ANTITHROMBIN ACTIVITY/FUNCTIONAL TEST

The antithrombin function test measures how well antithrombin—an endogenous anticoagulant that inhibits thrombin and factor Xa—works. It is a functional assay (chromogenic or clot‑based) reported as percent of normal activity. Low activity suggests congenital or acquired deficiency (increasing venous thrombosis risk) from genetic defects, liver disease, nephrotic syndrome, DIC, or effects of heparin; timing and anticoagulants can alter results.

Antithrombin is a serine protease inhibitor that neutralizes activated coagulation factors—primarily thrombin (IIa) and factor Xa, and to a lesser extent IXa, XIa, and XIIa—by forming irreversible complexes. Its anticoagulant effect is markedly accelerated by heparin and endothelial glycosaminoglycans, helping limit clot propagation and maintain hemostatic balance; deficiency raises the risk of venous thrombosis.

Laboratory evaluation includes a functional antithrombin assay (commonly anti–Factor Xa or thrombin‑based) and an antigen (immunologic) level; comparison distinguishes type I (low activity and antigen) from type II (low activity, normal antigen). Confirmatory SERPINC1 genetic testing can identify pathogenic variants. Testing should ideally be done off heparin/DOAC therapy and away from acute thrombosis or pregnancy; family screening may follow.

Low antithrombin activity means reduced levels or function of a natural blood‑clot inhibitor, raising the risk of abnormal clotting (especially venous thromboembolism). Causes include inherited deficiency or acquired states such as liver disease, nephrotic syndrome, disseminated intravascular coagulation, severe illness or heparin exposure. It can make heparin less effective. Management treats the cause and may include anticoagulation or antithrombin replacement.

Protein C deficiency is diagnosed with blood tests: a protein C activity (functional) assay and a protein C antigen level to distinguish type I vs II deficiency. If indicated, genetic testing of the PROC gene can confirm inherited deficiency. Testing should be delayed until after acute thrombosis and when not on vitamin K antagonists or direct oral anticoagulants, as these can lower levels.

A thrombin function test (thrombin time) measures how quickly added thrombin converts fibrinogen into fibrin, assessing the final step of clot formation. Prolonged time suggests low or dysfunctional fibrinogen or the presence of thrombin inhibitors (heparin, direct thrombin inhibitors). It helps diagnose fibrinogen disorders and guides anticoagulant management; abnormal results lead to further coagulation testing.