Coagulation Cascade Flashcards
Reaction system that begins with FXII and culminates in fibrin polymerization
Intrinsic Pathway
Known as the primary step in coagulation because this factor could be found in blood, whereas TF could not.
Activation of Factor XII
Factors involved in intrinsic pathway
XII, pre-K, HMWK, XI, IX, VIII, X, V, prothrombin (II), and fibrinogen (I)
Complex in the intrinsic pathway that is crucial to the activation of
Factor X
In vivo activation of FXII begins at the activation of
Contact Group
Induces the conversion/activation of HMWK into Bradykinin and FXII
Kallekrein
IN VITRO activation of FXII will begin when
Exposed to negatively charged surface (glass)
FXIIa or PK and HMWK will then activate
FXI to FXIa
This tenase or complex that will activate to FX to FXa in Intrinsic factor
IXa:VIIIa complex with the presence of calcium and phospholipid
All these factors in intrinsic pathway cause bleeding if affected EXCEPT for
Factor XII (no bleeding risk/tendency)
Lab test for Intrinsic pathway
PT, APTT (measure XII, XI, IX, VIII)
Formation of TF:VIIa has since proven to be the primary in vivo initiation mechanism for coagulation
Extrinsic Pathway
T/F: TF is not found on blood (released only if there is injury in the blood vessel)
TRUE
Factors involved in Extrinsic pathway
VII, X, V, prothrombin (II) and fibrinogen (I)
FVIIa will activate FX and FXa with
TF:VIIa (with the presence of calcium and phospolipid)
Where IF and EF meet
Common pathway
Common pathway is composed of what factors?
FX, FV, FII (prothrombin), FI (fibrinogen)
FXa binds with its cofactor FVa in the presence of calcium and phospholipid to form the Xa:Va complex, which will then convert
Prothrombin (FII) to thrombin (FIIa)
Thrombin, in the presence of calcium activates
- Fibrinogen to fibrin polymer (unstabilized)
- FIIa Activates FXIII to FXIIIa (fibrin stabilizing factor)
FXIIIa > Stabilize the unstable fibrin polymer which will result to
Cross-linked fibrin
- Occurs on tissue factor-expressing cells and produces 3% to 5% of the total thrombin generated
- Happens in extrinsic pathway
Initiation phase
Refers to extrinsic tenase complex formation and generation of small amounts of __
FXa, FIXa, and thrombin
1%-2% - normally present in blood in activated form
FVIIa
Provide tissue factor
Fibroblast & other sub-endothelial cells
Cofactor to FVIIa
Tissue Factor
Activates low levels of both FIX and FX
TF:VIIa
- Occurs on the platelets, which produces 95% or more of the total thrombin
- Happens in intrinsic pathway
Propagation Phase
Activated by thrombin in the initiation phase bind to platelet membranes and become receptors for FXa and FIXa
Cofactors FVa and FVIIa
Generated in the initiation phase binds to FVIIIa on the platelet membrane to form the intrinsic tenase complex IXa:VIIIa
FIXa
Activates prothrombin and generates a burst of thrombin
FXa binds to FVa to form the prothrombinase complex
- Cleaves fibrinogen into a fibrin clot
- Activates factor XIII to stabilize the clot
- Binds to thrombomodulin to activate the protein C control pathway
- Activates TAFI to inhibit fibrinolysis
Thrombin (FIIa)
- Cleaves fibrinogen into a fibrin clot
- Activates factor XIII to stabilize the clot
- Binds to thrombomodulin to activate the protein C control pathway
- Activates TAFI to inhibit fibrinolysis
Thrombin (FIIa)
