There are three major natural coagulation inhibitor pathways:
1. Protein C and S
- Thrombin, in addition to being a component of the coagulation cascade to form a fibrin clot, also activates protein C. Once protein C is activated, it exerts an anticoagulant effect in the blood via inhibition of factors V and VIII. Protein S functions to enhance this inhibition.
- Deficient or defective protein C or S results in hypercoagulability (eg, deep vein thrombosis). Protein C and S assays can be performed if a clinician suspects that a hypercoagulable state secondary to protein C or S deficiency is present.
- Factor V Leiden is a genetic condition in which factor V is resistant to the actions of protein C, resulting in a hypercoagulable state. Genetic testing can be ordered to assess for this condition.
2. Tissue factor pathway inhibitor (TFPI)
- Recall that tissue factor (factor III) activates the extrinsic pathway of the coagulation cascade. TFPI acts to inhibit the activation of the extrinsic pathway. The role of TFPI in many diseases is being studied. Routine laboratory evaluation of TFPI does not exist.
3. Antithrombin III (AT-III)
- Antithrombin III inhibits thrombin (factor IIa) and other factors. AT-III will be discussed in more detail with the drug heparin.