Endothelial

injury

Thrombosis
Hyper- Abnormal
coagulability blood flow
 Loss of endothelium

Subendothelial ECM exposed

Platelets adhesion

Tissue factors released

Local PGI2 and PAs

PGI2 vasodilator & platelet aggregation inhibitor

PAs --> Plasminogen Activator, stimulates fibrinolysis
Endothelial dysfunction (not
necessarily denuded)
Hemodynamic stresses of
hypertension
Turbulent flow over scarred valves
Bacterial endotoxins
 Homocystinuria
Hypercholesterolemia
Radiation
Cigarette smoke
 Endothelial
injury/dysfunction

Turbulence
Form countercurrents
& local products of
stasis
Stasis is the major
factor in the
development of
venous thrombi.
 Disrupt laminar flow

Platelets in contact with the endothelium

Prevent dilution of activated clotting
factors by fresh flowing blood
 Stasis and turbulence

Retard the flow of clotting factor inhibitors

Permit build up of thrombi

 Stasis and turbulence

Promote endothelial cell activation

Predispose local Leukocyte Other endothelial
thrombosis adhesion cell effects
 Secondary
Primary (genetic)
(acquired)
 Common
Mutation in factor V gene (factor V Leiden)
Mutation in prothrombin gene
Mutation in methyltetrahydrofolate gene
Rare
Antithrombin III deficiency
Protein C deficiency
Protein S deficiency
Very rare
Fibrinolysis defects
 Factor V gene and prothrombin gene are the
most common.
Patients <50 y/o (w/ thrombosis w/o any
acquired predisposition)
Inherited cause of hypercoagulability
suspected.
 High risk for thrombosis
Prolonged bed rest or immobilization
Myocardial infarction
Atrial fibrillation
Tissue damage (surgery, fracture, burns)
Cancer
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
Smoking
 Caused by different
kinds of mechanism
Cardiac failure or trauma

Stasis or vascular injury

Hypercoagulability

Thrombosis
Oral contraceptive and hyperestrogenic state of pregnancy

hepatic coagulation factors synthesis and antithrombin

III synthesis

Hypercoagulability

Thrombosis
 Disseminated Cancer

Release of procoagulant tumor products

Hypercoagulability

Thrombosis
 Old age

Increased susceptibility to platelet aggregation and reduced

PGI2

Hypercoagulability

Thrombosis
 Administration of unfractionated heparin

Formation of antibodies

Antibodies bind to molecular complexes of heparin and platelet factor 4 membrane

protein (or other similar complexes on platelets or endothelial surfaces)

Platelet activation

Endothelial injury
 Thrombus accumulate more platelets and fibrin
Propagation. (propagate), eventually leading to vessel
obstruction.

Thrombi dislodge and travel to other sites in the

Embolization. vasculature.

Dissolution. Thrombi removed by fibrinolytic activity.

Organization Thrombi induce inflammation and fibrosis

(organization) and eventually become recanalized;
and that is, reestablish vascular flow, or incorporated
recanalization. into a thickened vascular wall.
Thrombi
Cause obstruction of
arteries and veins.
Possible sources of
emboli
Venous Cause congestion and
edema in vascular beds
thrombi distal to an obstruction

Lung Death
embolism
 Abnormal
vascular flow &
Atherosclerosis Thromboses loss of
endothelial
integrity
Mural Thrombi. Laminated thrombus in a dilated
abdominal aortic aneurysm.
 Myocardial infarction

Cardiac mural thrombi

Dyskinetic contraction of the myocardium &

damage to the adjacent endocardium
Mural thrombi. Thrombus in the left and right ventricular
apices, overlying a white fibrous scar
Cardiac and arterial (in
particular, aortic) mural
thrombi can also embolize
peripherally.
Any tissue may be affected (brain,
kidneys, and spleen are prime
targets because of their large flow
volume)
NOTE: Thrombosis
is still an
UNPREDICTABLE
phenomenon!!!