Description
In order to stop local bleeding, thrombin, a natural thrombin drug that catalyzes
the transformation of fibrinogen to fibrin, is frequently used. Thrombin is synthesized
from cow plasma, and it is used to stop bleeding from open vessels when it
is not possible to use other methods. It is used to stop light bleeding.
Uses
Thrombostat (Parke-Davis).
General Description
Thrombin is a sterile protein substanceprepared from prothrombin of bovine origin. It is used as atopical hemostatic because it can clot blood, plasma, or a solutionof fibrinogen without addition of other substances.Thrombin also may initiate clotting when combined withgelatin sponge or fibrin foam.
For external use it is applied topically to the wound, as asolution containing 100 to 2,000 National Institutes ofHealth (NIH) units/mL in sodium chloride irrigation or sterilewater for injection or as a dry powder.
Biochem/physiol Actions
The main function of thrombin is the cleavage of fibrinogen to fibrin, to assist stable clot formation. A wide range of mutations in the prothrombin gene contributes to its deficiency resulting in coagulation disorders like dysprothrombinemia and hypoprothrombinemia. High levels of thrombin elicit neurotoxicity in dopaminergic neurons and contributes to the progression of Parkinson′s disease. Altered thrombin levels modulates the coagulation pathway in multiple sclerosis. Patients with coronary artery disease (CAD) show elevated levels of thrombin. Thrombin accumulation in neurofibrillary tangles of the brain may contribute to the aggregation of tau protein and pathophysiology of Alzheimer disease.
Purification Methods
Thrombin is purified by chromatography on a DEAE-cellulose column, while eluting with 0.1M NaCl, pH 7.0, followed by chromatography on Sephadex G-200. The final preparation is free from plasminogen and plasmin. [Yin & Wessler J Biol Chem 243 112 1968.] Thrombin from bovine blood is also purified by chromatography using p-chlorobenzylamino--aminocaproyl agarose, and gel filtration through Sephadex G-25. [Thompson & Davie Biochim Biophys Acta 250 210 1971.] Thrombin from various species was purified initially by precipitation of impurities with rivanol. [Miller Nature 184 450 1959.] Tissue inhibitor of metalloproteins (TIMP, from human blood plasma), Mr ~30,000. These are purified by an [anti-human amniotic fluid-TIMP]-Sepharose immuno-affinity column and eluted with 50mM glycine/HCl pH 3.0 buffer that is 0.5M in NaCl, and followed by gel filtration [Cawston et al. Biochem J 238 677 1986].
