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
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
8.
9.
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.
12.
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.
15.
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
19.
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.
21.
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
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.
27.
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.
29.
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.
33.
34.
35.
36. Arterial Thrombi
Usually occlusive
Sites: Coronary, Cerebral, Femoral
Thrombus on atherosclerotic plaque or
sometimes vasculitis
Firmly adherent to injured endothelium
Gray-white, friable
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)
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
45.
46.
47.
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.
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