HEMOSTASIS (Hemo = blood ;

Stasis = halting)

• Normal hemostasis comprises a series of regulated

processes that MAINTAIN blood in a fluid, clot-free state
in normal vessels while rapidly forming a localized
hemostatic plug at the site of vascular injury.

10/16/2022 Dr. Ashish Lakhey

 Hemostasis

Sequence of responses that

stop bleeding

3 Steps to stop bleeding:

A) Primary Hemostasis
(1) Vascular spasms
(2) Platelet plug formation
B) Secondary Hemostasis
(3) Coagulation, or blood clotting

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10/16/2022 Dr. Ashish Lakhey
 Fibrinolytic System
Method for removing clots and maintenance of a patent
vascular system and fibrin deposited during inflammation
and tissue injury must be removed.

–Plasmin (serine protease) primarily responsible for

fibrinolysis.
– Produced in the liver and kidney, it circulates in an inactive
form (plasminogen).
– While plasminogen is normally found in blood and body
fluids, plasmin is usually absent due to numerous
antiplasmins.
• Inactivators: antithrombin III, a2-macroglobulin, a1-
antitrypsin and C1 inactivator.

10/16/2022 Dr. Ashish Lakhey

 Thrombosis

 It is a process by which a thrombus is formed.

 A thrombus is an adherent intravascular coagulation

(PATHOLOGICAL clot ) (solid mass of blood
constituents) which develops in intact artery or vein.

 Often causes significant interruption to blood flow.

 It is composed of varying proportions of coagulation

factors, RBCs and platelets.

10/16/2022 Dr. Ashish Lakhey

 Pathogenesis

Three primary influences predispose to thrombus

formation, the so-called VIRCHOW’S TRIAD:

(1) Endothelial injury

(2) Stasis or turbulence of blood flow
(3) Blood hypercoagulability

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 VIRCHOW’S TRIAD

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Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 1 April 2005 07:37 PM)
© 2005 Elsevier
 A) Endothelial Injury
 This is the dominant influence to thrombus formation.
 Endothelial injury is particularly important in thrombus
formation in the heart (E.g. Myocardial infarction) and arterial
circulation (Vasculitis), atherosclerosis, hypertension).
 Overt loss of endothelium exposes subendothelial
ECM
 Net effect: Increased prothrombotic effect than the
antithrombotic effect.
- E.g. Reduces local production of PGI2 and
plasminogen activators
- Increases platelet adhesion molecules, tissue
factor, PAI (Plasminogen activator inhibitor)

10/16/2022 Dr. Ashish Lakhey

 B) Alterations in Normal Blood Flow

• Turbulence contributes to arterial and cardiac thrombosis

by causing endothelial injury or dysfunction as well as by
forming countercurrents and local pockets of stasis.

• Stasis is a major factor in the development of venous

thrombi.

10/16/2022 Dr. Ashish Lakhey

 B) Alterations in Normal Blood Flow

Stasis and Turbulence:

1) Disrupt laminar flow and bring platelets into contact with the
endothelium.

2) Prevent dilution by fresh flowing blood of activated clotting

factors.

3) Retard the inflow of clotting factor inhibitors and permit the

build-up of thrombi.

4) Promotes endothelial cell activation, predisposing to local

thrombosis, leukocyte adhesion and a variety of other
endothelial cell effects.

10/16/2022 Dr. Ashish Lakhey

 Hypercoagulability

• Hypercoagulability contributes less frequently to

thrombotic states.

• Can be genetic or acquired;

A) Genetic: Mutations in the factor V gene is most
common (Leiden mutation),
B) Acquired: -Heparin-induced thrombocytopenia and
thrombosis syndrome
- Antiphospholipid antibody syndrome

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 Fate of Thrombus

If the patient survives the thrombotic vascular obstruction

thrombi may undergo:

1) Propagation : The thrombus enlarges.

2) Embolization: Part or all of the thrombus is dislodged and
transported elsewhere in the vasculature.
3) Dissolution: If a thrombus is newly formed, activation of
fibrinolytic factors may lead to its rapid shrinkage and
complete dissolution.
4) Organization And Recanalization: Ingrowth of endothelial
cells, smooth muscle cells, and fibroblasts into the fibrin-
rich thrombus.
Capillary channels are formed.

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 Fate of Thrombus

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 Thrombi: Clinical Correlation

Can cause -
1) Cause obstruction of arteries and veins
2) Are possible sources of emboli

The significance of each depends on where the thrombus

occurs

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 Venous Thrombosis (RED thrombus)

• The great preponderance of venous thrombi occur in

either the superficial or deep veins of the leg.

• In veins the circulation is sluggish and the thrombi are

primarily composed of a dark red mass of fibrin within
which are entrapped RBCS, white blood cells and a
few platelets.

10/16/2022 Dr. Ashish Lakhey

 Arterial Thrombosis (PALE thrombus)

• Atherosclerosis is a major initiator of thromboses,

related to abnormal vascular flow and loss of endothelial
integrity.

• In arteries there is rapid blood flow and the thrombi are

composed of platelets with some fibrin and appear firm
and pale.

10/16/2022 Dr. Ashish Lakhey

 Morphology of Thrombi

 Thrombi can have grossly (and microscopically)

apparent laminations called LINES OF ZAHN; these
represent pale platelet and fibrin layers alternating with
darker red cell–rich layers.

 Lines of Zahn are only found in thrombi that form in

flowing blood. (Helps to differentiate antemortem
thrombus from postmortem thrombus)

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10/16/2022 Dr. Ashish Lakhey