seminar22-190527104307.pdf

FROM : HARVEEN BHUSARI .  Introduction  Coagulation mechanism  Coagulation factors  Intrinsic pathway  Extrinsic pathway  Fibrinolytic system  Laboratory test for secondary hemostasis FIBRINOGEN  Level is greatest among coagulation proteins.  Three pairs of polypeptides – Aa,Bb...

FROM : HARVEEN BHUSARI .  Introduction  Coagulation mechanism  Coagulation factors  Intrinsic pathway  Extrinsic pathway  Fibrinolytic system  Laboratory test for secondary hemostasis FIBRINOGEN  Level is greatest among coagulation proteins.  Three pairs of polypeptides – Aa,Bb and gamma – held by disulphide bonds.  Three domains : two outer D domains and one central E domain.  Fibrinopeptides A and B are located in central E domain.  Also an acute phase reactant protein. PROTHROMBIN Converted to thromin by prothrombinase . THROMBOPLASTIN  Required for activation of FvII .  Composed of protein and phospholipid .  Max concentration in brain,placenta and lungs. LABILE FACTOR  Heat labile. Inactivated at room temperature rapidly.  Activated by thrombin  Stored in platelet alpha granules – released from activated platelets.  Prothrombinase complex STABLE FACTOR  Tissue injury – complex between single chain form of factor vII , tissue factor and calcium – generates Xa from X.  Factr Xa then in reverse reaction cleaves FVII to FVIIa .  Also activates FIX ANTIHEMOPHILIC FACTOR  Circulates in plasma as noncoavalently bound complex of two components : FVIIIc and vWf .  FVIII : LMW, has procoagulant activity and is Xlinked .  Gene for it is on long arm X chromosome.  Composed of various domains : A1 -A2 -B -A3 -C1 -C2.  Thrombin cleaves FVIII to form FVIIIa .  This thn acts as a cofactor for FX to FXa . Von willibrand factor  High molecular weight component.  Autosomal inheritance  Synthesised by endothelial cells and megakaryocytes .  Functions : carrier protein for FVIII and also mediates adhesion of plts to subendothelium at sites of vessel damage. CHRISTMAS FACTOR  Vit K Dependent.  Activated by FXIa and FVIIa  Inherited as sex linked manner  Def: Hemophilia B Stuart Prower factor  Vit k dependent  Activated by both intrinsic and extrinsic pathways. Factor XI FACTOR XII  Site of production : Liver  FXII to FXIIa by kalikerin , plasmin and by autoactivation .  Functions : prekalikerin to kalikerin  Converts FXI to FXIa  Activates fibrinolytic and complement systems. FACTOR XIII  It is a transglutaminase  Stablizes fibrin clot. HIGH MOLECULAR WEIGHT KININOGEN  Accelerates activation of FXII and prekalikerin .  It is a source of bradykinin .  Bradykinin : increases vessel permeability, small vessel dilatation, smooth muscles contraction, vasodilation ,antithrombotic and antiplatelet activity. FIBRINOLYTIC SYSTEM  PROCESS OF DISSOLUTION OF BLOOD CLOTS IN ORDER TO MAINTAIN BLOOD IN FLOW STATE.  Major enzyme : plasmin  Plasmin can cleave fibrinogen as well as fibrin.  Plasmin digests insoluble -cross linked fibrin to release FDP which are then cleared by macrophages.  ACTIVATORS : tissue plasminogen activator and kallikerin  INHIBITORS : alpha -2 antiplasmin , alpha -2 macroglobulin , plasminogen activator inhibitors (PAI1 AND PAI 2) , thrombin activated fibrinolytic inhibitor (TAFI). FIBRIN DEGRADATION PRODUCTS NATURAL INHIBITORS OF COAGULATION  ANTITHROMBIN  PROTEIN C  PROTEIN S  TISSUE FACTOR PATHWAY INHIBITOR (TFPI) LABORATORY TEST FOR SECONDARY HEMOSTASIS SPECIMEN COLLECTION  Venepuncture blood  Anticoagulant of choice : 3.2% aq trisodium citrate.  Blood : anticoagulant ratio = 9:1 Automatation in coagulation  Nephelometry  Electromechanical clot detection systems (steel ball)  Chromogenic detection methods  Thromboelastography  Calliberated automated thrombogram  Rotem THANK YOU…!!!