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Anti clotting Mechanisms. Dr Mahvash Khan MBBS, MPhil. Lysis of Blood Clot. Occurs inside the blood vessels, it is also called fibrinolysis Occurs due to a substance known as plasmin ( fibrinolysin ) Plasmin is formed from plasminogen ( profibrinolysin )
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Anti clotting Mechanisms DrMahvash Khan MBBS, MPhil
Lysis of Blood Clot • Occurs inside the blood vessels, it is also called fibrinolysis • Occurs due to a substance known as plasmin (fibrinolysin) • Plasmin is formed from plasminogen (profibrinolysin) • Plasmin is a proteolytic digestive enzyme • Plasmin digests fibrin fibers, Factor V, factor Vlll, prothrombin, factor Xll
Significance of the lysis • Reopening of the affected vessels • Prevents development of infarction
Prevention of blood clotting under normal conditions • Intravascular anti coagulants • Flow of blood • Endothelial surface factors • Smoothness of endothelial cell surface Prevents contact activation of the intrinsic clotting system • Layer of glycocalyx Muccopolysaccharide adsorbed to the vascular surfaces repels clotting factors and platelets
Prevention of blood clotting under normal conditions • Thrombomodulin • Protein bound to endothelial membrane • Binds thrombin • Thrombomodulin –thrombin complex also activates a plasma protein complex known as protein C • Acts as anticoagulant by inactivating activated factors V & VII
Prevention of blood clotting under normal conditions • Antithrombin Action of Fibrin & Antithrombin III • Most important anticoagulants are those that remove thrombin • Fibrin fibers-formed during the process of clotting • Antithrombinlll • Antithrombin-heparin cofactor • Thrombin formed from prothrombin gets adsorbed to the fibrin fibers • Helps prevent spread of thrombin into the remaining blood
Heparin • Powerful anticoagulant which is a negatively charged polysaccharide • Used widely as a pharmacological agent • Under physiological condition its concentration is low • When it combines with antithrombin III the effectiveness of antithrombin III increases • The complex removes other activated coagulation factors----XII,XI,X & IX
Conditions causing Excessive bleeding • Vitamin K deficiency • Hemophilia • Thrombocytopenia
Vitamin K • Fat soluble vitamin • Required for synthesis of clotting factors • Action • Acts as a cofactor at a late stage in the synthesis by liver of coagulation proteins • Prothrombin, VII, IX& X • Causes gamma carboxylation of glutamate residues in the synthesis of clotting factors
Vitamin K • Continually synthesized in GIT • Deficiency seldom occurs • Deficiency can occur because of the failure of the liver to secrete bile
HEMOPHILIA Hemophilia is a bleeding (hemorrhagic) disease occurs almost exclusively in males. Types • Hemophilia A Or Classic hemophilia:because of abnormality or deficiency of factor VIII(1/1000 male in USA suffering from disease). • Hemophilia B Or Christmas disease:because of deficiency of factor IX.
Thrombocytopenia • Very low quantity of platelets in circulating blood is called Thrombocytopenia. • Bleeding occurs in small venules & capillaries so the hemorrhage occurs through out all body tissues. • Platelets normal, 150,000-300,000 • Bleeding occurs in < 50,000/ µl • Lethal count < 10,000/ µl
Disseminated intravascular coagulation • A pathological process in the body where the blood starts to coagulate throughout the whole body. This depletes the body of its platelets and coagulation factors, and there is a paradoxically increased risk of hemorrhage. It occurs in critically ill patients, especially those with Gram-negativesepsis (particularly meningococcal sepsis) and acute promyelocytic leukemia
Thromboemboli • Thrombi: An abnormal clot that develops in blood vessel • Emboli: freely flowing clot is known as emboli Continuous flow of blood passes the clot away from its attachment & causes the clot to flow with the blood . • Emboli originating from large arteries & left side of heart can flow to periphery & plug arteries or arterioles in brain, kidney or else where. • Emboli originating from venous system or right side of heart generally flow into the lungs to cause pulmonary embolism.
Causes of thromboembolic conditions • Roughened endothelial surface of vessels: This is because of arteriosclerosis, infections or trauma, these factors initiating coagulation • Slow flowing of blood
Use of t-PA in treating intravascular clot: Tissue plasminogen activator when delivered directly to a thrombosed area through a catheter it activates plasminogen to plasmin & dissolve i/v clot. Uses: In 1st hour of heart attack or after the thromboembolic occlusion of coronary artery the heart saved from serious damage.
