hemostasis dr. taj antithrombogenic thrombogenic vessel injury (favors fluid blood)(favors clotting)

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  • HEMOSTASIS Dr. TajAntithrombogenicThrombogenicVessel injury(Favors fluid blood)(Favors clotting)

  • 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 & clothing disorders

  • HEMOSTASISFrom an injured blood vessel is the

    Prevention of blood loss OrStoppage of bleedingOr Arrest of bleeding from a broken blood vessel

  • STEPS OF HEMOSTASISVascular SpasmFormation of platelet plugBlood CoagulationClot Retraction

  • VASCULAR SPASM(Vascular Constriction)FactorsNervous reflexesLocal myogenic spasmLocal humoral factorFor smaller vesselsPlatelets Thrombokanc A2ImportanceCenshing injuries Intense spasm No lethal loss of blood

  • FORMATION OF PLATELET PLUGImportance of platelet plug small vascular damage

  • 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 & blood proteinsBegins to develop in 15-20 sec Minor trauma1-2 min. Severe trauma

  • physical events of Clotting process

  • PLATELETS Formed by fragmentation from megakaryoctyes

  • PLATELETSContractile, adhesive, cell fragments.Store coagulation factors & 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

  • ACTIN AND MYOSIN MOLECULESTHROMBESTHENINENDOPLASMIC RETICULUM AND GOLGI APPARATUSMITOCHONDRIAENZYME SYSTEMS FOR SYNTHESIS OF PROSTAGLANDINSFIBRIN STABILIZING FACTORGROWTH FACTORFUNCTIONAL CHARACTERISTICS:

  • MECHANISMFormation of Prothrombin activator complexConversion of prothrombin into thrombinConversion of fibrinogen into fibrin

  • 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

  • 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

  • CONVERSION OF FIBRINOGEN TO FIBRIN Formation Of ClotFibrinogenMol. Wt. 340,000Plasma conc. 100 700 mg/dlSynthesized in liver

  • ACTION OF THROMBIN ON FIBRONOGEN TO FORM FIBRIN

  • BLOOD CLOTA meshwork of fibrin fibres running in all directions and entrapping blood cells, platelets and plasma

  • 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

  • Clotting Factors

  • EXTRINSIC MECHNANISM FOR INITIATING CLOTTING

  • INTRINSIC MECHNANISM FOR INITIATING CLOTTING

  • ROLE OF THROMBIN IN HEMOSTASIS

  • 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++

  • LYSIS OF BLOOD CLOTS PLASMINPlasminogen / Profibrinolysin

    T-PA

    Plasmin or Fibrinolysin

    Lysis of clot

  • 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

  • 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

  • BLEEDING & CLOTTING DISORDERSLiver diseases & Vitamin-K deficiencyHemophiliaThrombocytopenia

  • BLEEDING DISORDERSLiver diseases & Vitamin-K deficiencye.g. Hepatitis, CirrhosisDecreased formation of clotting factorsIcnreased clotting timeVitamin K dependent factorsProthrombin, Factor VII, IX, X

  • HEMOPHILIA HEMOPHILIA AClassic Hemophilia85 % casesDef. Of factor VIIIHEMOPHILIA B15 % casesDef. Of factor IX

  • THROMBOCYTOPENIA PLT count upto 50,000 ulLess than 10,000 ------ FatalETIOLOGYDecreased productionAplastic anemiaLeukemiaDrugsInfections (HIV, Measles)

  • HEMOPHILIAGenetic disordersTransmitted by female chromosome as recessive traitOccurs exclusively in male Females are carriersTypesHemophilia AHemophilia B

  • 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)

  • THROMBOCYTOPENIA Increased destructionITP DrugsInfectionsClinical FeaturesEasy brusabilityEpistaxisGum bleedingHemorrhage after minor traumaPetechiae/Ecchumosis

  • THROMBOCYTOPENIA DiagnosisPLT decreasedB.T increasedRxRx of the underlying causePLT concentratesFresh whole blood transfusionSplenectomy

  • THANK YOU

  • ANTI COAGULANTS FOR CLINICAL USEHeparin ---------- Subcutaneous or intramuscularWarfarin --------- Oral

  • 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

  • FEMORAL THROMBOSIS & MASSIVE PULMONARY EMBOLISMProlonged Immobilization Propping the knees with underlying pillowsIntravascular clot

    Grows up and down

    Clot disengages

    Venous blood

    Massive pulmonary embolism

  • 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

  • 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

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