Thrombosis Definition: Formation of solid plug any where in intact cardiovascular system from constituents of blood during life.

1. Dr. Shubhangi Agale
Associate Professor
Grant Govt Medical
College, Mumbai.

2. Functions of Normal Hemostasis
Maintain blood in a fluid and clot free
state
Induce a rapid and localised
hemostatic plug at a site of vascular
injury
Hemostasis and thrombosis are
regulated by: the vascular wall,

3.  Normal flow of liquid blood is
maintained by following properties of
endothelial cells
Antiplatelet properties
Anticoagulant properties
Endothelium

4. Thrombosis
Definition:
Formation of solid
plug any where in
intact cardiovascular
system from
constituents of
blood during life.

5. Differential Diagnosis
1. Blood clot: A mass of coagulated blood
formed in vitro e.g. in a test tube.
2. Haematoma: Extra vascular accumulation
of blood clot e.g. into the tissues.
3. Haemostatic plug: Blood clots formed in
a healthy individual at the site of injury.

6. Effects of Thrombosis :
“ Life threatening”
1. Ischaemic injury: Thrombi may
decrease/ stop the blood supply to part of
an organ/ tissue and cause ischaemia which
may subsequently result in infarction.
2. Thromboembolism: The thrombus or
its part may get dislodged and be carried
along in the blood stream as embolus to
lodge in a distant vessel e.g. Pulmonary
embolism.

7. Pathogenesis
Three primary influences predispose to
thrombus formation (Virchow triad)
Endothelial injury
Stasis or turbulence of blood flow
Hypercoagulability of blood

10. 1. Endothelial Injury
1. Role of vessel wall.
2. Role of Platelets.
3. Role of coagulation system.
Role of vessel wall:-Integrity of vessel
wall is important to maintain normal
blood flow.

11. Endothelial Injury
Intact endothelium has following functions-
1. Protects the flowing blood from thrombogenic
influence of subendothelium.
2. Elaborates few anti thrombotic factors like
heparin like
substance,thrombomodulin,inhibitors of
platelet aggregation,fibrinolysis-TPA.
3. Release of prothrombotic factors-
Thromboplastin,von Willibrand’s factor,platelet
activating factor,inhibitor of TPA.

13. A leads to –
Exposure of subendothelium ( collagen,
elastin, fibronectin,laminin,
glycosaminoglycans)which are
Thrombogenic.
Brief vasoconstriction of small blood vessels
–to reduce the blood flow.
Major significance in arterial thrombi/in
heart.
Vasculr injury::

14. Conditions where vascular injury
predispose to formation of thrombi
Endocardial injury in myocardial
infarction, cardiac surgery, prosthetic
valves.
Ulcerated plaques in athrosclerosis.
Hypertension, Diabetis Mellitus,
cigarette smoking.
Arterial diseases.

16. Endothelial dysfunction without
endothelial loss
Hemodynamic stresses of Hypertension
Turbulent flow over scarred valves
Bacterial toxins
Homocystinuria
Hypercholesterolemia
Radiation
Products absorbed from cigarette smoke

17. 2. Alteration in Normal Blood Flow
Turbulence
a) Causes endothelial injury or dysfunction,
b) Forms counter currents and local pockets of
stasis
Stasis: Disrupts normal blood flow
Normal blood flow (Laminar): Platelets flow
centrally separated from the endothelium by
plasma

18. Stasis and Turbulence
Bring platelets into contact with endothelium
Prevent dilution of clotting factors
Retard inflow of clotting factor inhibitor and
permit the build-up of thrombi
Promote endothelial cell activation,
predisposing to local thrombosis

20. 2. Alteration of blood flow
Formation of arterial and cardiac thrombi is
facilitated by turbulence in the blood flow.
Stasis initiates the venous thrombi even without
evidence of endothelial injury.
In turbulence and stasis, the normal axial flow of
blood is disturbed so that the platelets come into
contact with the endothelium.
Inhibitors of coagulation fail to reach the site of
thrombus resulting in enlargement of the
thrombus site.

22. 3. Hypercoagulability
Any alteration of the coagulation
pathways that predisposes to
thrombosis.
A) Primary or Genetic.
1. Mutation in factor V gene (Leiden)
2. Mutation in Prothrombin gene.
3. Mutation in Methyltetrahydrofolate
gene.

23. 4. Rare
a) Antithrombin III deficiency
b) Protein C
c) Protein S deficiency
d) Fibrinolysis defects
Hypercoagulability

24. Hypercoagulability
Secondary (Acquired):
A) High risk:
1. Prolonged bed rest/immobilisation
2. Myocardial infarction,
3. Atrial fibrillation
4. Tissue damage
(surgery, fracture, burns, cancer)
5. Prosthetic cardiac valves,
6. DIC
7. Heparin induced thrombocytopenia
8. Antiphospholipid antibody syndrome

25. Gross appearance
Arterial thrombi-White, mural,
firm ,pale.
Venous thrombi- red, occlusive, soft,
gelatinous.
Mixed or laminated- Alternate red &
white layers –Lines of Zahn.

26. Types of thrombi
Antemortem Thrombi.
1. Gross-
Dry,granular,firm,friab
le
2. Adherant to vessel
wall.
3. Shape- May or may
not fit their vascular
contours.
4. Surface contains
apparent lines of
Zahn.
Postmortem clots.
1. Gross-Gelatinous,
soft, rubbery.
2. Weakly attached.
3. Take the shape of
vessel or its
bifurcation.
4. The surface is chicken
fat yellow covering
the underlying red
currant jelly.

28. Microscopy
Composition depends upon rate of flow of
blood.
Lines of Zahn are formed by light staining
aggregated platelets admixed with fibrin
and dark staining layer of red cells.
Red thrombi have more abundant red cells
leucocytes & platelets entrapped in fibrin
meshwork.

30. Sites for Thrombi
Any where in cardiovascular system
Variable in size and shape
Arterial: at ulcerated Atherosclerotic plaque
Cardiac: MIAuricular appendage, Stenotic valve
Vessel bifurcation due to turbulence
Venous thrombi: At site of stasis
Firmly attached at the point of origin
Arterial: Thrombi grow retrograde
Venous: Thrombi extend towards heart

31. Mitral valve stenosis
Atrial fibrillation
Stasis due to hyperviscosity syndrome
(Polycythemia)
Deformed red cells (Sickle cell anemia)
Clinical settings contributing to
thrombosis

32. Cardiac Thrombi
Vegetations of infective endocarditis.
Maccallum patch in RHD.
Myocardial infarction-subendocardial.
Ball valve thrombus.
Atrial appendages.

36. Arterial Thrombi
Usually occlusive
Sites: Coronary, Cerebral, Femoral
Thrombus on atherosclerotic plaque or
sometimes vasculitis
Firmly adherent to injured endothelium
Gray-white, friable

37. Arterial thrombi
Aorta:aneurysms,arteritis.
Coronary arteries:atherosclerosis.
Mesentric artery:atherosclerosis,arteritis.
Arteries of limbs:atherosclerosis,diabetes
mellitus, Buerger’s disease, Raynaud’s
disease.
Renal artery: atherosclerosis,arteritis.
Cerebral artery:atherosclerosis,vasculitis.

41. Venous thrombi
Veins of lower limbs:deep veins of legs,varicose
veins.
Popliteal,femoral and iliac veins:postoperative
stage,postpartum.
Pulmonary veins:CHF,pulmonary hypertension
Hepatic and portal vein:portal hypertension
Superior vena cava:infections in head and neck
Mesentric veins:volvulus,intestinal obstruction

42. Arterial vs Venous Thrombus
Grossly: Thrombi are friable, a mixture of red and
gray in irregular layers, dull, and attached to the
endothelium
Arterial thrombus: Dry, friable gray masses
composed of almost regularly arranged layers of
platelets and fibrin, irregularly mixed with small
amounts of darker red coagulated blood (White or
conglutination thrombus)
Venous thrombus: Red, gelatinous
(Stasis or red coagulation thrombus)

43. Capillary Thrombi
Vasculitis.
Acute inflammatory lesions.
Disseminated intravascular
coagulation.

44. Fate of Thrombus
Propagation: May accumulate more
platelet and fibrin leading to fibrosis
and inflammation
Recanalisation: Reestablish vascular
obstruction
Embolisation: Thrombi may dislodge
Dissolution: Removed by fibrinolytic
activity
Organisation: Thrombi may induce
flow

48. Predisposing Factors
Primary(Genetic)factors:
1. Defficiency of antithrombin,Protien C / S.
2. Defects in fibrinolysis.
3. Mutation in Factor V.
Secondary (acquired) factors:
1. Prolonged bed rest / Immobilisation.
2. Use of oral contraceptives.
3. Cigarette smoking.
4. Tissue damage: trauma,fractures,burns.

49. 1. Heart diseases- MI, CHF, RHD,
Cardiomyopathy.
2. Atherosclerosis.
3. Aneurysms of Aorta.
4. Varicose veins.
5. Nephrotic syndrome.
6. Dissseminated cancers.
Clinical conditions predisposing
to thrombosis

50. Clinical Effects of Thrombosis
Cardiac thrombi- sudden death,
thromboembolism
Arterial thrombi- sudden death,
thrombosis of coronary artery
Venous thrombi-thromboembolism, skin,
thrombophlebitis,
Capillary thrombi- DIC

51. Clinical Correlation
Arterial Thrombi: Obstruction of coronary
arteries (Myocardial infarction), cerebral,
Renal arteries, and arteries of spleen
Venous Thrombi: Congestion and ed
ema distal to obstruction, may embolise to
lung (Pulmonary embolism) causing death
Superficial venous Thrombi: Congestion,
swelling, pain, tenderness (rarely embolise)

52. Clinical Correlation
Deep Venous Thrombi: (Popliteal, femoral,
Iliac)
Occurs in cardiac failure due to stasis
Immobalisation
Release of procoagulant substances from
tissues: Puerperium, Amniotic fluid infusion
into circulation in delivery
Hypercoagulability: late pregnancy, Postpartum
period
Release of tumor associated procoagulant

53. SUMMARY
Definition
Effects of thrombi
Pathogenesis
Virchow’s triad
Antemortem / postmortem thrombi
Gross appearance
Microscopy
Types of thrombi
Fate of thrombus
Predisposing Factors
Clinical Effects of Thrombosis