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YOGESH

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19 views

YOGESH

Uploaded by

ajju750netam
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© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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T OF

PATHOLOGY
Thrombosis
Presented by:- Moderator:-
Dr Deepika Dhruw Ma’am
Yogesh Kumar Baghel(124)
Anuj Maravi (127)
Contents
1. Introduction.
2. Normal hemostasis.
3. Role of different cells and processes in hemostasis
4. Pathophysiology of thrombosis.
5. Types of thrombi.
6. Morphologic features.
7. Fate of thrombus.
Introduction
• Thrombosis is the process of formation of solid mass in the
circulation from the constituents of the blood; the mass itself is
called a thrombus.
• Thrombus is a pathological manifestation which occurs when there is
a disruption or disregulation in the processes governing hemostasis
which under physiological conditions form a haemostatic plug.
Normal hemostasis
• Hemostasis is a precisely orchestrated process
involving platelets, clotting factors, and
endothelium that occurs at the site of vascular
injury and culminates in the formation of a blood
clot, which serves to prevent or limit the extent
of bleeding.
• The general sequence of events leading to
hemostasis at a site of vascular injury are:-
a. Arteriolar vasoconstriction.
b. Primary hemostasis: The formation of platelet
plug.
c. Secondary hemostasis: deposition of fibrin.
Events in hemostasis part 1
a. Arteriolar vasoconstriction occurs
immediately and markedly reduces blood flow
to the injured area. It is mediated by reflex
neurogenic mechanisms and by factors such as
endothelin.
b. Primary hemostasis: Disruption of the
endothelium exposes subendothelial von
Willebrand factor (vWF) and collagen, which
promote platelet adherence and activation.
Within minutes the secreted products recruit
additional platelets, which undergo aggregation
to form a primary hemostatic plug.
Events in hemostasis part 2
c. Secondary hemostasis: Tissue factor is also
exposed at the site of injury this tissue factor
activates factor VII leading to thrombin generation.
Thrombin cleaves circulating fibrinogen into
insoluble fibrin, creating a fibrin meshwork and
consolidating the initial platelet plug.
d. Clot stabilization and resorption. Fibrin and
platelet aggregates undergo contraction to form a
solid permanent plug that prevents further
hemorrhage. At this stage, counterregulatory
mechanisms are set into motion that limit clotting
to the site of injury.
Role of platelets
• Platelet adhesion is mediated largely via
interactions of vWF and collagen with platelet
surface receptor glycoprotein lb.
• Platelets than change their shape and translocate
negatively charged phospholipids to the platelet
surface.
• Platelets release granule contents such as ADP
which itself activates platelets and Thromboxane
A2 which induces platelet aggregation.
• Platelet aggregation is cross linking of platelets by
fibrinogen binding to GpIIb receptor on platelet.
Coagulation cascade
Role of thrombin
• Conversion of fibrinogen into cross linked
fibrin.
• Platelet activation.
• Pro inflammatory effects.
• Anticoagulant effects.
Factors that limit coagulation
• One limiting factor is simple dilution; blood flowing
washes out activated coagulation factors.
• A second is the requirement for negatively charged
phospholipids, which are mainly provided by
activated platelets.
• However, the most important counterregulatory
mechanisms involve factors that are expressed by
intact endothelium adjacent to the site of injury.
• Activation of the coagulation cascade also starts a
fibrinolytic cascade that limits the size of clot.
Role of endothelium
• The balance between the anticoagulant and
procoagulant activities of endothelium often
determines whether clot formation, propagation,
or dissolution occurs.
• Normal endothelial cells express several factors
that inhibit procoagulant activities of platelets and
coagulation factors and that augment fibrinolysis.
• However when injured or exposed to
proinflammatory factors they lose their
Continued…
• Platelet inhibitory effects-An obvious effect
of intact endothelium is to serve as a
barrier that shields platelets from
subendothelial vWF and collagen they also
release factors such as PGI2, NO which
inhibit platelet acivation and aggrrgation.
• Fibrinolytic effects- Normal endothelial
cells synthesize t-PA, already discussed, as
a key component of the fibrinolytic
Anticoagulant effects of endothelium
Pathophysiology of
thrombosis
• The primary abnormalities that lead to thrombosis are:
(1) endothelial injury
(2) stasis or turbulent blood flow, and
(3) hypercoagulability of the blood
• These factors constitute the so-called Virchow triad.
• Thrombosis is one of the scourges of modern man,
because it underlies the most serious and common
forms of cardiovascular disease.
Virchow triad
1.Endothelial injury
• Vascular injury exposes the subendothelial ECM,
which is thrombogenic and thus plays an
important role in initiating thrombosis

• A number of factors and conditions may cause


vascular injury and predispose to the formation of
thrombi. These are described in the next slides.
Factors causing endothelial injury
1. Endocardial injury in myocardial infarction,
myocarditis, cardiac surgery, prosthetic valves.
2. Ulcerated plaques in advanced atherosclerosis.
3. Haemodynamic stress in hypertension.
4. Arterial diseases.
5. Diabetes mellitus.
6. Endogenous chemical agents such as
hypercholesterolaemia, endotoxins.
7. Exogenous chemical agents such as cigarette
smoke
2. Alteration in blood flow
• Turbulence means unequal flow while stasis means
slowing
• Normally, there is axial flow of blood in which the most
rapidly-moving central stream consists of leucocytes
and red cells and platelets.
• Turbulence and stasis occur in thrombosis in which the
normal axial flow of blood is disturbed. When blood
slows down, the platelets come in contact with the
endothelium.
• Turbulence may actually injure the endothelium
resulting in deposition of platelets and fibrin.
Factors leading to altered blood flow
• Aortic and arterial dilations called aneurysms
result in local stasis and are therefore fertile sites
for thrombosis
• Mitral valve stenosis results in left atrial dilation;
in conjunction with atrial fibrillation, a dilated
atrium is a site of profound stasis and a prime
location for thrombosis.
• Hyperviscosity Seen with polycythemia vera
causes small vessel stasis.
• And the deformed red cells in sickle cell anemia
impede blood flow through small vessels, with the
resulting stasis also predisposing to thrombosis.
3.Hypercoagulability
• Thrombophilia or hypercoagulable states are
a group of conditions having increased risk
or predisposition to develop venous
thrombosis. These conditions may be
hereditary (or primary) or acquired (or
secondary) causes.
Primary hypercoagulability
1. Deficiency of antithrombin III.
2. Deficiency of protein C and S.
3. Mutation in factor V Leiden This is a autosomal
dominant disorder in which the mutation lies in
replacement of arginine by glycine at position
506. It is the most common cause of
thrombophilia.
4. Defects in fibrinolysis These include a few rare
inherited disorders such as dysfibrinogenaemia
and plasminomgen disorders.
5. Increased levels of coagulations factors (II and
VIII).
Secondary hypercoagulability
Complications of thrombosis
• Thrombi developing in the unruptured
cardiovascular system may be life-threatening by
causing one of the following harmful effects:
1. Ischaemic injury- Thrombi may decrease or
stop the blood supply to part of an organ or tissue
and cause ischaemia which may subsequently result
in infarction.
2. Thromboembolism Thrombus or its part may
get dislodged and be carried along in the
bloodstream as embolus to lodge in a distant vessel.
Origin of Thrombi at Different Sites

• Thrombi may arise from the heart,


arteries, veins or in microcirculation by
different mechanisms.
• Types of thrombi on the basis of site of
origin are:
1. Cardiac Thrombi
2. Arterial Thrombi
3. Venous Thrombi
Cardiac Thrombi
• Thrombi may form in any of the chambers of the
heart and on the valve cusps. They are more
common in the atrial appendages, especially of
the right atrium, and on mitral and aortic valves
such as vegetations seen in infective endocarditis
• Cardiac thrombi are non occlusive or mural
thrombi. Rarely, large round thrombus may form
in the mitral valve and is called ball-valve
thrombus.
Arterial thrombi VS Venous thrombi
Capillary thrombi

• Minute thrombi composed mainly of


packed red cells are formed in the
capillaries in acute inflammatory
lesions, vasculitis and in disseminated
intravascular coagulation (DIC).
Morphologic features
• Grossly, Arterial thrombi tend to be white and mural
while the venous thrombi are red and occlusive.
Mixed or laminated thrombi are also common and
consist of alternate white and red layers called lines
of Zahn. Red thrombi are soft, red and gelatinous
whereas white thrombi are firm and pale.
• Microscopically, the lines of Zahn are formed by
alternate layers of light-staining aggregated platelets
admixed with fibrin meshwork and dark-staining
layer of red cells. Red (venous) thrombi have more
abundant red cells, leucocytes and platelets
entrapped in fibrin meshwork.
Fate of thrombus
1. RESOLUTION Thrombus activates the fibrinolytic
system which may dissolve the thrombus.
2. ORGANISATION If the thrombus is not removed, it
starts getting organised. Phagocytic cells begin to
phagocytose fibrin and cell debris. Capillaries grow
into the thrombus and fibroblasts start invading the
thrombus. Thus, fibrovascular granulation tissue is
formed and it becomes part of vessel wall
3. PROPAGATION The thrombus may enlarge in size
due to more and more deposition
4. THROMBOEMBOLISM The thrombi may get
detached from the vessel wall and get released in
blood-stream as emboli.
Fate of thrombus
Thank
you!

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