Antithrombin

Fibrin and control · Serpin Heparin cofactor

A serpin made in the liver that irreversibly traps the active site of thrombin and factor Xa, and to a lesser degree factors IXa, XIa and XIIa. Endothelial heparan sulfate accelerates it physiologically; pharmacological heparin does the same thing more than a thousand-fold, and that is the entire mechanism of heparin.

Traced from the start

  1. Tissue factor and the extrinsic triggerVitamin K cycle and gamma-carboxylation
  2. Contact activation system (factor XII, prekallikrein, high-molecular-weight kininogen)
  3. Subendothelial collagen and von Willebrand factor
  4. Tissue factor-factor VIIa complex (extrinsic tenase)Factor IXaFactor VIIIa and its von Willebrand factor carrierActivated platelet phospholipid surface
  5. Factor XaFactor VaProthrombin (factor II)
  6. Thrombin (factor IIa)
  7. Antithrombin

Detail

Inhibits
Thrombin and factor Xa principally, and also factors IXa, XIa and XIIa
Accelerated by
Endothelial heparan sulfate; heparin, LMWH and fondaparinux by more than 1000-fold
Formerly called
Antithrombin III
Depleted in
Nephrotic syndrome (urinary loss), hepatic failure (reduced synthesis), DIC (consumption), and asparaginase therapy

When it goes wrong

Inherited antithrombin deficiency, autosomal dominant and the most thrombogenic of the common inherited thrombophilias

Venous thromboembolism from young adulthood, and apparent heparin resistance — the APTT fails to prolong despite escalating heparin doses; give antithrombin concentrate or switch to a direct thrombin inhibitor

Antithrombin lost in the urine in nephrotic syndrome

Hypercoagulable state with a characteristic predilection for renal vein thrombosis

Practise this structure

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