Hemostasis Hemostasis depends on the integrity of Blood vessels Platelets Coagulation factors

STEPS IN HEMOSTASIS Transient arteriolar vasoconstriction due to reflex neurogenic mechanism and secretion of endothelin. Formation of primary platelet plug due to adhesion of platelets to collagen and traces of thrombin. Conversion into permanent plug supported by fibrin clot formed by activation of the coagulation cascade. Lysis of fibrin and confinement of clot to the site of injury.

Intrinsic Pathway XII XIIa Extrinsic Pathway XI XIa VIIa TF VII IX IXa HMWK Prekallikerin Surface XII XIIa Extrinsic Pathway XI XIa VIIa TF VII IX IXa VIIIa X Xa Va Prothrombin Thrombin Fibrinogen Fibrin XIIIa Cross linked fibrin

Prothrombin Time XIIa XII XI XIa VIIa TF VII XI IXa VIIIa X Xa Va HMWK Prekallikerin Surface XIIa XII XI XIa VIIa TF VII XI IXa VIIIa X Xa Va Prothrombin Thrombin Fibrinogen Fibrin XIIIa Cross linked fibrin

Partial Thromboplastin Time HMWK Prekallikerin Surface XIIa XII XI XIa VIIa TF VII XI IXa VIIIa X Xa Va Prothrombin Thrombin Fibrinogen Fibrin XIIIa Cross linked fibrin

Antithrombin III AT III XIIa XII XI XIa VIIa TF VII XI IXa VIIIa X Xa HMWK Prekallikerin Surface XIIa XII XI XIa VIIa TF VII XI IXa VIIIa X Xa Va Prothrombin Thrombin AT III Fibrinogen Fibrin XIIIa Cross linked fibrin

Protein C Protein C XIIa XII VIIa TF VII XI XIa XI VIIIa X Xa Va HMWK Prekallikerin Surface Protein C XIIa XII VIIa TF VII XI XIa XI IXa VIIIa X Xa Va Prothrombin Thrombin Fibrinogen Fibrin XIIIa Cross linked fibrin

ANTITHROMBOTIC FUNCTION OF NORMAL ENDOTHELIUM Separation of blood from subendothelium that activates platelets and initiates blood coagulation Release of PGI2 that diminishes platelet response to activating stimuli Binding sites for anticoagulants Thrombomodulin binds thrombin altering its enzymatic activity with activation of protein C. Antithrombin III binding sites

PROTHROMBOTIC ROLE OF ENDOTHELIUM Production of von Willebrand factor. Synthesis of TF (induced by TNF, IL-1). Binding of IXa and Xa on their surfaces.

Dual Role of Endothelium Production of VWF Synthesis of TF Binding of IXa and Xa Separation of blood from subendothelium Release of PGI2 Binding sites for: Thrombomodulin Antithrombin III INHIBITION OF CLOTTING INDUCTION OF CLOTTING

Virchow’s Triad Thrombosis Endothelial Injury Hypercoagulability Abnormal Bl. Flow Hypercoagulability

Endothelial injury Important in heart and arterial thrombosis Caused by Hemodynamic stresses Homocystinuria and hypercholesterolemia Cigarette smoking Inflammatory conditions Results in Platelet interaction with subendothelial collagen Release of tissue factor

Alteration in Blood Flow Turbulence in heart and arteries lead to endothelial injury Stasis is the major cause of venous thrombosis Stasis and turbulence lead to Disruption of laminar flow causing platelets endothelial contact Prevent dilution of activated factors Decrease inflow of coagulation factor inhibitors Help activate endothelial cells leading to thrombosis and leukocyte adhesion

Hypercoagulability Genetic Causes Acquired Causes Factor V mutation Antithrombin III deficiency Protein C deficiency Protein S deficiency Defects in fibrinolysis Acquired Causes Bed rest and immobilization Myocardial infarction Tissue damage (surgery, accidents, burns) Cancer Artificial valves Antiphospholippid syndrome Polycythemia Sickle cell disease Oral contraceptives and hyperestrogenemia

Arterial thrombi Endothelial damage Against bl. flow Prominent Gray Yes Heart; coronary, cerebral, aorta Venous thrombi Stasis With bl. blow Less prominent Red Yes Lower limb veins Etiology Growth Lines of Zahn Color Occlusive Location