Anti clotting Mechanisms Dr Mahvash Khan MBBS MPhil

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) ◦ 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 III Action of Fibrin & Antithrombin ◦ Most important anticoagulants are those that remove thrombin �Fibrin fibers-formed during the process of clotting �Antithrombin lll �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, 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 1. Hemophilia A Or Classic hemophilia: because of abnormality or deficiency of factor VIII(1/1000 male in USA suffering from disease). 2. Hemophilia B Or Christmas disease: because of deficiency of factor IX.

Thrombocytopenia v v Ø Ø Ø 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-negative sepsis (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 1. 2. 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 1 st hour of heart attack or after the thromboembolic occlusion of coronary artery the heart saved from serious damage.

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