►1.

Robbins pathologic Basis of Diseases –

2000
►Pathology of Eye – GOH Naumann
►Ocular Pathology – 5th Edition
►Muir’s Textbook of Pathology
►Internet

Thrombosis Embolism
► Hemostasis – Basic concepts
► Thrombosis
 Predisposing Factors
 Basic terminologies
 Morphology & Fate of Thrombi
► Embolism
 Introduction ; Terms & Terminologies
 Major Types
► Clinical Correlation to Eye
 Retinal Vein Occlusion
 Types of Embolization
Thrombosis Embolism
 Hemostasis
►Hemostasis is a balance of two opposing
forces: clot formation and dissolution

►Major factors involved in Hemostasis:

 Platelets, Vascular endothelium, Coagulation

Process – Deposition of Fibrin

 Plasmin / Fibrinolytic system – Digests Fibrin

Thrombosis Embolism
The 3 categories are:
( to make the study easy)

 Primary hemostasis
 Secondary hemostasis
 Tertiary Hemostasis

Thrombosis Embolism
►Primary hemostasis: This is defined as the
formation of the platelet plug.
 Inhibitors
 Natural prostacyclin and nitric oxide, which are
released by endothelial cells, and bradykinin.
 Acquired: Aspirin

►Secondary hemostasis: formation of fibrin

through the coagulation cascade.
 Inhibitors: Natural : Antithrombin III
 AT binding to thrombin – enhanced by heparin
Thrombosis Embolism

(Used to prevent thrombosis)

►Tertiary hemostasis: This is defined as the
formation of plasmin for breakdown of the
clot.
 Drugs that inhibit fibrinolysis include
epsilonaminocaproic acid and tranexamic acid

Thrombosis Embolism
Series of overlapping processes after
the damage of a blood vessel:
► 1. Vasoconstriction
 Platelets adhere to the damaged wall.
 Release Serotonin
 Thromboxanes

► 2.Platelet plug formation

 Release of ADP
 Positive feedback mechanism
 Temporary seal

► 3.Coagulation
 Positive feedback mechanism
 Mesh of fibrin – strong
 Formation of ProthrombinThraoamcbtotsiiivsaEmtoboorlrismbyextrinsic and intrinsic
pathway
 Blood clotting factors:
I Fibrinogen
II Prothrombin
III Tissue factor
( Thromboplastin)
IV Calcium (Ca++)
V Labile Factor ► B. .:

VII Stable factor  There is no factor VI

VIII.Antihaemophilic globulin  Vit. K is essential for
(A. H. factor A) the synthesis of
factors : ii vii ix & x
IX. Christmas factor
 Their no.s represent
(A.H. factor B) the order in which
X.Stuart Power factor they were
XI A.H. factor C discovered.
XII.Hageman factor
XIII.Fibrin Stabilising FactoThrrombosis Embolism
He
Hemostasi
is
► 4. Fibrinolysis

 Removing blood and healing damaged blood vessels

Activators

Plasminogen Plasmin

Fibrin Breakdown products

Thrombosis Embolism
 Control Of Coagulation:

► 1. Perfect smoothness of blood vessel lining

► 2. Presence of natural anticoagulants like Heparin

► 3.Binding to Thrombin to a special thrombin

receptor on the cells lining blood vessels.

Thrombosis Embolism
► Thrombus:
Thrombosis
an aggregation of
blood factors primarily
platelets & fibrin with
entrapment of cellular
elements, frequently causing
vascular obstruction at the
point of its formation

► Thrombosis : Formation of a
solid or a semisolid mass from
the constituents of the blood
within the vascular system
within life.
Thrombosis Em bolism
 Thrombosis

► Pathogenesis

 Primary influences
predisposing to
thrombosis

Thrombosis Embolism
 Endothelial Injury
► Dominant influence

► Any perturbation in the

dynamic balance of the
pro and antithrombotic
effects of the
endothelium can
influence local clotting
effects

Thrombosis Embolism
► Endothelial dysfunction d/t hemodynamic stresses
of hypertension, turbulent flow over scarred
valves, or bacterial endotoxins

► Homocystinuria, Hypercholesterolemia, radiation

or products absorbed from cigarette smoke may
initiate endothelial injury.

► Thrombosis in cardiac chambers, over ulcerated

plaques in atherosclerotic arteries or at traumatic
or inflammatory vascular injury - largely d/t
endothelial injury.
Thrombosis Embolism
 Endothelial Enjury

► Exposure of subendothelial proteins

► Platelets adhesion
► Prevention from blood loss Thrombosis Embolism
Excessive adhesion of platelets - Blockage
Thrombosis Embolism
 Alterations in Normal Blood Flow
( Turbulence & Stasis)
► Turbulence
 Arterial & cardiac thrombosis
- endothelial injury or dysfunction

► Stasis and Turbulence

1. Disrupt laminar flow – Platelets into contact with the
endothelium
2. Prevent the dilution of activated clotting factors
3. Retard the inflow of clotting Factor inhibitors
4. Promote endothelial cell activation
Thrombosis Embolism
 Contribution of Turbulence & Stasis to
Thrombosis in Clinical Settings:
► Ulcerated atherosclerotic plaques – sources of turbulence
► Abnormal aortic and arterial dilations (Aneurysms) –
Favored sites of Thrombosis

► Myocardial Infarction - regions of non-contractile

myocardium – stasis
: Mural Thrombi
► Mitral valve stenosis – Left arterial dilation

► Hyper-viscosity syndromes cause small vessel stasis

and in sickle cell anemia deformed RBCs cause vascular
occlusions

Thrombosis Embolism
 Hypercoagulability
► Lesscontribution to thrombosis
► Causes :
► Primary
(Genetic)
►Secondary (Acquired)

► Inherited causes of Hypercoagulability

 Mutations in the factor v gene and Prothrombin
 Polymorphisms
 Inherited deficiency of anticoagulants such as
Antithrombin III, Protein C or protein S

Thrombosis Embolism
 Significances of inherited disorders:
►Individually uncommon

►1. Mutations are usually co-inherited

►( a and b together ) > ( a + b)

►2.Higherrisk of developing venous

thrombosis

Thrombosis Embolism
 Acquired Thrombotic Diatheses
►More complicated and multifactorial

►Causes:
 Stasis or venous injury
 Increased hepatic secretion of many coagulation
factors and reduced synthesis of antithrombin
III
 Release of procoagulant tumour

Thrombosis Embolism
 Hypercoagulability seen with
advancing age:

►Due to Increased susceptibility to platelet

aggregation

►Smoking and obesity promote

hypercoagulability by unknown mechanisms.

Thrombosis Embolism
 Thrombosis
► Basic Terms and Terminologies:
► Agonal Thrombus : Clot formed in the Heart during the
process of dying
► Antemortem Thrombus
► Ball Thrombus
► Milk Thrombus
► Parietal Thrombus
► Fibrin Thrombus
► Hyaline Thrombus
► Infective Thrombus
► Primary Thrombus
► Stratified Thrombus
► Traumatic Thrombus

Thrombosis Embolism
Retinal branched vein Thrombosis

Thrombosis Embolism
 ► Laminated Thrombus/
mixed Thrombus

Coral Thrombus ► Mural Thrombus

Organized Thrombus

Thrombosis Embolism
 ► White Thrombus

► Annular Thrombus
► CalcifiedThrombus/ ► Blood plate / Platelet
Phlebolith Thrombus

Thrombosis Embolism
 Deep Vein Thrombosis
► formation of a blood
clot in a deep vein.

► Itcommonly affects
the leg veins, such as
the femoral vein or the
popliteal vein or the
deep veins of the
pelvis.

Thrombosis Embolism
 Deep Vein Thrombosis
► SIGNS AND SYMPTOMS
 pain,
 swelling
 redness of the leg and
dilatation of the surface
veins

► THERAPY
 Anticoagulation is the usual
treatment

Thrombosis Embolism
 PORTAL VEIN THROMBOSIS
►a form of
venous
thrombosis
affecting the
portal vein,
which can lead
to portal
hypertension
and reduction in
the blood supply
to the liver. Thrombosis Embolism
► Causes
 pancreatitis, cirrhosis,

►Treatments
 anticoagulants, shunts, bypass surgery, and
transplants.

Thrombosis Embolism
HEPATIC VEIN THROMBOSIS
-Occlusion of hepatic vein

Thrombosis Embolism
►Symptoms:
 progressive abdominal pain
 hepatomegaly , and later the symptoms of
hepatic dysfunction

►Therapy:
 anticoagulant medication
Thrombosis Embolism
 RENAL VEIN THROMBOSIS
► formation of a clot or
thrombus obstructing
the renal vein, leading
to a reduction in
drainage of the kidney.
► can lead to imbalances
in blood clotting factor

► Symptoms
 blood in urine
Thrombosis Embolism
 General Morphology / Characteristics of Arterial &
venous Thrombi
 Characteristics Arterial/
Cardiac Venous/Red/Stasis/
Thrombus Phlebo-thrombus
 Location At the site of At the sites of
endothelial injury or Stasis
turbulence
 Direction Retrograde dir. From In a directon of
pt. of attchment blood flow

 Nature  Usually Occlusive Almost invariably

occlusive
Gray – white,Firmly Red/stasis
adhered to arterial wall thrombus
Thrombosis Embolism
 Composed Tangled mesh of More enmeshed
of: platelets, fibrin, erythrocytes
erythrocytes &
degenerating
leucocytes

Common Coronory Arteries Veins of

sites Cerebral arteries Lower extremities
(In descending Femoral arteries upper extremities
order) Less common:
Periprostatic plexus
Ovarian and Peri uterine
veins

Thrombosis Embolism
 At Autopsy, post mortem clots may be
confused for venous thrombi:

Post Mortem Clots Red Thrombi

Gelatinous; red cells
settled by gravity
Not attached to the
underlying wall
More enmeshed
erythrocytes, under
transection reveal vague
strands of pale gray fibrin
Firmer, almost always
have a point of
attachment

Thrombosis Embolism
 Fate of Thrombus :
► 1. Propagation
– Accumulation of more platelets and fibrin;
vessel obstruction

► 2. Embolization
– Dislodge and travel to other sites

► 3. Dissolution – Removed by fibrinolytic activity

► 4. Organization and recanalization

- May induce inflammation and fibrosis
- Re-establish vascular flow
Thrombosis Embolism
 Lab Tests to measure Coagulation and
Thrombolysis
► Platelet count
► Bleeding time
► APTT (Activated Partial Thromboplastin Time)
 Measure of intrinsic pathway
 Used to monitor Heparin Therapy

► Prothrombin Time – Used to measure

effectiveness of oral anticoagulants like warfarin
► Thrombin Time
► Fibrin Clot Stability
► Measurement of Fibrin degradation Products

Thrombosis Embolism
 Embolism
► Embolus:
detached intravascular
solid liquid or gaseous
mass that is carried by the
blood to a site distant
from its point of origin

► Unless otherwise
considered – thrombotic
in origin
► Results in partial or
complete vascular
occlusion

► Potential consequence - Thrombosis Embolism

Infarction
Thrombosis Embolism
 Terms and Terminologies
► Thromboembolism
► Pulmonary embolism
► Air embolism – after trauma or surgical procedures
► Amniotic Fluid Embolism
► Fat / Oil embolism
► Coronary embolism – of coronary arteries
► Crossed / Paradoxical Embolism
► Direct embolism – in the direction of the blood flow
► Bland embolism – when thrombotic plug is composed of
non-septic material
► Bacillary embolism – By aggregation of bacilli.
► Bone marrow embolism : By material from a fractured
bone
► Capillary Embolism – Blockage of capillaries with bacteria
Thrombosis Embolism
► Retinal Embolism – ► Pulmonary embolism
Central artery of the
retina

Thrombosis Embolism
Cerebral embolism- Of a cerebral artery

Thrombosis Embolism
 Thromboembolism
► A) Pulmonary thromboembolism

 Incidence : 20 – 25 / 100,000
hospitalized patients
►In 95 % instances, - venous
emboli
 Multiple Emboli : Pts. Who had
once – high risk of having
more.

 60 to 80 % pulmonary emboli
are silent – small
 When > 60 % pulmonary
circulation is obstructed with
emboli, - Right Heart Failure
Thrombosis Embolism
 # Effects:
 Depends upon size
 May occlude main pulmonary
artery, impact across the
bifurcation (Saddle
embolus ) or pass out into
smaller branching arterioles

Embolic Obstruction of :
► Medium sized artery:
 Pulmonary haemorrhage
► Small End-arteriolar pulmonary
branches:
 Infarction
► Multiple Emboli :
 Pulmonary hypertension
with right heart failure
Thrombosis Embolism
 Systemic Thromboembolism
= within the arterial circulation
► 80% arise from intracardiac mural
Thrombi

► Major sites :
 Lower extremities (75%)
 Brain (10%)
► Consequences:
 Depends upon:
►Extent of collatoral vascular
supply in the affected tissue.
►Tissue’s vulnerability to ischemia
►Caliber of the vessel occluded.
► In General
►Infarction to tissues downstream
of the obstructed veTshrsomebolsis Embolism
 Fat Embolism
► Fat released by marrow or
adipose tissue injury
► 90% with severe skeletal
injuries
► Fat Embiolism Syndrome:
 Pulmonary insufficiency,
neurologic symptoms, anemia
and thrombocytopenia
 Symptoms:
► Tachycardia Dyspnea
► Neurological Symptoms:
 Irritaqbility & restlessness
 Delirium to coma
► Pathogenesis
 Mechanical obstruction and
biochemical injury

Thrombosis Embolism
Air Embolism

► Can obstruct vascular flow

– Distal ischemic Injury

► Entrance
 During Obstetric procedures
 As a consequence of chest
wall injury ( Usu. In excess of
100 cc – clinical effect)

Thrombosis Embolism
► Decompression Sickness
 Exposition to sudden
changes in atmospheric
pressure
 People at risk:
► Deep sea divers, in
unpressurized aircraft in
rapid descent (??)

► Bends
 Rapid formation of gas
bubbles with in the
skeletal muscle &
supporting tissues.
Thrombosis E mbolism
► Effects:
 May induce local ischemia in brain, Heart etc.
 oedema in lungs leading to respiratory distress –
Chokes
 Haemorrhages and focal atelectasis or emphysema
► Treatment:
 Place the individual in compression chamber ( ??? )

► Caisson Disease
 More chronic form of decompression sickness
 Persistence of gas emboli in the skeletal system leads to
multiple foci of ischemic necrosis
 Common sites:
► Heads of Femur, Tibia and Humeri

Thrombosis Embolism
 Amniotic Fluid Embolism
► Grave but uncommon
complication of labor &
immediate postpartum
period

► Underlying Cause :
 Infusion of amniotic fluid or
fetal tissue into maternal
circulation through a tear in
the placental membranes or
rupture of uterine veins
Thrombosis Embolism
►Mortality
rate 20 – 40%
►Not managed well

►Onset characterized by
sudden severe dyspnea,
cyanosis & hypotensive
shock followed by
Seizures and coma

►Marked pulmonary
edema
►Diffuse alveolar damage
►Systemic fibrin thrombi

Thrombosis Embolism
Thrombosis Embolism
 Thrombosis & Embolism

►Most common causes of Occlusive Disorders

of Retina

 May arise from large vessels of neck or may be

cardiac in origin

 Common in pt.s with Hypertension & other

cardiovascular diseases
Thrombosis Embolism
 Retinal Artery Occlusion
► Usu. Unilateral
► CRAO – Obstruction at Lamina Cribrosa
BRAO – Lodgement of embolus at bifurcation

► Management
 Rx : Unsatisfactory
 Immediate lowering of IOP by IV mannitol &
intermittent ocular massage
 Anticoagulants

Thrombosis Embolism
 Retinal Vein Occlusion
► More common than artery occlusion
► CRVO – Non Ischemic ( Venous stasis retinopathy)-75%
►Mildto moderate vision loss
- Ischemic (Hemorrhagic retinopathy)
►Acute complete occlusion of central retinal
vein; marked sudden visual loss
►Treatment : Panretinal Photocoagulation

► BRVO – More Common Than CRVO

 Vision – affected only when macular area is involved
►Treatment : Grid retinal Photocoagulation

Thrombosis Embolism
► Retinal Vein Thrombosis - central retinal vein elderly; with
Glaucoma, Diabetes Mellitus, and Hypertension.

► Symptom: Painless visual loss

► Examination:
 the retinal veins appear distended and tortuous,
 the fundus of the eye appears congested and swollen,
 numerous hemorrhagic areas may be seen on the retina .
 neo-vascularization
 secondary (neovascular) Glaucoma can occur weeks after the occlusion.

► Tests : fluorescein Angiography

► Procedures (such as photocoagulation to remove new vessels

formed) can prevent seconThd
roma
bor
siy nboelisom vascular Glaucoma.
s Em
 Embolization In Eye
► Microemboli are frequent
causes of retinal arterial
emboli
► Sometimes
ophthalmoscopically visible
and may provide a clue to
the diagnosis of the
underlying disease

► Types of Emboli
 1. Calcium Emboli
 2. Cholesterol Emboli
 .....

Thrombosis Embolism
 1. Calcium Emboli
► Most commonly arise from the excrescences on
heart valves affected with rheumatic heart disease
or derived from calcified atheromatous plaques
► Frequently seen after heart and vascular surgery

► Can be recognized as white foci within the arterial

channels most commonly in the major branches
near the optic nerve
► Calcific emboli within the central artery:
 Not visible ophthalmoscopically
 Visible histopathologically
Thrombosis Embolism
 2. Cholesterol Emboli
 From atheromatous plaques of
the carotid artery system

 In the ocular Fundus – Visible

ophthalmoscopically; multiple
yellow shining flecks within
retinal arterioles, particularly
concentrated at bifurcations

 Dislodgement further into retinal

periphery – Frequent

Thrombosis Embolism
 3. Fat Emboli
►Fat emboli usually occur after fracture of
long bones.

►Indirect Traumatic Retinopathy

 An episode of ischemic micro infarction of the
retina with cotton wool spots, retinal edema and
hemorrhages

 d/t embolization of multiple fragments of bone

marrow fat into the central and peripheral
branches of the central retinal artery
Thrombosis Embolism
 4. Thrombocyte – Fibrin emboli

►Gray
►Difficultto see ophthalmoscopically
►After myocardial infarction or open heart
surgical procedures

Thrombosis Embolism
 5. Myxoma Emboli
► Histopathologically :- Star
shaped tumor cells embedded
within the mucoid matrix causing
occlusion of the vascular lumen
► Should be suspected in young
patients who suffer from multiple
retinal arterial occlusions

► In young patients; after

myocarditis, it is the commonest
cause of multiple ischemic
infarction
► Mistaken for retinal vascThuromlibtosisis Embolism
 Bacterial & Mycotic Emboli:
► Bacterial
 Have become rare
 Causes : Endocarditis, Septicemia
 Pathognomic Sign : Roth Spot
 Histopathologically, the lesions consist of perivascular
accumulation of leucocytes with in surrounding areas of
hemorrhages

► Mycotic – also rare

 Complication of long standing intravenous therapy and
in immunocompromised patients.
Thrombosis Embolism
 Experimental and Iatrogenic Emboli
► Experimental
 Using Latex or Glass spheres
 Injection of air or fibrin
► Iatrogenic
 By tiny metallic foreign bodies derived from heart-lung
machines
 Have been discovered in the retinal capillary tree
 Small particulate micro emboli have also been reported
after injection of crystalline corticosteroids locally

Thrombosis Embolism
 In brief…
► Emboli in the visual system can cause
 amaurosis fugax;
 visual field defects,
 cranial nerve palsies,
 central or branched retinal vessel occlusion,
 hypotensive retinopathy (Venous stasis retinopathy)
 narrowed retinal arterioles,
 neovascularization of the iris, optic disc or neural retina
 & the ocular ischemic syndrome

Thrombosis Embolism