#1 kuliah basic principle and lab test for thrombosis and fibrinolysis

Upload: joshua-obrien

Post on 03-Jun-2018

224 views

Category:

Documents


0 download

TRANSCRIPT

  • 8/12/2019 #1 Kuliah Basic Principle and Lab Test for Thrombosis and Fibrinolysis

    1/22

    MECANISM HEMOSTASIS & FIBRINOLYSIS

  • 8/12/2019 #1 Kuliah Basic Principle and Lab Test for Thrombosis and Fibrinolysis

    2/22

    Hemostasis or haemostasis is a complex process which causes the bleedingprocess to stop.

    Intact blood vessels are central to moderating blood's tendency to clot.

    The endothelial cells of intact vessels prevent thrombus ("clot") formation by

    1.secreting tissue plasminogen activator (t-PA)

    2.inactivating thrombin and adenosine diphosphate (ADP).

    Injury to vessels overwhelms these protective mechanisms and hemostasis

    ensues.

    HEMOSTASIS IS MAINTAINED IN THE BODY VIA THREE MECHANISMS:

    1.Vascular spasm - Damaged blood vessels constrict..( vascular spasmmaintained by serotonin and epinefrin)

    2.Platelet plug formation - Platelets adhere to damaged endothelium to form

    platelet plug (primary hemostasis) and then degranulate.

    3.Blood coagulation - Clots form upon the conversion of fibrinogen to fibrin,

    and its addition to the platelet plug (secondary hemostasis).

  • 8/12/2019 #1 Kuliah Basic Principle and Lab Test for Thrombosis and Fibrinolysis

    3/22

    Damage to small blood vessels and capillaries frequently occurs.

    When these vessels are damaged, there are three basic mechanismsthat promote hemostasis or the stoppage of bleeding.

  • 8/12/2019 #1 Kuliah Basic Principle and Lab Test for Thrombosis and Fibrinolysis

    4/22

    Following damage, there is an immediate reflex that promotes

    VASOCONSTRICTION/VASO SPASM ,thus diminishing blood loss.

    Exposed collagen from the damaged site will promote the PLATELETS TO

    ADHERE.

  • 8/12/2019 #1 Kuliah Basic Principle and Lab Test for Thrombosis and Fibrinolysis

    5/22

  • 8/12/2019 #1 Kuliah Basic Principle and Lab Test for Thrombosis and Fibrinolysis

    6/22

    When platelets adhere to the damaged vessel, they undergo degranulation and release

    cytoplasmic granules,which contain

    1.Serotonin, a vasoconstrictor,

    2.ADP and

    3.Thromboxane A2.

  • 8/12/2019 #1 Kuliah Basic Principle and Lab Test for Thrombosis and Fibrinolysis

    7/22

    The ADP attracts more platelets to the area, and the thromboxane A2 promotes

    platelet aggregation, degranulation, and vasoconstriction.Thus ADP and thromboxane A2 promote more platelet adhesion and therefore

    more ADP and thromboxane.

    The positive feedback promotes the formation of a platelet plug.

    THE FINAL HEMOSTATIC MECHANISM IS COAGULATION.

  • 8/12/2019 #1 Kuliah Basic Principle and Lab Test for Thrombosis and Fibrinolysis

    8/22

    Damaged tissue releases factor III, which with the aid of Ca++ will activate factor VII, thus

    initiating the extrinsic mechanism.

    Factor XIIfrom active platelets will activate factor XI, thus initiating the intrinsic

    mechanism.

  • 8/12/2019 #1 Kuliah Basic Principle and Lab Test for Thrombosis and Fibrinolysis

    9/22

    Both active factor VII and active factor XI will promote cascade reactions, eventually

    activating factor X.

  • 8/12/2019 #1 Kuliah Basic Principle and Lab Test for Thrombosis and Fibrinolysis

    10/22

    Active factor X, along with factor III, factor V, Ca++, and platelet thromboplastic factor (PF3), will

    activate prothrombin activator.

  • 8/12/2019 #1 Kuliah Basic Principle and Lab Test for Thrombosis and Fibrinolysis

    11/22

    Prothrombin activator converts prothrombin to thrombin.

    Thrombin converts fibrinogen to fibrin.

  • 8/12/2019 #1 Kuliah Basic Principle and Lab Test for Thrombosis and Fibrinolysis

    12/22

    Fibrin initially forms a loose mesh, but then factor XIII causes the formation of

    covalent cross links, which convert fibrin to a dense aggregation of fibers.

    Platelets and red blood cells become caught in this mesh of fiber, thus the

    formation of a blood clot

  • 8/12/2019 #1 Kuliah Basic Principle and Lab Test for Thrombosis and Fibrinolysis

    13/22

  • 8/12/2019 #1 Kuliah Basic Principle and Lab Test for Thrombosis and Fibrinolysis

    14/22

    FIBRINOLISIS

    1.Aktifasi Plasminogen menjadi plasmin

    2.Aktifator plasminogen : intrinsik: XII a,Kalikrein (dlm circ drh)ekstrinsik : t PA (dlm endothel pemb drh

    eksogen : Urokoinase

    3.Inhibitor plasmin

  • 8/12/2019 #1 Kuliah Basic Principle and Lab Test for Thrombosis and Fibrinolysis

    15/22

  • 8/12/2019 #1 Kuliah Basic Principle and Lab Test for Thrombosis and Fibrinolysis

    16/22

    Fibrinolysis is the process wherein a fibrin clot, the product of coagulation, is

    broken down.

    Its main enzyme plasmin cuts the fibrin mesh at various places, leading to the

    production of circulating fragments that are cleared by other proteases or by

    the kidney and liver.

    Plasmin is produced in an inactive form, plasminogen, in the liver.

    Although plasminogen cannot cleave fibrin, it still has an affinity for it, and is

    incorporated into the clot when it is formed.

  • 8/12/2019 #1 Kuliah Basic Principle and Lab Test for Thrombosis and Fibrinolysis

    17/22

    Tissue plasminogen activator (t-PA)and urokinase are the agents that convert

    plasminogen to the active plasmin, thus allowing fibrinolysis to occur.

    t-PA is released into the blood very slowly by the damaged endothelium of the

    blood vessels / after several days (when the bleeding has stopped), the clot is

    broken down.

    This occurs because plasminogen became entrapped within the clot when it

    formed; as it is slowly activated, it breaks down the fibrin mesh.

    t-PA and urokinase are themselves inhibited by plasminogen activator inhibitor-1

    and plasminogen activator inhibitor-2 (PAI-1 and PAI-2).

    In contrast, plasmin further stimulates plasmin generation by producing more

    active forms of both tPA and urokinase.

    Alpha 2-antiplasmin and alpha 2-macroglobulin inactivate plasmin.Measurement

    When plasmin breaks down fibrin, a number of soluble parts are produced.

    These are called fibrin degradation products (FDPs).

  • 8/12/2019 #1 Kuliah Basic Principle and Lab Test for Thrombosis and Fibrinolysis

    18/22

    Pharmacology

    Fibrinolytic drugs are given after a heart attack to dissolve the thrombus

    blocking the coronary artery, experimentally in stroke to reperfuse the affected

    part of the brain, and in massive pulmonary embolism. The process is called

    thrombolysis.

    Antifibrinolytics, such as aminocaproic acid (-aminocaproic acid) and tranexamic acid are used as inhibitors of fibrinolysis.

    Their application may be beneficial in patients with hyperfibrinolysis because they arrest bleeding rapidly if the other components of

    the haemostatic system are not severely affected.

    This may help to avoid the use of blood products such as fresh frozen plasma with its associated risks of infections or anaphylactic

    reactions. The antifibrinolytic drug aprotinin was abandoned after identification of major side effects, especially on kidney.

  • 8/12/2019 #1 Kuliah Basic Principle and Lab Test for Thrombosis and Fibrinolysis

    19/22

    Tissue plasminogen activator (abbreviated tPA or PLAT) is a protein

    involved in the breakdown of blood clots.

    As an enzyme, it catalyzes the conversion of plasminogen to

    plasmin,the major enzyme responsible for clot breakdown. Because

    it works on the clotting system, tPA is used in clinical medicine to

    treat only embolic or thrombolytic stroke.

    Use is contraindicated in hemorrhagic stroke and head trauma.

    tPA may be manufactured using recombinant biotechnology

    techniques.tPA created this way may be referred to as recombinant

    tissue plasimogen activator or rtPA.

  • 8/12/2019 #1 Kuliah Basic Principle and Lab Test for Thrombosis and Fibrinolysis

    20/22

    The classic role of tPA is in the clotting system.

    Specifically, tPA catalyzes the conversion of plasminogen into

    plasmin. It does so by cleaving the single-chained plasminogen into

    two chains. These two chains are linked by a disulfide bond and the

    resulting molecule is called plasmin.

    Increased enzymatic activity causes hyperfibrinolysis, whichmanifests as excessive bleeding. Decreased activity leads to

    hypofibrinolysis which can result in thrombosis or embolism.

  • 8/12/2019 #1 Kuliah Basic Principle and Lab Test for Thrombosis and Fibrinolysis

    21/22

    SCREENING TEST FOR BLEEDING DISORDERS :1. PLATELET COUNT

    Generaly spontaneous bleeding rarely occurs with platelet counts greater than 20.000 PER MM3.Surgically induced bleeding may be severe if the count range between 40.00070.000/mm3.

    2.BLEEDING TIME

    Bleeding time is prolong in disorders affecting the microvascular system, such as

    scurvy and the inherited collagen disorder Ehlers Danlos Syndrome.

    Hemophilia ( deficiency of factor VIII) , not to be characterized by prolong bleeding time, may

    manifest this abnormality in up 20 % of case.

    3.PROTHROMBIN TIME

    Pro long in :

    a. Levels of factors V, VII, X falls below 50 % and when prothrombin level are less than 30 % or

    normal.

    b.The fibrinogen level is less than 100 mg / dl.c.Fibrinogen level < 100 mg/Dl

    d.Severe hepato cellular disease

    e.DIC

    f.Vit K deficiency

    g.Monitor Warfarin therapy

  • 8/12/2019 #1 Kuliah Basic Principle and Lab Test for Thrombosis and Fibrinolysis

    22/22

    4.ACTIVATED PARTIAL THROMBOPLASTIN TIME

    - Measured the integruty of the entire intrinsic pathway of coagulation --- Sensitive to

    deficiency of all factors other than VII AND XIII

    - Prolong if any of intrinsic or common path way factors decrease.- Also prolong in presence of certain anticoagulants and is used to monitoring heparin

    therapy.

    5.FIBRINOGEN LEVEL

    - Concentration decrease in :

    DIC and severe liver disease