COAGULATION CASCADE

intrinsic pathway

• activated in vitro by contact of coagulation proteins with sub-endothelial tissue

factor 12 to factor 12a

• absorption of factor 12 with negatively charged surface

• prekallikrein-hmwk is absorbed in vivo to the negatively charged surface factor 12

• kallikrein accelerates conversion rate to factor 12a

factor 11 to factor 11a

• calcium acts as a cofactor which is required so that factor 11 cleaves to 11a

• also activated plasminogen

factor 9 to factor 9a

• completes contact activation phase of coagulation

• can also be activated by kallikrein

• factor 9a combines with 8a and calcium platelet phospholipid to activate factor 10 (common pathway)

extrinsic pathway

• in vivo, initiated with the release of tissue factor (factor 3)

tissue factor (f3)

• present in sub-endothelial surface and activated monocytes

• released from the cell membranes into plasma when there is vascular injury

factor 7 to factor 7a

• phospholipid portion of tissue factor activates 7 to 7a

• the 7a and calcium complex on platelet phospholipid converts factor 10 to 10a (common pathway)

common pathway

• the 2 pathways have in common factor 10, factor 5, prothrombin, and fibrinogen

factor 10 to factor 10a

• extrinsic activation occurs when 7a + 3 + calcium on the phospholipid surface is formed and converts 10 to 10a

• intrinsic activation occurs when 8a + 9a + calcium binds with the phospholipid on the platelet surface which in turn activates 10 to 10a

formation of prothrombinase complex

• 10a + 5a + calcium + PL

• this complex converts prothrombin to thrombin

• the reaction is completed once fibrinogen is converted to fibrin to and is stabilized into clot