor and FVIIa activates Factor IX and X.
The Factor Xa binds to Factor Va on the cell surface
• Amplification: The Factor Xa/Va complex converts small amounts
of prothrombin into thrombin. The small amount of thrombin
activates Factor VIII, Factor V, Factor XI and platelets. Factor XIa
converts Factor IX into Factor IXa. Activated platelets bind to
Factor Va, Factor VIIIa and Factor IXa
• Propagation: The Factor VIIa/IXa complex activates Factor X on
the surface of activated platelets. Factor Xa in association with
Factor Va converts large amounts of prothrombin into thrombin
creating a ‘thrombin burst’. The ‘thrombin burst’ leads to the
formation of a stable fibrin clot
, The Classical model for haemostasis involves 3 different pathways:
extrinsic, intrinsic and common pathway.
• The Extrinsic pathway begins when there is injury to the endothelial
tissue, exposing tissue factor to the blood. Tissue factor then
becomes bound with calcium and Factor VIIa to activate Factor X
to Factor Xa
• The intrinsic pathway begins when Factor XII or the Hageman
factor is exposed to collagen, kallikrein and high molecular weight
kininogen and is activated to Factor XIIa.
- Factor XIIa then activates Factor XI into Factor XIa. With a calcium
ion, Factor XIa activates Factor IX into Factor IXa. Then Factor IXa,
Factor VIIIa and calcium form a complex to activate Factor X into
Factor Xa
• The common pathway begins when Factor Xa, Factor Va and
calcium bind together forming a prothrombinase complex. The
prothrombinase complex then activates prothrombin (Factor II)
into thrombin (Factor IIa)
- Then, thrombin converts Factor XIII (known as the stabilising factor)
into XIIIa. Factor XIIIa binds with calcium to then create fibrin
crosslinks to stabilise the clot
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