Abstract
Any agent which inactivates or removes from blood, calcium, prothrombin, or thrombin is an anticoagulant. Theoretically, anti-fibrinogen and antithromboplastin are also possible but have never been convincingly demonstrated. The removal of calcium by oxalates, citrates, or fluorides is well known. As a type of antipro-thrombin, aluminum hydroxide is an excellent example. On mixing and incubating oxalated plasma (0.5 cc.) with aluminum hydroxide cream (0.05 cc.) a plasma is obtained which after the removal of the aluminium hydroxide, will not clot on recalcification, whereas the untreated plasma clots in 2 minutes when calcium is added. The loss of clotting power is not due to removal of thromboplastin, for on adding an active preparation made from rabbit's brain, the normal clotting time is not restored. Furthermore, fibrinogen is not removed, for thrombin (fresh serum) will cause clotting in 10 seconds. Prothrombin must be the constituent that is removed or inactivated by aluminum hydroxide. Significantly, this reagent does not remove or inactivate thrombin.
Hirudin is a type of true antithrombin. Heparin likewise appears to be an antithrombin as the following experiment demonstrates:
Heparin is not neutralized by thromboplastin. Even when excess thromboplastin is present, the clotting time is prolonged as the concentration of heparin is increased. Plasma containing 0.2 mg. of heparin per cc. will not clot, irrespective of the excess of thromboplastin.
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