thrombosis in body

8/13/2019 Thrombosis in Body

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NORMAL HEMOSTASIS

After injury and vessel rupture Brief period of vasoconstriction(reflex neurogenic

mechanism at the arteriole level).

Attraction of plateletsto site of ruptureattracted by the

exposed subendothelial extracellular matrix. Activation of the coagulation system(by tissue factor and

secreted platelet factors); The activated coagulation systemproduces polymerized fibrin.

Adherent platelets + aggregated fibrin + entrapped bloodcells form a hemostatic plug.

Counterregulatory mechanisms are activated to limitpropagation of the hemostatic plug to the injury site.


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HemostasisA protective processthat provides for the rapid generation of alocalized hemostatic plug at the site of a vascular injury - while

maintaining clot-free blood in normal vessels.Thrombosis

An inappropriate activation of the hemostaticprocessleading tothe formation of a clot (thrombus)inside a blood vessels

during life, obstructing the flow of blood through the circulatorysystem.apathologic process

. Thromboembolismis a general term describing both

thrombosis and its main complication which is

embolisation.they are of variable size and shape ,depending

on causes.
http://en.wikipedia.org/wiki/Embolismhttp://en.wikipedia.org/wiki/Embolism


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Thrombosis


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VESSEL WALL

COLLAGENTISSUE FACTOR

CLOTPLATELETS

INTRINSIC

PATHWAY EXTRINSIC

PATHWAY

COMMON PATHWAY

Fibrinogen FibrinThrombin

HEMOSTATIC SYSTEM


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Causes

Classically, thrombosis is caused by abnormalities inone or more of the following (Virchow's triad):

Changes in the composition of the blood favouringplatelet aggregation and fibrin formation

(hypercoagulablility). Quality of the vessel wall(endothelial damage or

altered endothelial function)eg.thrombi on endocardium , MI ,orulcerated atheromatous plaques in artery walls.bacterial toxin.

Nature of the blood flow (slowing and perturbation)

stasis as in polycythemia or aneurysms results in loss of laminar blood flow andallow platelets to adher to the endothelium also allow the local accumulation ofactivated coagulation factor.turbulence causes reduction in endothelial PGI2 and t-PA formation
http://en.wikipedia.org/wiki/Rudolf_Virchowhttp://en.wikipedia.org/wiki/Rudolf_Virchow


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THROMBOSIS

Virchows TRIANGLEENDOTHELIAL

INJURY

ABNORMAL FLOW

(NON-LAMINAR)

HYPER-

COAGULATION


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ENDOTHELIAL INJURYany perturbation in the dynamic balance

of the pro- and antithrombotic effects ofendothelium, not only physical damage


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ENDOTHELIUM ANTI-Platelet PROPERTIES

Protection from the subendothelial ECM

Degrades ADP (inhib. Aggregation)

ANTI-Coagulant PROPERTIES Membrane HEPARIN-like molecules

Makes THROMBOMODULIN Protein-C TISSUE FACTOR PATHWAY INHIBITOR

FIBRINOLYTIC PROPERTIES (TPA)

PROTHROMBOTIC PROPERTIESMakes vWF, which binds

PlatsCollMakes TISSUE FACTOR (with plats

Makes Plasmino en inhibitors


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ABNORMAL FLOW

NON-LAMINARFLOW TURBULENCE EDDIES

STASIS

DISRUPTED ENDOTHELIUM

ALL of these factors may bring plateletsinto contact with endothelium and/orECF


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1HYPERCOAGULABILITY(INHERITED)

COMMONEST: Factor V and Prothrombindefects

Common: Mutation in prothrombin gene,Mutation in methyltetrahydrofolate gene

Rare: Antithrombin III deficiency, Protein C

deficiency, Protein S deficiency Very rare: Fibrinolysis defects


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2 HYPERCOAGULABILITY

(ACQUIRED)

Prolonged bed rest or immobilization

Myocardial infarction

Atrial fibrillation

Tissue damage (surgery, fracture, burns)

Cancer (TROUSSEAU syndrome, i.e., migratory thrombophlebitis)

Prosthetic cardiac valves

Disseminated intravascular coagulation

Heparin-induced thrombocytopenia

Antiphospholipid antibody syndrome (lupus anticoagulant syndrome)

Lower risk for thrombosis: Cardiomyopathy

Nephrotic syndrome

Hyperestrogenic states (pregnancy)

Oral contraceptive use

Sickle cell anemia Smokin Obesit


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ARTERIAL/CARDIAC THROMBI ACUTE MYOCARDIAL INFARCTION = OLD

ATHEROSCLEROSIS + FRESH THROMBOSIS ARTERIAL THROMBI also may send fragments

DOWNSTREAM, but these fragments may

contain flecks of PLAQUE also LODGING is PROPORTIONAL to the % of

cardiac output the organ receives, i.e., brain,

kidneys, spleen, legs, or the diameter of the

downstream vessel


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Atherosclerosis is characterized by intimal lesions calledatheromas, or atheromatousor fibrofatty plaques, that protrude

into and obstruct vascular lumina, weaken the underlying media,

and may undergo serious complications.
http://www.robbinspathology.com/content/lightbox.cfm?action=add&ImgID=F011007&ImgBody=graphics/S01871-011-f007.jpg&ID=iBoxhttp://www.robbinspathology.com/content/lightbox.cfm?action=add&ImgID=F011007&ImgBody=graphics/S01871-011-f007.jpg&ID=iBox


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ATHEROSCLEROTIC PLAQUE

NORMAL ARTERY ATHEROSCLEROTIC

PLAQUE


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60% Narrowing of Coronary Artery


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90% Blockage of Coronary Artery

calcified arearemaining lumen


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Thrombus Causing MI

needle-like white spots are cholesterol crystals


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Atherosclerotic Plaque Histology

cholesterol crystal (cleft) foam cells


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Myocardial Infarction Histology

necrosed muscle cells red blood cells


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Myocardial Infarction Histology

normal muscle cells remaining macrophages and the

beginnings of scar tissue


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Type of thrombi (appearance)

White thrombi (pale) Arterial: blood flow

rapid,firm aggregate of plt, fibrin, fewWBC/RBC

Red thrombi :venous:; blood flow slower,soft

dark red: RBC trapped in fibrin mesh

Mixed: pale and red(laminated appearance)

ADHERENCE TO VESSEL WALLHEART (MURAL)

ARTERY (OCCLUSIVE/INFARCT)VEIN

OBSTRUCTIVE vs. NON-OBSTRUCTIVE

RED, YELLOW, GREY/WHITE

ACUTE, ORGANIZING, OLD


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Sequels of Block

Collateral circulation:

Ischemia,

Infarction,Gangrene

Haemorrhage

f


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Fate of thrombus

Spread (propagation)Accumulation of moreplatelets and fibrin, becoming larger

Detachment: to form embolus(embolization) Removal (dissolution)

1. shrinkage of thrombus by contraction

2.lysis by plasmin and proteolytic enz

3.organization-digestion by macrophageand ingrowth of fibrovascular ts.

4.endothelialization,incorporation into vessel

wall by growth of endothelum over its

surface Organization and recanalizationthrombi may induce inflamation and fibrosis(organization)and

may eventually recanalized or they may be incorporatedinto a thickened vascular wall.


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SCHEMATIC ON THE FATE OF A THROMBUS

thrombosis in body

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