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Fisiologis hemostasis dan fibrinolisis merupakan dua hal yang berbeda.
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FISIOLOGI HEMOSTASISdan FIBRINOLISISdr. Arthur E. Mongan, M.Sc., Sp.PKSEMESTER-3 BLOK-2 MODUL-3Gangguan Hemostasis: Diagnosis LaboratoriumFK UNSRAT MANADO2010
PERIPHERAL BLOODPLASMA and (blood) CELLS
THE HEMATOPOIETIC SYSTEMThe (peripheral) blood cellsERYTHROCYTESGRANULOCYTES (Eosinophil, Basophil, Neutrophil)MONOCYTESLYMPHOCYTES(Thrombocytes or Platelets)TO SUPPLY PERIPHERAL BLOOD CELLS
Cell hierarchyin the hematopoietic tissue
factors
THROMBOPOIESISTHROMBOCYTES
Differentiation and maturity of megakaryocyteBlood stem cellMegakaryocytic cellMegakaryocyteprecursor cell2N4N8N16N32NENDOMITOSISMATURITY OF CYTOPLASMMegakaryoblast / STAGE IPROMegakaryocyte / STAGE IIMegakaryocyte / STAGE IIIPRODUCTION OF PLATELETS
Hemostasisis the result of a series of process that tend to keep blood in the blood vessels. It involves the interaction of vessels, platelets, and coagulation factors. It is the normal state. Bleeding disorders are the result of abnormal hemostasis.
Components of hemostasisPrimary hemostasisTHE VASCULAR COMPONENT OF HEMOSTASIS(vasoconstriction, nervous reflex, local myogenic spasm) minutes to hoursTHE PLATELET COMPONENT OF HEMOSTASIS 3 7 minutesSecondary hemostasisTHE COAGULATION FACTOR COMPONENT OF HEMOSTASIS 3 10 minutes
THE VASCULAR COMPONENT OF HEMOSTASISThe ability of a blood vessel to1. constrict when injured, and 2. of the injured vascular subendothelium (collagen) to provide a functional surface for the subsequent formation of a platelet plug
THE PLATELET COMPONENT OF HEMOSTASIS (THE PLATELET PLUG)ADHESIONTHE RELEASE REACTIONAGGREGATIONPLATELET FACTOR 3 APPEARSCLOT RETRACTION
Bizzozero (Italian) 1881: piastrini (coin), German literature 1882: blutpattchen (platte = plate), Dekhuyzen 1901: thrombocyten, Wright 1910: blood plate, then later platelet
Adhesive Platelet Membrane Glycoprotein
PLATELETSare cytoplasmic fragments of megakaryocytes mother cellsrange in volume from 5 to 12 fLnormally, remain separated as they circulate in the bloodwhen activated (known as the release reaction), they secrete : from the dense bodies: adenosine diphosphate (ADP), adenosine triphosphate (ATP), serotonin, calcium ions, and from the a-granules: b-thromboglobulin (bTG), platelet factor 3 (PF3), platelet factor 4 (PF4), thrombospondin, fibrinogen, fibronectin, Factor V, Factor VIII, and von Willebrand factor (vWF)
PLATELETS perform 5 important functions in forming a plug (the platelet or trombocyte plug)ADHESIONS to underlying tissue when platelets encounter subendothelial structures (collagen, laminin)the RELEASE REACTION, in which they change shape (the microtubular system retracts concentrically) and release ADP, etc. biological substancesAGGREGATION of more platelets from the immediate areaPF3 appears on the platelet membrane and initiate the formation of a fibrin clotCLOT RETRACTION, a process produced by platelets trapped within the enlarging fibrin clot
PHYSIOLGY OF PLATELET FUNCTIONto exert normal functions, platelets have:receptors on their surface to bind substances like ADP, collagen, and vWFdense granules inside the platelet that contain ADP and serotonin (storage pool)microtubules and a canalicular system to release ADP and serotonin from the storage poola membrane component called PF3
PATHOPHYSIOLGY OF PLATELETSPLATELET DYSFUNCTION may be either acquired or hereditaryACQUIRED- drugs (NSAID: aspirin, indomethacin, butazolidin, sulfinpyrazone)- infection- etc.HEREDITARY
THE COAGULATION FACTOR COMPONENT OF HEMOSTASISTHE EXTRINSIC COAGULATION PATHWAYTHE INTRINSIC COAGULATION SYSTEMTHE COMMON PATHWAY
FIBRINOLYSIS
COAGULATION PATHWAY
THE CLOTTING FACTORS ARE SOLUBLE GLYCOPROTEINS IN THE BLOOD,and can be summarized as follows:THE EXTRINSIC COAGULATION PATHWAYis a rapid process, initiated by calcium ions and tissue thromboplastin, which results in the activation of factor VII. This, in turn, activates factor X, after which the reaction progresses down the common pathway. The function of the extrinsic system is measured by the prothrombin time (PT)
THE CLOTTING FACTORS ARE SOLUBLE GLYCOPROTEINS IN THE BLOOD,and can be summarized as follows:THE INTRINSIC COAGULATION SYSTEMprobably begins with the activation of factor XII and/or factor XI. A variaty of substances can be responsible for this activation. Factor XIa activates factor IX. Factor IXa and factor VIII form a complex that leads to the activation of factor X. Progression then follows the common pathway. The intrinsic system is measured by the activated-partial thromboplastin time (APTT)
THE CLOTTING FACTORS ARE SOLUBLE GLYCOPROTEINS IN THE BLOOD,and can be summarized as follows:THE COMMON PATHWAY.Factor Xa forms the crossroads of the 2 clotting systems. Factor Xa and II are bound to a phospholipid surface in the presence of factor Va. Factor II is then cleaved to form thrombin. Thrombin is required for the conversion of fibrinogen to fibrin, which then polymerizes to form a fibrin network.
NOMENCLATUREFACTOR:SYNONYMS:IFibrinogenIIProthrombinIIIThromboplastin, Thrombokinase, Tissue ExtractIVCalcium (ions)VLabile Factor, Proaccelerin, PlasmaAccelerator Globulin, Plasma Ac-GlobulinVNot assignedVIIStable Factor, Proconvertin, Autoprothrombin I, Serum Prothrombin
NOMENCLATUREFACTOR:SYNONYMS:VIIIAntihemophilic Factor, Antihemophilic Globulin Platelet Co-Factor I, Thromboplastinogen, Antihemophilic Factor AIXPlasma Thromboplastin Component, Christmas Factor, Platelet Co-Factor II, Autoprothrombin II, Antihemophilic Factor BXStuart Factor, Prower Factor, Stuart-Prower Factor, Autoprothrombin IIIXIPlasma Thromboplasti Antecedent, Antihemophilic Factor CXIIHageman Factor, Surface Factor, Contact Factor, Clot-Promoting FactorXIIIFibrin-Stabilizing Factor, Fibrin-Stabilizing Enzyme, Fibrinase, Laki-Lorand FactorPrekallikreinFletcher FactorHMW KininogenFitzgerald Factor
THE COAGULATION FACTORSWITH THE EXCEPTION OF FACTORSIIIThromboplastin, Thrombokinase, Tissue ExtractIVCalcium (ions)BLOOD COAGULATION FACTORS ARE PLASMA PROTEINS CIRCULATING IN THE BLOODSTREAM INAN INACTIVE STATE
COAGULATION PATHWAY
COAGULATION PATHWAY
COAGULATION PATHWAY
THE COAGULATION FACTORSTHE FACTORS are numbered according to theirdiscovery, not the order when participating in the clottingcascadeLIVER is responsible for the synthesis of coagulationfactors (also other cells e.g. megakaryocytes andendothelial cells), with the exception of part of Factor VIIIFACTORS II, VII, IX, X, protein C and protein S aredependent vitamin K for synthesis and normal activity
FORMATION OF FIBRIN CLOT
NATURAL INHIBITORS
THE CLOTTING FACTORS ARE SOLUBLE GLYCOPROTEINS IN THE BLOOD,and can be summarized as follows:FIBRINOLYSIS.As vascular healing occurs, the fibrin clot is degraded by the fibrinolytic enzyme, PLASMIN. Thus, the normal vascular integrity is restored.
FIBRINOLYSIS
FIBRINOLYSIS
ANTICOAGULATION FACTORSNaturally occuring:Antithrombin III (AT-III) inactivates free thrombinProtein C inactivates F V and F VIIIProtein S assists protein C in stimulating to release tPAAcquired / exogenous:LMW heparin enhancing the activity of AT-IIIHeparin enhancing the activity of AT-III
PATHOLOGY OF HEMOSTASISPATHOLOGY OF VASCULAR DEFECTSPATHOLOGY OF PLATELET DISORDERSPATHOLOGY OF COAGULATION FACTOR DISORDERS
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Evatt BL, Veltkamp JJ, Lewis SM, et al. Fundamental Laboratory Hematology: The Bleeding Disorders. U.S. Department of Health and Human Services, CDC Atlanta Georgia, and WHO Geneva Switzerland, 1990.
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