HEMOSTASIS Dr. Taj Antithrombogenic Thrombogenic Vessel injury (Favors fluid blood)(Favors clotting)

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<ul><li><p>HEMOSTASIS Dr. TajAntithrombogenicThrombogenicVessel injury(Favors fluid blood)(Favors clotting)</p></li><li><p>OBJECTIVESAt the end of the lecture you should be able to describe..What is hemostasisWhat are the steps of hemostasisThe 2 pathways of coagulationThe role of platelets in hemostasisBleeding &amp; clothing disorders</p></li><li><p>HEMOSTASISFrom an injured blood vessel is the</p><p>Prevention of blood loss OrStoppage of bleedingOr Arrest of bleeding from a broken blood vessel</p></li><li><p>STEPS OF HEMOSTASISVascular SpasmFormation of platelet plugBlood CoagulationClot Retraction</p></li><li><p>VASCULAR SPASM(Vascular Constriction)FactorsNervous reflexesLocal myogenic spasmLocal humoral factorFor smaller vesselsPlatelets Thrombokanc A2ImportanceCenshing injuries Intense spasm No lethal loss of blood</p></li><li><p>FORMATION OF PLATELET PLUGImportance of platelet plug small vascular damage</p></li><li><p>BLOOD COAGULATION Formation Of ClotBlood clotting is the transformation of blood from a liquid into a solid gel formPathwaysIntrinsic ExtrinsicInitiated by: Activator substances from traumatized vascular wall, plts &amp; blood proteinsBegins to develop in 15-20 sec Minor trauma1-2 min. Severe trauma</p></li><li><p>physical events of Clotting process</p></li><li><p>PLATELETS Formed by fragmentation from megakaryoctyes</p></li><li><p>PLATELETSContractile, adhesive, cell fragments.Store coagulation factors &amp; enzymesSurface Binding sites for fibrinogenSurface Glycoprotein Antigens-HPA1.SHAPE: MINUTE ROUND OR OVAL DISCSSIZE: 1-4 um IN DIAMETERHALF LIFE: 8-12 DAYSCOUNT: 150,000 300,000/ microlitrer</p></li><li><p>ACTIN AND MYOSIN MOLECULESTHROMBESTHENINENDOPLASMIC RETICULUM AND GOLGI APPARATUSMITOCHONDRIAENZYME SYSTEMS FOR SYNTHESIS OF PROSTAGLANDINSFIBRIN STABILIZING FACTORGROWTH FACTORFUNCTIONAL CHARACTERISTICS:</p></li><li><p>MECHANISMFormation of Prothrombin activator complexConversion of prothrombin into thrombinConversion of fibrinogen into fibrin</p></li><li><p>INITIATION OF COAGULATIONFormation Of Prothrombin Activator Complex2 WaysBy Extrinsic pathway trauma to vascular wall and surrounding tissuesBy Intrinsic pathway trauma to the blood Is the rate - limiting factor</p></li><li><p>CONVERISON OF PRTHROMBIN TO THROMBIN By Prothrombin Activator ComplexProthrombinPlasma protein (Alpha2 globulin)Mol. Wt. - 68,700Plasma conc. - 15 mg/dlUnstable proteinSynthesized by liverVitamin-K is required for synthesis</p></li><li><p>CONVERSION OF FIBRINOGEN TO FIBRIN Formation Of ClotFibrinogenMol. Wt. 340,000Plasma conc. 100 700 mg/dlSynthesized in liver</p></li><li><p>ACTION OF THROMBIN ON FIBRONOGEN TO FORM FIBRIN</p></li><li><p>BLOOD CLOTA meshwork of fibrin fibres running in all directions and entrapping blood cells, platelets and plasma</p></li><li><p>CLOT RETRACTIONWhen clot contracts, it expresses most of the fluid from the clot within 20-60 min. SerumSERUM CANNOT CLOTROLE OF PLTS IN CLOT FORMATIONVICIOUS CIRCLE OF CLOT FORMATION</p></li><li><p>Clotting Factors</p></li><li><p>EXTRINSIC MECHNANISM FOR INITIATING CLOTTING</p></li><li><p>INTRINSIC MECHNANISM FOR INITIATING CLOTTING</p></li><li><p>ROLE OF THROMBIN IN HEMOSTASIS</p></li><li><p>ROLE OF CALCIUM IONS IN CLOTTINGNo Ca++ No ClottingBlood samples are prevented from clotting by adding:Citrate ions Deionization of Ca++Oxalate ions ppt the Ca++ </p></li><li><p>LYSIS OF BLOOD CLOTS PLASMINPlasminogen / Profibrinolysin</p><p>T-PA</p><p>Plasmin or Fibrinolysin</p><p>Lysis of clot</p></li><li><p>INTRAVASCULAR ANTICOAGULANTSEndothelial Surface FactorsSmoothness of EndotheliumGlycocalyx LayersThrombomodulin ProteinAntithrombin action of Fibrin and Antithrombin III85-90 % Thrombin binds with Fibrin10-15 % Thrombin binds with Antithrombin III</p></li><li><p>INTRAVASCULAR ANTICOAGULANTSHeparin- vely charged conjugated polysaccharideIncrease the effectiveness of Antithrombin IIIProduced by Mast cellsBasophil cellsMost widely used anticoagulant clinically e.g. in strokeAlpha2 MacrogobulinActs as a binding agent for several coagulation factors </p></li><li><p>BLEEDING &amp; CLOTTING DISORDERSLiver diseases &amp; Vitamin-K deficiencyHemophiliaThrombocytopenia</p></li><li><p>BLEEDING DISORDERSLiver diseases &amp; Vitamin-K deficiencye.g. Hepatitis, CirrhosisDecreased formation of clotting factorsIcnreased clotting timeVitamin K dependent factorsProthrombin, Factor VII, IX, X</p></li><li><p>HEMOPHILIA HEMOPHILIA AClassic Hemophilia85 % casesDef. Of factor VIIIHEMOPHILIA B15 % casesDef. Of factor IX</p></li><li><p>THROMBOCYTOPENIA PLT count upto 50,000 ulLess than 10,000 ------ FatalETIOLOGYDecreased productionAplastic anemiaLeukemiaDrugsInfections (HIV, Measles)</p></li><li><p>HEMOPHILIAGenetic disordersTransmitted by female chromosome as recessive traitOccurs exclusively in male Females are carriersTypesHemophilia AHemophilia B</p></li><li><p>HEMOPHILIA Clinical FeaturesEasy bruising, massive bleeding after trauma or operation, hemorrhages in jointsFactor VIII Small Comp. Hemophilia A Large Comp. Von-Willebrands diseaseRxInjection of factor VIII (Hemophilia A)Injection of factor IX (Hemophilia B)</p></li><li><p>THROMBOCYTOPENIA Increased destructionITP DrugsInfectionsClinical FeaturesEasy brusabilityEpistaxisGum bleedingHemorrhage after minor traumaPetechiae/Ecchumosis</p></li><li><p>THROMBOCYTOPENIA DiagnosisPLT decreasedB.T increasedRxRx of the underlying causePLT concentratesFresh whole blood transfusionSplenectomy</p></li><li><p>THANK YOU</p></li><li><p>ANTI COAGULANTS FOR CLINICAL USEHeparin ---------- Subcutaneous or intramuscularWarfarin --------- Oral</p></li><li><p>THROMOEMBOLIC CONDITIONSThrombusAbnormal clot that develops in a blood vesselEmbolusFreely flowing clotsEmboli from Lf heart or large arteries ------------Emboli from Rt heart or venous system ----------EtiologyRoughened Endothelia surfaceSluggish flow of bloodRxUse of genetically engineered t-PAUse of streptokinase</p></li><li><p>FEMORAL THROMBOSIS &amp; MASSIVE PULMONARY EMBOLISMProlonged Immobilization Propping the knees with underlying pillowsIntravascular clot</p><p>Grows up and down</p><p>Clot disengages</p><p>Venous blood</p><p>Massive pulmonary embolism</p></li><li><p>DISSEMINATED INTRAVASCULAR COAGULATIONResults fromPresence of large amounts of traumatized or dying tissue in the bodyReleases tissue thromboplastinClots are small and numerous Seen in Septicemic shock</p></li><li><p>BLEEDING DISORDERSVitamin-KFat soluble vitaminRequired by liver for formation 4 clotting factorsSourcesDietSythesized in the intestinal tract by bacteriaDeficiencyMalabsorption syndromesBiliary obstructionBroad spectrum antibioticsDietary def (in Neonates)Rx.: Treat the underlying cause Vit K injections</p></li></ul>