SECONDARY HEMOSTASIS DIANA RYSA S. ASUNCION, RMT COLLEGE OF MEDICAL LABORATORY SCIENCES
SECONDARY HEMOSTASIS SECONDARY HEMOSTASIS Composed of coagulation factors and platelet phospholipids Divided into three pathways: Extrinsic Pathway Intrinsic Pathway Common Pathway
SECONDARY HEMOSTASIS COAGULATION FACTORS Also known as pro-coagulants Circulate in inactive forms EXCEPT factors III and IV (normally active) Synthesized in the liver EXCEPT factors III, IV and VIII:C FUNCTIONS Enzymatic: Zymogens, Serine Protease Substrate Co-factor: Factor III, V, VIII and HMWK
SECONDARY HEMOSTASIS NUMERAL NAME SYNONYMS I Fibrinogen II Prothrombin Prethrombin III Tissue Factor Tissue thromboplastin IV Calcium V Proaccelerin Labile factor accelerator globulin (aCg) VII Proconvertin Stable factor Serum prothrombin conversion accelerator (SPCA) Autoprothrombin I VIII:C Anti- hemophilic factor (AHF) Anti-hemophilic globulin (AHG) Anti-hemophilic factor A Platelet cofactor 1
SECONDARY HEMOSTASIS NUMERAL NAME SYNONYMS IX Plasma thromboplastin component (PTC) Christmas factor Anti- hemophilic factor B Platelet cofactor 2 X Stuart-Prower factor Stuart factor Prower factor Autoprothrombin III XI Plasma thromboplastin antecedent Anti-hemophilic factor C XII Hageman factor Glass factor Contact factor XIII Fibrin stabilizing factor Laki-Lorand factor Fibrinase Fibrinoligase Plasma transglutaminase Prekallikrein Fletcher factor High molecular weight kininogen Fitzgerald factor Williams factor Flaujeac factor Contact activation cofactor
SECONDARY HEMOSTASIS NUMERAL NAME SYNONYMS Prekallikrein Fletcher factor High molecular weight kininogen Fitzgerald factor Williams factor Flaujeac factor Contact activation cofactor
SECONDARY HEMOSTASIS COAGULATION FACTORS PHYSICAL PROPERTIES Contact Group Intrinsic accessory pathway Contact phase group Factors that can be absorbed by a contact with a negative charged surface: Glass Collagen Sub-endothelium layer
SECONDARY HEMOSTASIS COAGULATION FACTORS PHYSICAL PROPERTIES Prothrombin Group Factors: FII, FVII, FIX, FX Proteins: Protein C, S and Z Calcium and vitamin K dependent ( B. fragilis , E. coli) Gamma carboxylation of glutamic acid at the N terminal end allows the factors to bin calcium and platelet phospholipids (calcium bridges) Inhibited by oral anticoagulants Comadin Warfarin
SECONDARY HEMOSTASIS COAGULATION FACTORS PHYSICAL PROPERTIES Fibrinogen Group Fibrinogen: most concentrated coagulation factor Calcium dependent Consumed during coagulation Seen only in PLASMA Only factors found in the alpha granules of platelets
SECONDARY HEMOSTASIS PATHWAYS EXTRINSIC PATHWAY Factors: VII, III, Calcium Factors are not found in plasma FVIIa : single chained factor Extrinsic Tenase Complex: FVIIa+Calcium+FIIIa Complex It can alternatively activate FIX
SECONDARY HEMOSTASIS PATHWAYS INSTRINSIC PATHWAY Factors: FXII, XI, IX, VIII, HMWK, PK, Ca ++ All components are found in plasma Exposure to negative charge surface Glass Collagen during tissue damage Intrinsic Tenase Complex: FIX+FVIII+Ca ++ +Phospholipids It can activate extrinsic pathway which produces two chained FVII via FXII FIX+Kalikrein
SECONDARY HEMOSTASIS PATHWAYS INSTRINSIC PATHWAY Another is FX can hydrolyze FVII into two chain (85x pro-coagulant activity) KALIKREIN Kinin system Involves in the chemotaxis and the sensation of pain, mediate inflame response, increase vascular permeability, vasodilation Prekalilreinn , Kalikrein , HMWK and Bradykirin Fibrinolysis and Complement Produces plasmin Plasmin: activates C1 and cleaves C3 Directs activations of FIX Activation of FXII
SECONDARY HEMOSTASIS PATHWAYS COMMON PATHWAY Factors: FX, V, II, I, XIII Involves extrinsic and intrinsic pathway Thrombin converts Fibrinogen to Fibrin Stabilization of fibrin polymer Prothrombinase Complex: FX+V+Ca ++ +Phospholipids
SECONDARY HEMOSTASIS THROMBIN ACTIVATOR Low levels: activates FV and FVIII Activates FXII with calcium Induces platelet aggregation INHIBITOR High levels: inhibits FV and FVII Initiates fibrinolysis by converting plasminogen and plasmin Activates protein C
SECONDARY HEMOSTASIS INHIBITORS OF COAGULATION Anti-thrombin III Inhibits thrombin: XII, XI, X, IX Major inhibitor of thrombin Enhanced by heparin and heparin sulfate Complex enhanced function of ATIII by 2,000-10,000 times Alpha 2 macroglobulin Inhibits thrombin and kallikrein Alpha 1 antitrypsin Inhibits XI and thrombin C1 esterase inhibitor Inhibits FXII, FXI, kalikrein
SECONDARY HEMOSTASIS INHIBITORS OF COAGULATION Protein C-S Inhibits FV and FVIII Vitamin K dependent Alpha 2 antiplasmin Inhibits FXI, FII, FX Primary inhibitor of plasmin LACI Lipoprotein associated coagulation inhibitors
SECONDARY HEMOSTASIS INHIBITORS OF COAGULATION OTHER INHIBITORS Thrombin Activatable FIbrinolysis Inhibitor (TAFI) Plasma procarboxypeptidase Activated TAFI acts as anti- fibrinolytic enzyme inhibiting fibrinolysis Plasminogen Activator Inhibitor (PAI-1) Principal inhibitor of plasminogen activation by inactivating TPA and UPA Single chain glycoprotein