BLOOD-CLOTTING-2_38076

BLOOD-CLOTTING-2_38076 - Overview of Pathways of Blood...

Info iconThis preview shows pages 1–9. Sign up to view the full content.

View Full Document Right Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
This is the end of the preview. Sign up to access the rest of the document.

Unformatted text preview: Overview of Pathways of Blood Coagulation Vitamin K dependent factor I. REGULATION OF CLOTTING To avoid coagulation from becoming more generalized or to prevent unwanted bleeding, anti- coagulation mechanisms are necessary. It is especially vital to regulate circulating thrombin levels. One method is via feedback mechanisms in the coagulation cascade that regulate balance between inactive proenzymes and active enzymes that ultimately lead to conversion of inactive prothrombin to thrombin. Thrombin activation is also regulated by specific thrombin inhibitors. The most important is antithrombin III , a serine protease inhibitor (serpin), which can also inhibit activities of factors IXa, Xa, XIa and XIIa. II. REGULATION OF CLOTTING Heparin , a sulfated polysaccharide (termed a glycosaminoglycan), is found on the surface of endothelial cells. It is released in response to injury and binds to a site on antithrombin III, altering the protein conformation, which increases the affinity of the inhibitor for thrombin. This controls the initiation of the intrinsic cascade and is the basis for clinical use of heparin as an anti-coagulation agent. Another protein, the tissue factor pathway inhibitor (TFPI) inhibits the extrinsic pathway. III. REGULATION OF CLOTTING Thrombomodulin is another endothelial cell-surface protein that binds thrombin. As a result, thrombin acquires a capacity (>1000 fold increase) to activate protein C by proteolysis. Activated protein C interacts with a co-factor, protein S , to become a potent anti-coagulant by inactivating factors VIIIa and Va by proteolysis. I. Anti-clotting Factors Inhibitors of clot Formation (anti-coagulants): Antithrombin III. Protein produced by the liver & inhibits the activities of IXa, Xa, XIa, XIIa and thrombin . Activated by heparin. Heparin, Sulfated polysaccharide synthesized by mast cells. Activates antithrombin III by conformational change. Used therapeutically as rapid and potent inhibitor of coagulation. Thrombomodulin. Glycoprotein on the surface of endothelial cells. Combines with thrombin to proteolytically activate protein C. Protein C . Gla-containing serine protease that degrades factors Va and VIIIa. Requires protein S for stabilization. Protein S. Cofactor that stabilizes activated protein C. Tissue Factor pathway inhibitor (TFPI). Inhibits factor VIIa from activating factors IX and X, limiting duration of the extrinsic pathway. Fig. 1 - Inhibition of Clot Formation Clot "busting Plasminogenesis COOH S S Arg Val COOH S S Arg Val plasminogen t-PA (endothelium) plasmin NH 2 NH 2 (kidney) urokinase (exogenous) streptokinase Fibrin clot Fibrin fragments !...
View Full Document

This note was uploaded on 01/23/2011 for the course BCHS 4361 taught by Professor Echberg during the Spring '09 term at University of Houston.

Page1 / 32

BLOOD-CLOTTING-2_38076 - Overview of Pathways of Blood...

This preview shows document pages 1 - 9. Sign up to view the full document.

View Full Document Right Arrow Icon
Ask a homework question - tutors are online