Thrombosis

Dr Aarathi Rau

Hemostasis

• Normal hemostasis: the end result of a set of well regulated processes that accomplish

• fluid blood in the normal blood vessel

• Rapid & localized hemostatic plug at the site of vessel injury.

Normal hemostasis• Arteriolar constriction• Exposure of extracellualar matrix (ECM) beneath

the endothelium• Adherence of platelets to form platelet plug• Activation of platelets & degranulation

(ADP,thrombin, thromboxane A2) • Tissue factor (from injury) stimulate coagulation

cascade• Fibrin clot & platelets form secondary hemostatic

plug• Limit size of clot by fibrinolysis

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© 2005 Elsevier

Thrombosis

• Definition: the pathological process characterized by intravascular clotting in a living person.

• Thrombus: intravascular clot

• Formed from the constituents of blood

• Occurs in an uninjured vessel or after relatively minor injury.

Virchows triad

• Endothelial injury

• Stasis or abnormal blood flow

• hypercoagulability

Endothelium• PROTHROMBOTIC

• vWF---platelet adherence

• Thromboplastin • PAF-----------fibrin

formation

• inhibitors pf Plasminogen activator ( PA I)---depresses fibrinolysis

• ANTITHROMBOTIC

• Antiplatelet: NO ,PGI 2 –vasodilators block platelet adherence & aggregation

• Anti coagulant • Thrombomodulin• Antithrombin III-interferes

with clotting

• Tissue type Plasminogen activator (t PA) promotes fibrin lysis

Causes of endothelial injury• Hemodynaminc injury e.g. hypertension

• Atherosclerosis

• Inflammation (thrombophlebitis)

• Autoimmune diseases e.g.Polyarteritis nodosa (PAN)

• Metabolic:hyperlipidemia,homocystinemia

• Trauma

• Infections

Altered blood flow

• Turbulent flow (disruption of normal laminar flow)- arterial

• stasis (venous)

• Platelets & WBC’s in contact with endothelial cells

Effects of altered blood flow

• Activation of endothelial cells so that procoagulant > anticoagulant

• Prevent removal of platelets and

• Prevent fresh anticoagulants from blood reaching endothelium

• Stasis-dilated veins

• Mechanical damage of endothelium

Altered composition of blood• Hypercoagulability• Heriditary: deficiency of Protein C/S,Factor V

Leiden,Antithrombin III (AT III)• Hyperhomocystinemia (acquired or congential )• Acquired • tissue damage - thromboplastin• Tumour, bacteria,smoking • Autoimmune :SLE,PAN• Antiphospholipid antibodies

Formation of a thrombus

• Virchows triad predisposes

• Platelets adhering to site of endothelial injury

• Fibrin

• RBC’s +Fibrin+Platelets

• Lines of Zahn

• Propogation

Morphology of thrombus

• Lines of Zahn platelets+ fibrin alternating with fibrin + RBC’s+ platelets

• Attached to vessel wall

• Friable along the lines of Zahn

• Moulded to blood vessel

Site of Thrombi• Arterial -Coronary, cerebral, femoral

• Site of endothelial injury (AS), turbulence (bifurcation)

• Venous-

• Lower extremities(90%)-superficial /deep veins of legs

• Ovarian,periuterine,portal hepatic vein

in sites of stasis

Site of Thrombi (cont.)• Cardiac (usual mural)

– ventricles: site of endothelial injury, MI, dilated cardiomyopathy

– atria: occur in sites of stasis, Atrial Fibrillation

• Heart Valves (vegetations)– infective endocarditis– non-bacterial thrombotic endocarditis– Verrucous (Libman-Sacks )endocarditis

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© 2005 Elsevier

Mural Thrombi

Arterial Vs Venous thrombus• Arterial –lines of Zahn more prominent

paler in colour usually occlusive, retrograde

propagation• Venous –less prominent lines of Zahn

red/ darker in colour(like clotted blood)Invariably occlusive, propagate in direction

of blood flow/towards the heart • Post mortem clot: not friable, not attached

to blood vessel, currant jelly, chicken fat

Fate of /Outcome of thrombus• Dissolution-fibrinolysis of RECENT

thrombi• Propagation-grow downstream• Embolization-detach& travel elsewhere in

circulation• Organization-granulation tissue grows into

the thrombus• Recanalization-blood vessels fuse into

larger channels allowing resumption of blood flow.

Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 27 June 2005 07:26 PM)

© 2005 Elsevier

Potential Outcomes Of Venous Thrombosis

Common causes of thrombosis• T –Tissue damage• H- Heriditary -deficiency of ProteinC/S,

Factor V Leiden,Antithrombin III• R- Rest• O –Obstetric • M- Malignancy (Trosseau syndrome )• B- Blood flow disturbances• I- Immune mechanisms

SLE,Antipholspolipid Ab, PAN

Clinical importance of thrombi

• Cause obstruction of arteries and veins

• Possible source of emboli

Clinical complications • Arterial & cardiac thrombosis-Infarction, CAD• Systemic Embolization • Venous obstruction –Oedema,DVT• Pulmonary Emboli • Infection –secondary infection,mycotic aneurysm• Inflammation of vessel wall –thrombophlebitis• Trosseau syndrome-migratory thrombophlebitis

associated with internal malignancy due to procoagulant substances.

MCQ’s

• In which of the following conditions are lines of Zahn seen?

• Post mortem clot

• Primary platelet clot

• Corraline thrombus

• Clot in sample bottle

• In which of the following conditions are lines of Zahn seen?

• Post mortem clot

• Primary platelet clot

• Corraline thrombus √

• Clot in sample bottle

• Which is the earliest step in the formation of a thrombus?

• Formation of fibrin

• Adherence of platelets to vascular sub endothelium

• Activation of clotting factor VII

• Trapping of RBC’s

• Which is the earliest step in the formation of a thrombus?

• Formation of fibrin

• Adherence of platelets to vascular sub endothelium √

• Activation of clotting factor VII

• Trapping of RBC’s

SHORT ANSWER QUESTIONS

• Fate of a thrombus

• Virchows triad

• Predisposing factors for thrombosis

• Difference between post-mortem clot and thrombus

CLINICAL IMPORTANCE

• Major cause of morbidity and mortality