thrombosis, embolism and infarction

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Thrombosis, Embolism and Infarction. Dr. Raid Jastania. Hemostasis and Thrombosis. Hemostasis is the physiological process of maintaining blood in fluid state and formation of hemostatic plug at site of vessel injury. - PowerPoint PPT Presentation


  • Thrombosis, Embolism and InfarctionDr. Raid Jastania

  • Hemostasis and ThrombosisHemostasis is the physiological process of maintaining blood in fluid state and formation of hemostatic plug at site of vessel injury.Thrombosis is the pathological process of blood clotting in uninjured vessel or exagurated response to minimal injury.Components:Vessel wallPlateletsCoagulation pathways

  • Normal Hemostasis:Vessel injury - brief period of arteriolar vasoconstriction (neurogenic reflex ,endothelin)Endothelial injury exposes ECM (highly thrombogenic material). Platelets adhere to endothelial cells and ECM, and are activated. They release their secretory granules. Platelet aggregation occurs forming hemostatic plug (Primary hemostasis)Tissue factor (produced by endothelium) activates coagulation - formation of thrombin which act of finbrinogen to form fibrin (secondary Hemostsis)

  • Normal Hemostasis:The process continues to form the permanent plug formed by polymerized fibrin and platelet aggregates.

    At the same time tissue plasminogen activator (t-PA) is formed and it limits hemostatic plug.Fibrinolysis is also activated to limit heostatic plug to the site of injury.

  • Thrombosis:Thrombosis is the pathological process of blood clotting in uninjured vessel or an exaggerated blood clotting response to minimal injury.Virchow Triad: (factors predisposing thrombosis)Endothelial injuryBlood stasis or turbulence of blood flowBlood hypercoagulability

  • Endothelial InjuryAn important factor in arterial thrombosis.Occurs in myocardial infarction, ulcerated atherosclerosis, trauma, and inflammatory disease of vessels.Endothelial dysfunction is also a predisposing factor for thrombosis. Eg. Hypertension, bacterial endotoxins, hypercholestrolemia, radiation, cigarette smoking.Loss of endothelium will expose the ECM and hence activation of platelets and thrombosis.

  • Blood Stasis and Turbulence of FlowTurbulence enhances endothelial injury.Stasis enhances venous thrombosis.Both result in:Bringing platelets close to endotheliumAccumulation of clotting factorsPrevent clotting factors inhibitorsEndothelial activationExample: aortic aneurysm, MI, valve stenosis, rheumatic heart disease, hyperviscosity, sickle cell disease.

  • HypercoagulabilityIt is an alteration in coagulation leading to thrombosis.Primary: (genetic)Factor V mutationAntithrombin III deficiencySecondary:Prolonged immobilizationCancerLupus anticoagulantNephrotic syndromeContraceptive pillsSmoking

  • HypercoagulabilityHeparin-induced Thrombocytopenia:When heparin is administered it induces the formation of antibodies that bind platelets and activate them.Antiphospholipid syndrome (Lupus anticoagulant):Antibodies to phospholipid (eg. Cardiolipin)In-vitro: it inhibits coagulationIn-vivo: it induces coagulation

  • ThrombosisMay develop in the heart, arteries, veins and capillaries.Arterial thrombi and cardiac thrombi occur at site of endothelial injury or turbulence of flow.Venous thrombi occur in areas of blood stasis.Thrombi usually are attached to the underlying vessel wall (mural thrombi)Arterial thrombi grow back to the heart. Venous thrombi grow toward the heart.

  • ThrombosisArterial thrombi are firmly attached to the wall and show lines of Zahn (layers of fibrin and platelets alternate with layers of RBC and WBC.Venous thrombi do no show clear lamination.In the heart: common causes: MI, dilated cardiomyopathy, arrhythmia, myocarditis, or valvular disease.

  • ThrombosisIn arteries: common causes: atherosclerosis, and aneurysm.Arterial thrombi usually occlude the lumen, common in coronary, cerebral, and femoral arteries. Venous thrombi (phlebothrombosis) are almost always occlusive, Red thrombi, 90% occur in lower extremities.

  • Fate of thrombusPropagation (progression)EmbolizationLysis4.Organization and recanalization (inflammation and fibrosis)

  • Venous Thrombosis:Superficial: eg. Saphenous veinLocal congesion, edema, swelling, pain, tenderness, ischemia, risk of infectionRarely embolizeDeep Vein Thrombosis: eg. Popliteal, femoral, iliac veins.Can embolizeThere is a lot of collaterals so the congestion and edema are not prominent.50% are asymptomatic.

  • Venous ThrombosisBlood stasis is common predisposing factor for venous thrombosis. Eg. Heart failure, surgery, trauma, burn, pregnancy, cancer (Trousseau syndrome)

  • Cardiac and arterial thrombiMI, valve disease, arrhythmia, atherosclerosisPossible embolism to brain, kidneys, spleen.

  • Disseminated Intravascular CoagulationSudden widespread fibrin thrombi in the microcirculationOccurs in pregnancy, and with malignancy.Leading to circulatory insufficiency: brain , lung, heart, kidneysLeading to consumption of platelets and clotting factors and risk of bleeding.

  • Embolism

    Detached intravascular solid, liquid or gaseous mass carried by blood to a distant site.Types: Thrombus 90%, fat, air, cholesterol, tumor, bone marrow, foreign bodyOcclusion of vessels and ischemia/infarction

  • Pulmonary Thromboembolism20-25/ 100,000 of hospital patients95% coming from DVT (above knee)may occlude main pulmonary artery (Saddle embolus)or in small branches of vessels (multiple)Paradoxical embolus: cardiac embolus passing to the right side through septal defect.

  • Pulmonary Thromboembolism20-25/ 100,000 of hospital patients95% coming from DVT (above knee)may occlude main pulmonary artery (Saddle embolus)or in small branches of vessels (multiple)Paradoxical embolus: cardiac embolus passing to the right side through septal defect.

  • Pulmonary Thromboembolism60-80% are asymptomaticmost organizecan lead to cor pulmonale, sudden death.Result in hemorrhage, and rarely infarctionObstruction of small vessels lead to small infarctionsMultiple emboli may lead to pulmonary hypertension

  • Fat EmbolismAir EmbolismAmniotic Fluid Embolism

  • InfarctionIschemic necrosis caused by occlusion of arterial or venous vessles.Example: MI, cerebral infarction, pulmonary infarct, bowel infract, gangrene 99% due to thrombosis, mostly arterialCan be:VasospasmExternal pressureTraumaTwisting of organs eg. Testicular torsionEdema

  • InfarctionVenous infarct occurs in organs with single venous outflow. Eg. Testis, ovaryTypes: Red infarct, white infarct, septic infarctRed infarct:Due to venous occlusionIn loose tissue eg. LungOrgans with dual circulationIn tissues that have be previously congestedWhite infarctArterial occlusion of solid organs, eg. Heart, kidneys, spleen

  • InfarctionInfarction is usually wedge shape surrounded by rim of hyperemiaHemosiderin pigment may accumulate following hemorrhageNecrosis is of coagulative type (except brain: liquifactive)Inflammation within few hoursRepair process

  • Factors influencing development of InfarctNature of the blood supplyDual: lung, liver, handsEnd-arterial: spleen, kidneysRate of occlusion:Eg. Atherosclerosis of coronary arteries is gradual slow process

  • Factors influencing development of Infarct3. Vulnerability to hypoxiaNeuron: 3-4 minutesHeart: 20-30 minutesFibrous tissue: hours4. Oxygen content of the bloodEg. Heart failure patient have low oxygen concentration in blood

  • Normal Endothelium

    Endothelial cells are activated by injury, infection, plasma mediators and cytokines. They have pro-thrombotic and anti-thrombotic functions.

  • Anti-thrombotic properties:Anti-platelet effect:Non activated platelets do not adhere to endothelium.PGI2, and NO (produced by endothelium) prevent platelet adhesionAnticoagulant properties:Heparin-like molecule activate anti-thrombin IIIThrombomodulin binds thrombin which activate protein C (anticoagulant)Fibrinolytic properties:Endothelium synthesize t-PA (fibrinolysis)

  • Pro-thrombotic properties:Von Willebrand factor:It enhances binding of platelets to ECM.Tissue factorProduced by endothelium, it activates extrinsic clotting pathwayPlasminogen activator inhibitors (PAI)

  • Normal PlateletsPlatelets containAlpha-granules: P-selectin, fibrinogen, fibronectin, factor V, factor VIII, PDGF,TGF-alpha.Delta-granules: ATP, ADP, Ca, histamine, epinephrine

  • Normal PlateletsOn encountering ECM:1. Platelets adhere to ECM (collagen) mediated by vWF.2. Secrete their granules3.Platelets aggregate: forming the primary hemostatic plug which is reversible. With the action of thrombin, platelet contraction occur and the plug becomes irreversible (secondary hemostatic plug)

  • Normal PlateletsPGI2 inhibits platelet aggregationThromboxane A2 (TXA2) enhances platelet aggregationAspirin inhibits the synthesis of TXA2

  • Normal coagulation CascadeIt is series of enzymatic conversions turning inactive proenzymes to active forms.They lead to formation of thrombinThrombin converts fibrinogen to fibrin.Each reaction needs: enzyme, substrate, cofactor, phospholipid complex, Ca ionsTwo pathways: extrinsic and intrinsic: both lead to activation of factor X.

  • Intrinsic pathway is activated by activation of Hageman factor (factor XII).Extrinsic pathway is activated by tissue factor.The process is controlled by anticoagulants:Antithrombins (eg. Antithrombin III). It is activated by binding to Heparin-like molecule on endothelium.Protein C and S (vit K dependent) they inactivate factors Va and VIIIa.

  • Fibrinolytic cascade: While coagulation occursFactor XII or tissue plasminogen activator (t-PA) act on plasminogen to form plasmin.Plasmin start the process of fibrin lysis an the production of fibrin degradation produces.The function of plasmin is controlled (opposed) by plasminogen activator inhibitor (PAI) and alph2-antiplasmin.


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