Normal homeostasis depends on a balance between procoagulant and anticoagulant systems. The coagulation cascade leads to formation of fibrin: soluble fibrinogen is converted into insoluble fibrin, which stabilizes the clot.
Coagulation can be initiated through the extrinsic or intrinsic pathways.
The extrinsic pathway is activated by tissue factor (TF). TF is exposed when endothelial injury occurs, and it activates factor VII to initiate the extrinsic pathway. Increased TF expression occurs in sepsis, malignancies, ruptured atheromatous plaques, and other conditions.
The intrinsic (contact) pathway is initiated by activation of factor XII in the presence of high-molecular-weight kininogen (HMWK) and plasma prekallikrein (PK). The intrinsic pathway does not contribute significantly to hemostasis in vivo. However, ex vivo activation of the contact pathway occurs during hemodialysis, cardiopulmonary bypass, and extracorporeal membrane oxygenation (ECMO), where blood comes into contact with artificial surfaces such as glass.
Both pathways can be activated in pathological conditions such as infections. Before a fibrin clot forms, a platelet plug forms and temporarily stops bleeding.
Normally occurring antithrombogenic factors include plasminogen, tissue plasminogen activator (tPA), proteins C and S, thrombomodulin, and antithrombin.
Plasmin, derived from plasminogen, dissolves the fibrin clot into fibrin degradation products (FDPs). tPA is released from endothelial tissues and catalyzes the conversion of plasminogen to plasmin. Release of tPA is stimulated by tissue occlusion, thrombin, epinephrine, vasopressin, and strenuous exercise.
D-dimers are produced by digestion of cross-linked fibrin and are specific indicators of fibrinolysis. D-dimers will be positive in DIC and deep vein thrombosis.
Several inhibitors regulate fibrinolysis:
Factors II, VII, IX, X and protein C and S are vitamin K dependent factors. Protein C inactivates factors V and VIII, while protein S acts as a cofactor for protein C.
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