Initiation
Vessel injury exposes bare collagen and tissue factor.
FVII \(\stackrel{\text{Tissue factor}}{\to}\) FVIIa
FX \(\stackrel{\text{FVIIa}}{\to}\) FXa
Meanwhile, platelets undergo
- Adhesion to the denuded collagen via vWF
- Aggregation by binding to each other via GPIIb/IIIa-fibrinogen complex
- Activation, which releases
- Serotonin \(\to\) vasoconstriction
- Thromboxane and ADP \(\to\) activate more platelets
- Lots of FV
Vasoconstriction + platelet plug formation produces primary haemostasis
$$FV \xrightarrow{\text{FXa (slow)}} FV_a$$
$$\text{Prothrombin} \xrightarrow{\text{FXa+FVa+activated plt membrane+iCa}} \text{Thrombin}$$
Amplification
Thrombin...
- Activates more platelets
- Activates FV (from platelet granules)
- Activates FXI, which activates FIX
- Cleaves vWF off factor VIII and activates it; FIX+FVIII activates more FX
- FXa + FVa + plt membrane + iCa \(\to\) more thrombin \(\to\) positive feedback
Propagation
$$\text{Fibrinogen} \xrightarrow{\text{Thrombin}} {\text{Fibrin}}$$
$$\text{FXIII} \xrightarrow{\text{Thrombin}} {XIIIa} \to \text{Crosslinks fibrin strands}$$
Negative feedback
Protein C \(\xrightarrow{\text{thrombin}}\) Protein Ca (with protein S) \(\to\) inactivates thrombin, indirectly initiates thrombolysis
Antithrombin III: circulating serine protease inhibitor that inactivates thrombin, FXa, FIXa, FXIa. Potentiated by heparin.
Intact endothelium express anticoagulants that prevent clot propogation out of area of injury
- Tissue factor pathway inhibitor (TFPI) \(\to\) inhibits TF-VIIa complex
- Thrombomodulin \(\to \ \uparrow\)activation of protein C by thrombin