Normally within the blood coagulation factors circulate in their inactivated state. The endothelium lining blood vessel walls does not contain thrombogenic tissue factor or collagen either meaning normally the coagulation cascade is inactive. However when the vessle wall is lesioned and the subendothelium exposed so are the thrombogenic factors and the cascade initiates via two complexes.
1. Intrinsic Tenase Complex
7a serine protease cleaves 11 and Pk > Activated and anchored to plasma membrane > 11a cleaves subprotein K > 11a diffuses into blood activates 9a > 9a forms complex with 8a > Ca binds on PL and activates 10a
2. Extrinsic Tenase Complex
Outisde components + TF > 7 forms complex with TF > Autoactivation 7 - 7a > Ca kick starts reaction to recruit 10a
Both the intrinsic and extrinsic merge into the common pathway after this and this occurs on the prothrombinase enzyme complex. The key activation factor of this complex is 10a.
10a activated on the PL rich surface of platelets > In presence of Ca activated 10a forms complex with cofactor 5a > Converting prothrombin - thrombin > thrombin dissociates > fibrinogen - fibrin polymer > thrombin recruits platelets to seal breach in vessel wall
DIC (trauma, burn, sepsis, tumour, toxin, ABO incompatibility)
Systemic activation of cascade > widespread deposition of fibrin > clotting and use of platelets > ischemia due to restriction to blood flow > organ failure
Prolonged PT and APPT, low fibrinogen, Increased D-dimers, fragmented RBC