thrombosis- dr. shubhangi v. agale
TRANSCRIPT
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Dr. Shubhangi AgaleAssociate ProfessorGrant Govt Medical College, Mumbai.
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Functions of Normal HemostasisMaintain blood in a fluid and clot free state
Induce a rapid and localised hemostatic plug at a site of vascular injury
Hemostasis and thrombosis are regulated by: the vascular wall, platelets, and the coagulation cascade
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Normal flow of liquid blood is maintained by following properties of endothelial cells
Antiplatelet properties
Anticoagulant properties
Endothelium
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ThrombosisDefinition:
Formation of solid
plug any where in
intact cardiovascular
system from
constituents of blood
during life.
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Differential Diagnosis1. Blood clot: A mass of coagulated blood
formed in vitro e.g. in a test tube.
2. Haematoma: Extra vascular accumulation of blood clot e.g. into the tissues.
3. Haemostatic plug: Blood clots formed in a healthy individual at the site of injury.
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Effects of Thrombosis :“ Life threatening”
1. Ischaemic injury: Thrombi may decrease/ stop the blood supply to part of an organ/ tissue and cause ischaemia which may subsequently result in infarction.
2. Thromboembolism: The thrombus or its part may get dislodged and be carried along in the blood stream as embolus to lodge in a distant vessel e.g. Pulmonary embolism.
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Pathogenesis
Three primary influences predispose to thrombus formation (Virchow triad)
Endothelial injury Stasis or turbulence of blood flow Hypercoagulability of blood
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1. Endothelial Injury1. Role of vessel wall.2. Role of Platelets.3. Role of coagulation system.
Role of vessel wall:-Integrity of vessel wall is important to maintain normal blood flow.
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Endothelial InjuryIntact endothelium has following functions- 1. Protects the flowing blood from
thrombogenic influence of subendothelium.2. Elaborates few anti thrombotic factors like
heparin like substance,thrombomodulin,inhibitors of platelet aggregation,fibrinolysis-TPA.
3. Release of prothrombotic factors-Thromboplastin,von Willibrand’s factor,platelet activating factor,inhibitor of TPA.
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A leads to –Exposure of subendothelium
( collagen, elastin, fibronectin,laminin, glycosaminoglycans)which are Thrombogenic.
Brief vasoconstriction of small blood vessels –to reduce the blood flow.
Major significance in arterial thrombi/in heart.
Vasculr injury::
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Conditions where vascular injury predispose to formation of thrombiEndocardial injury in myocardial infarction, cardiac surgery, prosthetic valves.
Ulcerated plaques in athrosclerosis.Hypertension, Diabetis Mellitus, cigarette smoking.
Arterial diseases.
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Endothelial dysfunction without endothelial loss
Hemodynamic stresses of HypertensionTurbulent flow over scarred valvesBacterial toxinsHomocystinuriaHypercholesterolemiaRadiationProducts absorbed from cigarette smoke
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2. Alteration in Normal Blood FlowTurbulence a) Causes endothelial injury or
dysfunction, b) Forms counter currents and local
pockets of stasis
Stasis: Disrupts normal blood flow
Normal blood flow (Laminar): Platelets flow centrally separated from the endothelium by plasma
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Stasis and TurbulenceBring platelets into contact with
endotheliumPrevent dilution of clotting factorsRetard inflow of clotting factor inhibitor
and permit the build-up of thrombiPromote endothelial cell activation,
predisposing to local thrombosis
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2. Alteration of blood flowFormation of arterial and cardiac thrombi is
facilitated by turbulence in the blood flow.Stasis initiates the venous thrombi even
without evidence of endothelial injury.In turbulence and stasis, the normal axial
flow of blood is disturbed so that the platelets come into contact with the endothelium.
Inhibitors of coagulation fail to reach the site of thrombus resulting in enlargement of the thrombus site.
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3. Hypercoagulability
Any alteration of the coagulation pathways that predisposes to thrombosis.
A) Primary or Genetic. 1. Mutation in factor V gene (Leiden)
2. Mutation in Prothrombin gene. 3. Mutation in Methyltetrahydrofolate gene.
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4. Rarea) Antithrombin III deficiencyb) Protein Cc) Protein S deficiency
d) Fibrinolysis defects
Hypercoagulability
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Hypercoagulability Secondary (Acquired): A) High risk:
1. Prolonged bed rest/immobilisation2. Myocardial infarction,3. Atrial fibrillation4. Tissue damage(surgery, fracture, burns, cancer)
5. Prosthetic cardiac valves,6. DIC
7. Heparin induced thrombocytopenia 8. Antiphospholipid antibody
syndrome
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Gross appearanceArterial thrombi-White, mural, firm ,pale.
Venous thrombi- red, occlusive, soft, gelatinous.
Mixed or laminated- Alternate red & white layers –Lines of Zahn.
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Types of thrombiAntemortem Thrombi.1. Gross-
Dry,granular,firm,friable
2. Adherant to vessel wall.
3. Shape- May or may not fit their vascular contours.
4. Surface contains apparent lines of Zahn.
Postmortem clots.1. Gross-Gelatinous,
soft, rubbery.2. Weakly attached.3. Take the shape of
vessel or its bifurcation.
4. The surface is chicken fat yellow covering the underlying red currant jelly.
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MicroscopyComposition depends upon rate of flow
of blood.
Lines of Zahn are formed by light staining aggregated platelets admixed with fibrin and dark staining layer of red cells.
Red thrombi have more abundant red cells leucocytes & platelets entrapped in fibrin meshwork.
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Sites for ThrombiAny where in cardiovascular systemVariable in size and shape Arterial: at ulcerated Atherosclerotic
plaque Cardiac: MIAuricular appendage, Stenotic
valveVessel bifurcation due to turbulenceVenous thrombi: At site of stasisFirmly attached at the point of originArterial: Thrombi grow retrogradeVenous: Thrombi extend towards heart
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Mitral valve stenosis
Atrial fibrillation
Stasis due to hyperviscosity syndrome (Polycythemia)
Deformed red cells (Sickle cell anemia)
Clinical settings contributing to thrombosis
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Cardiac ThrombiVegetations of infective endocarditis.
Maccallum patch in RHD.
Myocardial infarction-subendocardial.
Ball valve thrombus.
Atrial appendages.
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Arterial ThrombiUsually occlusiveSites: Coronary, Cerebral, FemoralThrombus on atherosclerotic plaque or sometimes vasculitis
Firmly adherent to injured endothelium
Gray-white, friable
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Arterial thrombiAorta:aneurysms,arteritis.Coronary arteries:atherosclerosis.Mesentric artery:atherosclerosis,arteritis.Arteries of limbs:atherosclerosis,diabetes
mellitus, Buerger’s disease, Raynaud’s disease.
Renal artery: atherosclerosis,arteritis.Cerebral artery:atherosclerosis,vasculitis.
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Venous thrombiVeins of lower limbs:deep veins of
legs,varicose veins.Popliteal,femoral and iliac
veins:postoperative stage,postpartum.Pulmonary veins:CHF,pulmonary
hypertensionHepatic and portal vein:portal hypertensionSuperior vena cava:infections in head and
neckMesentric veins:volvulus,intestinal
obstruction
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Arterial vs Venous ThrombusGrossly: Thrombi are friable, a mixture of red
and gray in irregular layers, dull, and attached to the endothelium
Arterial thrombus: Dry, friable gray masses composed of almost regularly arranged layers of platelets and fibrin, irregularly mixed with small amounts of darker red coagulated blood (White or conglutination thrombus)
Venous thrombus: Red, gelatinous(Stasis or red coagulation thrombus)
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Capillary ThrombiVasculitis.
Acute inflammatory lesions.
Disseminated intravascular coagulation.
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Fate of ThrombusPropagation: May accumulate more platelet and fibrin leading to fibrosis and inflammation
Recanalisation: Reestablish vascular obstruction
Embolisation: Thrombi may dislodge Dissolution: Removed by fibrinolytic activity
Organisation: Thrombi may induce flow
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Predisposing FactorsPrimary(Genetic)factors:
1. Defficiency of antithrombin,Protien C / S.2. Defects in fibrinolysis.3. Mutation in Factor V.
Secondary (acquired) factors:1. Prolonged bed rest / Immobilisation.2. Use of oral contraceptives.3. Cigarette smoking.4. Tissue damage: trauma,fractures,burns.
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1. Heart diseases- MI, CHF, RHD, Cardiomyopathy.
2. Atherosclerosis.3. Aneurysms of Aorta.4. Varicose veins.5. Nephrotic syndrome.6. Dissseminated cancers.
Clinical conditions predisposing to thrombosis
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Clinical Effects of ThrombosisCardiac thrombi- sudden death,
thromboembolism
Arterial thrombi- sudden death, thrombosis of coronary artery
Venous thrombi-thromboembolism, skin, thrombophlebitis,
Capillary thrombi- DIC
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Clinical Correlation
Arterial Thrombi: Obstruction of coronary arteries (Myocardial infarction), cerebral, Renal arteries, and arteries of spleen
Venous Thrombi: Congestion and edema distal to obstruction, may
embolise to lung (Pulmonary embolism) causing death
Superficial venous Thrombi: Congestion, swelling, pain, tenderness (rarely embolise)
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Clinical CorrelationDeep Venous Thrombi: (Popliteal,
femoral, Iliac)Occurs in cardiac failure due to stasisImmobalisationRelease of procoagulant substances
from tissues: Puerperium, Amniotic fluid infusion into circulation in delivery
Hypercoagulability: late pregnancy, Postpartum period
Release of tumor associated procoagulant
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SUMMARYDefinitionEffects of thrombiPathogenesisVirchow’s triadAntemortem / postmortem thrombiGross appearanceMicroscopy Types of thrombiFate of thrombusPredisposing FactorsClinical Effects of Thrombosis
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