Dr. Shubhangi AgaleAssociate ProfessorGrant Govt Medical College, Mumbai.

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

Normal flow of liquid blood is maintained by following properties of endothelial cells

Antiplatelet properties

Anticoagulant properties

Endothelium

ThrombosisDefinition:

Formation of solid

plug any where in

intact cardiovascular

system from

constituents of blood

during life.

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.

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.

Pathogenesis

Three primary influences predispose to thrombus formation (Virchow triad)

Endothelial injury Stasis or turbulence of blood flow Hypercoagulability of blood

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.

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.

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::

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.

Endothelial dysfunction without endothelial loss

Hemodynamic stresses of HypertensionTurbulent flow over scarred valvesBacterial toxinsHomocystinuriaHypercholesterolemiaRadiationProducts absorbed from cigarette smoke

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

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

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.

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.

4. Rarea) Antithrombin III deficiencyb) Protein Cc) Protein S deficiency

d) Fibrinolysis defects

Hypercoagulability

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

Gross appearanceArterial thrombi-White, mural, firm ,pale.

Venous thrombi- red, occlusive, soft, gelatinous.

Mixed or laminated- Alternate red & white layers –Lines of Zahn.

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.

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.

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

Mitral valve stenosis

Atrial fibrillation

Stasis due to hyperviscosity syndrome (Polycythemia)

Deformed red cells (Sickle cell anemia)

Clinical settings contributing to thrombosis

Cardiac ThrombiVegetations of infective endocarditis.

Maccallum patch in RHD.

Myocardial infarction-subendocardial.

Ball valve thrombus.

Atrial appendages.

Arterial ThrombiUsually occlusiveSites: Coronary, Cerebral, FemoralThrombus on atherosclerotic plaque or sometimes vasculitis

Firmly adherent to injured endothelium

Gray-white, friable

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.

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

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)

Capillary ThrombiVasculitis.

Acute inflammatory lesions.

Disseminated intravascular coagulation.

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

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.

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

Clinical Effects of ThrombosisCardiac thrombi- sudden death,

thromboembolism

Arterial thrombi- sudden death, thrombosis of coronary artery

Venous thrombi-thromboembolism, skin, thrombophlebitis,

Capillary thrombi- DIC

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)

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

SUMMARYDefinitionEffects of thrombiPathogenesisVirchow’s triadAntemortem / postmortem thrombiGross appearanceMicroscopy Types of thrombiFate of thrombusPredisposing FactorsClinical Effects of Thrombosis