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Scheme of Coagulation PowerPoint PPT Presentation


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F XII. F XIIa. Scheme of Coagulation. Intrinsic System. Extrinsic System. Foreign surface. Tissue damage Release of tissue thromboplastine (F III). F XI. F XIa. F X. F VIIa. F VII. F IX. F IXa. Ca 2+ PL. F VIII. F VIIIa. F XIII. Ca 2+ PL. Ca 2+. F II. F IIa. F XIIIa.

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Scheme of Coagulation

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Scheme of coagulation

F XII

F XIIa

Scheme of Coagulation

Intrinsic System

Extrinsic System

Foreign surface

Tissue damage

Release of tissue thromboplastine

(F III)

F XI

F XIa

F X

F VIIa

F VII

F IX

F IXa

Ca2+

PL

F VIII

F VIIIa

F XIII

Ca2+

PL

Ca2+

F II

F IIa

F XIIIa

Prothrombin

Thrombin

Ca2+

F IFibrino-gen

Fibrin-

monomer

Fibrins-

polymer

instabile

Fibrini-

polymer

stabile


Scheme of coagulation

Plasmatic Coagulation

  • start-and regulatorymechanism

  • Fibrin(strong, fibrousnetwork)

  • Fibrinogen(dissolved)

Ce 1297.76


Scheme of coagulation

Mechanism of AT III

  • inactive complex (TAT)

  • AT III

  • AT III

  • Thrombin

  • Thrombin

  • The effect of AT III is massively increased by heparin

Ce 1297.77


Scheme of coagulation

Most Important Inhibitorsof the Coagulation

  • Inhibitors

    • Antithrombin III

    • Protein C und protein S

  • Inactivation of

    • Thrombin

    • F Xa

    • F XIIa, F XIa, F VIIa

    • F VIIIa

    • F Va

Ce 1297.78


Scheme of coagulation

Regulation of Hemostasis

  • Anticoagulant Effect:

    • circulation of factors ininactiv form

    • blocking due to inhibitors

    • FXII caused activation of fibrinolyses

    • micro- undmacrocirculation

    • including of plasminogen

  • Procoagulant Effect:

    • release ofplatelet factors

    • increase due to coagulationcascade

    • accelerating factorsVa and VIIIa

    • availability of factorson endothelial surface


Scheme of coagulation

Regulatory Effect of the Endotheliumon Hemostasis

  • Procoagulant Effect:

    • surface/receptors for activation of coagulation factors

    • release of tissue thromboplastine

    • neutralisation of heparin

    • activation of F XII

  • Antifibrinolytic Effect:

    • release of plasminogen-activatorinhibitor 1 (PAI 1)

    • Anticoagulant Effect:

      • neutralisation/bindingof thrombin

      • activation of the protein C/S systems

      • release of „tissue factorpathway inhibitor“(versus F VIIa, F Xa)

  • Fibrinolytic Effect:

    • release of tpA

  • Ce 1297.80


    Scheme of coagulation

    Regulatory Effect of the Endotheliumon Hemostasis

    • Procoagulant Effect:

      • surface/receptors for activation of coagulation factors

      • release of tissue thromboplastine

      • neutralisation of heparin

      • activation of F XII

  • Antifibrinolytic Effect:

    • release of plasminogen-activatorinhibitor 1 (PAI 1)

    • Anticoagulant Effect:

      • neutralisation/bindingof thrombin

      • activation of the protein C/S systems

      • release of „tissue factorpathway inhibitor“(versus F VIIa, F Xa)

  • Fibrinolytic Effect:

    • release of tpA

  • Ce 1297.80


    Scheme of coagulation

    The Plasmatic Coagulation

    • Start mechanism:- contact with foreign surface (F XII, F XI)- release of tissue thromboplastin

    • Course:- cascading activation of different coagulation factors

    • Goal:- conversion of fibrinogen into fibrin

    • Regulation:- interaction of endothelium, platelets,plasmatic coagulation system, inhibitorsand fibrinolytic system

    Ce 1297.82


    Scheme of coagulation

    The Physiological Balance of Blood Coagulation

    Balance between coagulation factors (F)and inhibitors (I)

    F

    I

    • lack of factors

    • lack of inhibitors

    F

    I

    I

    F

    • risk of bleeding

    • risk of thromboses


    Scheme of coagulation

    Physiology of Coagulation

    • damage of the vessel wall

    • vasoconstriction,local decrease of blood pressure

    • activation of the thrombocytic system

    • activation of theplasmatic coagulation

    • activationof thefibrinolyses

    regulation

    by

    inhibitors

    and

    endothelium

    • formation of a fibrin-platelet-clot

    • wound closure/hemostasis

    • tissue reconstitution/wound healing

    • In case of coagulation disorders bleedings, thromboses and/or disturbed wound healing might occur!

    Ce 1297.85


    Scheme of coagulation

    Physiological Interactionsof the Coagulation System

    Coagulation

    ComplementSystem

    Wound Healing

    Inhibitors

    Fibrinolyses

    KininSystem

    activated byF XIII

    regulation

    of coagulation-processes

    degradationof the clot

    lysis of bacteria

    decreased blood pressure,

    increased

    vessel permeability

    adequate hemostasis §optimale tissue reconstitution


    Scheme of coagulation

    The Consequences of a Pathophysiological Escalation of the Coagulation System

    Pathological Coagulation

    Kinin Systeme

    Faktors

    Inhibitors

    F XIII

    Complement

    micro-

    and macro-thromboses

    edema,

    Capillary-Leak-

    Syndrom

    disturbedwound healing

    anaphylatoxins

    bleeding

    hypovolemia,shock

    hypotonia

    organ failure,

    shock

    rupture of wounds,fistula

    shock

    shock

    organ failure

    severe, partly life-threatening diseases

    Ce 1297.87


    Scheme of coagulation

    Lability of Hemostasis

    injury of the endothelium

    bleeding in the surrounding tissue

    physiological reaction

    pathophysiological escalation

    insufficient

    activation of coagulation/

    ecalating fibrinolyses

    escalating

    activation of coagulation/

    insufficient fibrinolyses

    local activationof coagulation andfibrinolyses

    continuous bleeding

    thromboses

    local hemostasis

    normal

    wound healing

    disturbed or absent wound healing

    Ce 1297.88


    Scheme of coagulation

    Coagulation Disorder Caused by Sepsis

    Infection

    Sepsis

    Severe sepsis

    with refractive

    hypotonia

    Activation of coagulation (DIC)

    Bleeding

    Micro- and Macro-

    thromboses

    Shock

    Multiple organ failure

    In case of severe infections the consequences of sepsis and coagulation disorders are increasing

    Ce 1297.89


    Scheme of coagulation

    Diagnostics of Coagulation Disorders

    More or less standardized laboratory tests for documentation are existent for the monitoring of the coagulation :

    • Function of vessels

    • Platelets

    • Plasmatic coagulation

    • Inhibitors

    • Fibrinolytic system

    • Activation parameters ofcoagulation and fibrinolyses

    Ce 1297.90


    Scheme of coagulation

    Diagnostics of Coagulation Disorders

    • Global tests:- Thrombelastogramm(plasmatic coagulation, fibrinolyses,platelets)- Bleeding time (number and function of platelets, plasmatic coagulation)

    • Function of vessels:- Rumpel-Leede-Test

    • Platelets:- Counting- Tests for adhesion and aggregation

    • Plasm. coagulation:- Screening tests (PT, PTT, TT)- Single factors- Inhibitors

    Ce 1297.91


    Scheme of coagulation

    Diagnostics of Coagulation Disorders

    • Fibrinolyses:- Plasminogen- Plasminogen activator inhibitor (PAI)

    • Marker ofhyperfibrinolyses:-Fibrin(ogen) degradation product (FDP) -Fibrin degradation products (FDP)- Plasmin- antiplasmin complex (PAP)

    • Marker of activationof the coagulation:-Fibrin-monomers-Prothrombin fragments F1+ F2-Thrombin-antithrombin (TAT) complex

    Ce 1297.92


    Scheme of coagulation

    Minimal Laboratory Programm for Coagulation

    • PT

    • PTT

    • Platelet count

    In case of pathological results or possible coagulation disorders further investigation is mandatory!

    Ce 1297.93


    Scheme of coagulation

    Monitoring of Intensive Care Unit Patients

    • PT

    • PTT

    • Platelet count

    • Antithrombin III

    • Fibrinogen

    • Bleeding time

    • Thrombin time

    • F XIII and othersingle factors (F V, F II)

    Ce 1297.94


    Scheme of coagulation

    Screening Tests of Plasmatic Coagulation

    PTT

    XII

    XI

    IX

    PTT

    XII

    XI

    IX

    PT

    V II

    PT

    V II

    V III

    X

    V

    II

    I

    TT

    X III

    Ce 1297.95


    Scheme of coagulation

    Diagnosis of Thrombotic Risk

    The available parameters detect only a third of all patients at risk:

    • Inhibitors:

    • Factors:

    • Marker of consumption:

    • Fibrinolyses:

    • Lupus-anticoagulants:

    AT III,Protein C,Protein S

    F XIIFibrinogen,F V (APC-resistance)

    TAT, F1+ F2,Fibrin-monomers

    PAI, PAP, FSP,D-dimers

    Plasminogen

    Lupus-anticoagulants

    Ce 1297.96


    Platelet adhesion

    Platelet Adhesion

    TXA2

    ADP

    • blood plateletWF as binding proteinfor collagen and platelets

    damaged endothelium

    subendothelial tissue (collagen)

    • Damage of endothelium and release of subendothelial structures (collagen)

    • Platelet adhesion on collagen influenced by von Willebrand factor

    • Activation of adhesed platelets

    • Release of Thromboxan A2 (TXA2) and ADP for aggregation of further platelets

    Ce 1297.73


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