Thrombosis

Hemostasis A protective process that provides for the rapid generation of a localized hemostatic plug at the site of a vascular injury - while maintaining clot-free blood in normal vessels.

Thrombosis
An inappropriate activation of the hemostatic process leading to the formation of a clot (thrombus) inside a blood vessels during life, obstructing the flow of blood through the circulatory system. a pathologic process

. Thromboembolism is a general term describing both thrombosis and its main complication which is embolisation.they are of variable size and shape ,depending on causes.

NORMAL HEMOSTASIS
After injury and vessel rupture
Brief period of vasoconstriction (reflex neurogenic mechanism at the arteriole level). Attraction of platelets to site of rupture attracted by the exposed subendothelial extracellular matrix.

Activation of the coagulation system (by tissue factor and secreted platelet factors); The activated coagulation system produces polymerized fibrin.
Adherent platelets + aggregated fibrin + entrapped blood cells form a hemostatic plug. Counterregulatory mechanisms are activated to limit propagation of the hemostatic plug to the injury site.

HEMOSTATIC SYSTEM
INTRINSIC
PATHWAY
COMMON PATHWAY EXTRINSIC PATHWAY

Thrombin Fibrinogen Fibrin

PLATELETS

CLOT

COLLAGEN

TISSUE FACTOR

VESSEL WALL

Causes
Classically, thrombosis is caused by abnormalities in one or more of the following (Virchow's triad): Changes in the composition of the blood favouring platelet aggregation and fibrin formation (hypercoagulablility). Quality of the vessel wall(endothelial damage or altered endothelial function) eg.thrombi on endocardium , MI ,or
ulcerated 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 and allow platelets to adher to the endothelium also allow the local accumulation of activated coagulation factor.turbulence causes reduction in endothelial PGI2 and tPA formation

 Virchows TRIANGLE
ENDOTHELIAL INJURY

THROMBOSIS

ABNORMAL FLOW (NON-LAMINAR)

HYPERCOAGULATION

ENDOTHELIAL INJURY
any perturbation in the dynamic balance of the pro- and antithrombotic effects of endothelium, not only physical damage

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 PROPERTIES

Makes vWF, which binds PlatsColl Makes TISSUE FACTOR (with plats) Makes Plasminogen inhibitors

ABNORMAL FLOW NON-LAMINAR FLOW

TURBULENCE EDDIES STASIS DISRUPTED ENDOTHELIUM ALL of these factors may bring platelets into contact with endothelium and/or ECF

1 HYPERCOAGULABILITY
(INHERITED)

COMMONEST: Factor V and Prothrombin

defects

Common: Mutation in prothrombin gene,

Mutation in methyltetrahydrofolate gene

Rare: Antithrombin III deficiency, Protein C

deficiency, Protein S deficiency

Very rare: Fibrinolysis defects

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) Cardiomyopathy Nephrotic syndrome Hyperestrogenic states (pregnancy) Oral contraceptive use Sickle cell anemia Smoking, Obesity

Lower risk for thrombosis:

 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

ARTERIAL/CARDIAC THROMBI

Atherosclerosis

is characterized by intimal lesions called atheromas, or atheromatous or fibrofatty plaques, that protrude into and obstruct vascular lumina, weaken the underlying media, and may undergo serious complications.

ATHEROSCLEROTIC PLAQUE

NORMAL ARTERY

ATHEROSCLEROTIC PLAQUE
15

60% Narrowing of Coronary Artery

90% Blockage of Coronary Artery

remaining lumen

calcified area

Thrombus Causing MI

needle-like white spots are cholesterol crystals

Atherosclerotic Plaque Histology

cholesterol crystal (cleft) foam cells

Myocardial Infarction Histology

necrosed muscle cells red blood cells

Myocardial Infarction Histology

normal muscle cells remaining macrophages and the beginnings of scar tissue

Type of thrombi (appearance)

White thrombi (pale) Arterial: blood flow rapid,firm aggregate of plt, fibrin, few WBC/RBC Red thrombi :venous:; blood flow slower,soft dark red: RBC trapped in fibrin mesh Mixed: pale and red(laminated appearance)
ADHERENCE TO VESSEL WALL
HEART (MURAL) ARTERY (OCCLUSIVE/INFARCT) VEIN

OBSTRUCTIVE vs. NON-OBSTRUCTIVE RED, YELLOW, GREY/WHITE ACUTE, ORGANIZING, OLD

Sequels of Block
Collateral circulation: Ischemia, Infarction, Gangrene Haemorrhage

Fate of thrombus
Spread (propagation) Accumulation of more
platelets 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 macrophage and ingrowth of fibrovascular ts. 4.endothelialization,incorporation into vessel wall by growth of endothelum over its surface

Organization and recanalization

thrombi may induce inflamation and fibrosis(organization)and may eventually recanalized or they may be incorporated into a thickened vascular wall.

SCHEMATIC ON THE FATE OF A THROMBUS