Thrombosis And Embolism of the general pathology

Normal hemostasis:
Is the end result of a set of well regulated
processes that accomplish:
1-fluid blood in the normal blood vessel
2-Rapid & localized hemostatic plug at
the site of vessel injury.

Normal hemostasis
• → transient arteriolar vasoconstriction
• Endothelial injury→
• Exposure of extracellular matrix (ECM) beneath the
endothelium→ platelets adhesion , activation and
aggregation(formation of initial platelet plug is called
primary hemostasis)
• Exposure of tissue factor (factor ‫׀׀׀‬ or
thromboplastin)→ with factor V‫׀׀‬ is the major in vivo
trigger of coagulation cascade
Vascular
injury

Endothelium
PROTHROMBOTIC
• vWF---platelet
adherence
• Thromboplastin
• PAF-----------fibrin
formation
• inhibitors pf
Plasminogen activator
( PA I)---depresses
fibrinolysis
ANTITHROMBOTIC
• Antiplatelet: NO ,PGI 2 –
vasodilators block platelet
adherence & aggregation
• Anti coagulant
• Thrombomodulin
• Antithrombin III-interferes
with clotting
• Tissue type Plasminogen
activator (t PA) promotes
fibrin lysis

The coagulation Cascade
It comprises:
 The tissue injury pathway (extrinsic)
 The contact pathway (intrinsic)
 The common pathway

• Fibrin clot & platelets form secondary
hemostatic plug
size of clot is Limited by:
thrombomodulin on endothelium→ binds
thrombin and convert it into anticoagulant
 activation of fibrinolytic pathway by
association of tissue plasminogen activator
with fibrin

Thrombosis
Definition of Thrombosis:
 Formation of solid mass of blood constituents
withinvascular system in life
 Definition of Thrombus:
Intravascular clot Formed from the constituents of
blood Occurs in an uninjured vessel or after
relatively minor injury.

Abnormalities that can lead to thrombus
formation include:
• Endothelial injury
• Stasis or turbulent blood flow
• Hypercoagulability of the blood
Virchow's
triad

Endothelial injury:
• Important in the heart and arteries
• e.g after MI in the cardiac chambers
• over ulcerated plaques in atherosclerotic
artery
• Vasculitis

Conditions lead to endothelial injury:
• Hypertension
• Turbulent blood flow
• Bacterial products
• Radiation injury
• Metabolic abnormalities e.g homocystinuria,
hypercholesterolemia

Endothelium dysfunction :
• Any condition affect balance between
prothrombotic and antithrombotic effects of
endothelium .

Abnormal blood flow
:
a- turbulent blood flow
b- stasis

• turbulent blood flow is Important in arterial
and cardiac thrombus formation
• Mechanisms:
• Endothelial injury and dysfunction
• Forming countercurrents and local pockets
of stasis

Stasis:
• Promotes endothelial cell activation
• Allows` platelets and leukocytes to come into contact
with the endothelium
• Slows the washout of activated clotting factors
 Conditions associated with stasis:
• aneurysms
• Mitral valve stenosis (left atrial dilatation)
• Atrial fibrillation
• Hyperviscosity syndromes(e.g polycythaemia),sickle
cell disease

Hypercoagulability
:
• An important risk factor for venous
thrombosis
• Define as any alteration of the coagulation
pathway that predisposes affected persons
to thrombosis and can be divided into:
1- primary (genetic )
2- secondary(acquired)

1- primary(inherited) hypercoagulability:
• Factor V Leiden mutation
• prothrombin mutation(G20210A variant )
• Deficiency of anti-thrombin III. protein C,
protein S.
• ↑Homocysteine

2
-
secondary (acquired ) hypercoagulability
:
A- high risk for thrombosis
:
• Prolonged bed rest or immobilization
• MI
• Atrial fibrillation
• Cancer
• Prosthetic cardiac valve
• Disseminated intravascular coagulation
• Heparin induced thrombocytopenia
• Antiphospholipid antibody syndrome

B- low risk for thrombosis
:
• Cardiomyopathy
• Nephrotic syndrome
• Pregnancy and postpartum
• Oral contraceptive use
• Sickle cell anemia
• Smocking

Morphology
• Thrombi are focally attached from the
vascular surface
• Propagate toward the heart →
• Arterial thrombi grow in retrograde
direction
• Venous thrombi extend in the direction of
blood flow.

Non-occlusive thrombi in wall of atherosclerotic aorta

Occlusive thrombus in wall of
atherosclerotic coronary artery

• Thrombi have apparent laminations called
Lines of Zahn
• (Lines of Zahn only found in thrombi that
formed in flowing blood (distinguish ante
mortem thrombosis from blood clots that
formed in postmortem state)

Alternating layers of a) platelets and fibrin and b) red blood cells
a b

• Thrombi formed in heart chambers and
aortic lumen → mural thrombi
• Arterial thrombi are rich in platelets

Postmortem clots:
• Gelatinous
• Darker red dependent portion and a yellow
(chicken fat) upper portion
• Not attached to the underline vessel wall

• Thrombi on heart valves →vegetation
• Infective endocarditis
• Sterile vegetation
• Sterile verrucous endocarditis (Libman-Sacks-
endocarditis) →SLE

Fate of the thrombus
:
• Over days or weeks thrombus evolve
through the following processes:
1-Propagation
2-Embolization
3-Dissolution
4-Organization

Clinical significance of thrombi
:
1
-
obstruction of arteries and veins
(
mainly arterial
)
2
-
give rise to emboli (mainly venous)

Venous thrombosis:
Superficial or deep veins of the legs
A-Superficial veins thrombosis
occur mainly in the saphenous veins
B-Deep vein thrombosis
 (popliteal ,femoral and iliac veins)
 are prone to embolize
 Could be asymptomatic(50%) (collateral)
 Are associated with stasis and
hypercoagulable states .

Conditions associated with increased
risk of DVT:
• Trauma , surgery and burn
• Pregnancy and postpartum
• Tumors
• > 50 years
• Disseminated Intravascular Coagulation

Embolism
 An embolus is an intravascular solid ,
liquid , or gaseous mass that is
carried by the blood to a side distant
from its point of origin

 Most are derived from thrombus →
thromboembolism
Other types of emboli:
 fat droplets
 Bubbles of air
 Cholesterol emboli (atherosclerotic debris)
 Amniotic fluid
 Tumor fragment
 Bites of bone marrow

Consequences of emboli:
 Systemic embolization→ partial or
complete vascular occlusion→
ischemic necrosis (infraction)
 Pulmonary embolization →hypoxia ,
hypotension and right sided heart failure

Pulmonary Thromboembolism
:
 Incidence of PE in hospitalized
patients is 2-4/1000
 95% of cases arise from DVT in veins
proximal to the popliteal fossa
 Pass through progressively larger
channels →right side of the heart
→arrested in the pulmonary
vasculature

depending on the size PE can :
 1- occlude the main pulmonary artery
 2-lodge at the bifurcation of the right and
left pulmonary arteries (saddle embolus)
 3-Pass into the smaller arterioles
 Rarely → an embolus pass through an
arterial or ventricular defect → systemic
circulation →paradoxical embolism

 Small emboli→ clinically silent (60-80%)
 Large emboli → block pulmonary artery→
sudden death
 Medium → pulmonary haemorrhage
 Pulmonary infraction can occur in setting
of left cardiac failure (↓ bronchial artery
perfusion)
 Multiple emboli occurring over time
→pulmonary hypertension→ right
ventricular failure (cor pulmonale)

Systemic Thromboembolism
:
 80% arise from intracardiac mural thrombi
 2/3 associated with left ventricular infract
 25% associated with dilated left atria
others→
 Aortic aneurysms
 Thrombi overlying ulcerated atherosclerotic
plaques
 Fragmented valvular vegetation
 Paradoxical emboli
 10-15% are of unknown origin

common arterial embolization site
include:
 Lower extremities (75%)
 CNS (10%)
 Intestine , kidneys and spleen

Consequences of embolization depend
on:
 Calibre of the occluded vessels
 The collateral supply
 Vulnerability of the affected tissue to
hypoxia

Fat embolism :
 Crush injury
 Long bone fractures
 Occur in 90% of individuals of sever skeletal
injury but only 10% develop fat embolism
syndrome →
 Develops 1-3 days after injury
 Sudden onset of
tachypnea ,dyspnoea ,tachycardia ,irritability
which can progress rapidly to coma

Amniotic fluid embolism:
 Occurs during labor and immediate postpartum period
 It is due to entry of amniotic fluid into maternal
circulation
 Mortality rate = 80%
Characterised by sudden onset of sever:
 dyspnea
 Cyanosis
 Hypotensive shock
 If survive →typically the patient develops pulmonary
edema (in about half the patients + DIC)

Air embolism:
 Bypass surgery (coronary artery)
 Neurosurgery (cerebral artery)
 During obstetric procedures
 Chest wall injury
 Can arrest in heart and cause death

 Particular form of gas embolism is called
Decompression sickness
 Caused by sudden change in
atmospheric pressure
 It is a risk in:
 Scuba(Self-Contained Underwater Breathing
Apparatus) divers
 Underwater construction workers
 In an unpressurised aircraft

 When air is breathed under high
pressure → increased amount of gas
becomes dissolved in blood and tissues
→ depressurized → gas emboli →
tiusse ischemia
 Rapid formation of the gas bubbles in
skeletal muscles and around the joints→
painful condition called the bends
 In the lung cause pulmonary
edema ,haemorrhage and emphysema

 Chronic form of decompression
sickness is Caisson Disease →
recurrent gas emboli→ multifocal
ischemic necrosis

Infarction
• An infarct is an area of necrosis caused by
occlusion of vascular supply to the affected
tissue .
• Cardiac infarction
• Cerebral infarction
• Bowel infarction
• Gangrene

Cause of blood vessel occlusion
:
o Thrombosis or embolism
o Vasospasm
o Atheroma
o Compression(tumor)
o Edema within confined space
o Vessel twisting (bowel volvulus)
o Traumatic vascular rupture
o Entrapment in hernia sac
Venous thrombosis ( organ with single efferent vein e,g
ovary and testis)

Morphology
Infarcts are classify on the basis of:
1- their color
2-presence or absence of microbial
infections
 red (hemorrhagic) or white (anemic)
Septic or bland

Red infarcts:
 Occur in venous occlusions (ovarian torsion)
 Loose tissues (lung and other spongy organs )
 In tissues with dual circulation (intestine)
 On top of congestion
 On reperfusion
 Intracellular hemosidern

White infarcts:
• Occur with arterial occlusions in solid organs
• With end arterial circulation
• Heart , spleen, kidney
• Wedge-shaped (occluded vessel at the apex)
• The margins progressively become paler and
sharply defined

• The main histologic finding associated with
infarcts is coaculative necrosis
• Inflammatory response appears in the
margins within a few hours
• Well defined within 1-2 days
Brain → liquefactive necrosis

The outcome of vascular occlusion depends
on:
The anatomy of vascular supply
Rate of occlusion
Tissue vulnerability to ischemia (neurons 3-4
minutes, myocardial cells 20-30 minutes )
Hypoxemia

Thrombosis And Embolism of the general pathology

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