Hemostasis and Thrombosis:

Hemostasis is a normal physiologic process. It maintains blood in fluid condition and

clot-free state in normal vessels by inducing a rapid and localized hemostatic plug at
sites of vascular injury.

Thrombosis represents a pathologic state in which there is formation of intra-vascular

solid mass (thrombus) from the elements of circulating blood. The vessel may be
uninjured or with minor injury.

Thrombosis:
Three primary factors influence thrombus formation (Virchow’s triad):

1. Endothelial injury.

2. Slowing of blood flow.

3. Hyper coagulability of blood.

1. Endothelial injury commonest cause, mainly in the heart and arterial circulation
(e.g. myocardial infarction, endocarditis, ulcerated atherosclerosis). Injury may occur
from diverse causes e.g. hemodynamic stress (hypertension or turbulent flow in
aneurysms), radiation, products absorbed from cigarette smoke, extensive burn etc.

2. Slowing of circulation (alteration in normal blood flow):

Normal blood flow is laminar (i.e., the cellular elements flow centrally inside the
vessel, separated from endothelium by a clear zone of plasma).

Stasis and turbulence disrupt laminar flow and bring platelets into contact with the
endothelium.

They prevent dilution of activated clotting factors by fresh flowing blood, retard the
inflow of clotting factor inhibitors and permit the build-up of thrombi.

Stasis is important in causing thrombosis in veins, cardiac chambers and arterial

aneurysms.

Hyper viscosity syndrome - Example: In polycythemia or deformed RBC as in sickle

cell anemia causes stasis in small blood vessels predisposing to thrombosis.

3. Hypercoagulability of blood may be due to heritable gene mutation or acquired.

Example: Severe burn, shock, oral contraceptive, increased hepatic synthesis of

coagulation factors and reduced synthesis of anti-thrombin III.

Mechanism:
Normally, in a blood vessel, cellular elements flow centrally, forming axial stream
separated from endothelium by a clear, cell-free, plasmatic zone. Due to slowing of
the circulation, platelets come in contact with endothelium and are activated to
liberate tissue factors. Tissue factors recruit more platelets, which are deposited in
the form of ridges at right angles to the blood flow forming corrugations, known as
line of Zahn. Coming in contact with sub-endothelial collagen, platelets are activated
to release ADP, Thromboxanes etc. ADP aggregate more platelets.

Thromboplastin, liberated from platelets and injured endothelium initiate

precipitation of fibrin on the surface of platelets. Fibrin network may entangle RBC
and leucocytes.

A thrombus is thus formed, on the basis of platelets and fibrin, with varying number of
RBC and leucocytes.

Thrombi may form anywhere in the cardiovascular system.

Aortic and cardiac thrombi are typically nonocclusive (mural) as a result of rapid and
high-volume flow.

Smaller arterial thrombi may be occlusive.

All these thrombi usually begin at sites of endothelial injury (e.g. atherosclerotic
plaque) or turbulence (vessel bifurcation).

Venous thrombi characteristically occur in sites of stasis and are occlusive.

At sites of origin, thrombi are generally firmly attached. Arterial thrombi tend to
extend retrograde from the attached point; where as venous thrombi extend on the
direction of blood flow. The propagating tail may not be well attached and may
fragment to create an embolus.

Sites of thrombus formation:

Cardiac and arterial thrombi are formed slowly in rapid circulation. They are pale-gray
and tend to have gross and microscopic lamination (lines of Zahn) produced by pale
layers of plates and fibrin alternating with darker red cell-rich layers. These are
mostly seen in the left ventricle overlying an infarct, ruptured atherosclerotic
plaques, and aneurysmal sacs.

Venous thrombosis (phlebothrombosis) often created a long red-blue cast of the vein
lumen as it occurs in a relatively slow circulation. The thrombus contains more
enmeshed erythrocytes among sparse fibrin strands (red or stasis thrombus).

Fibrin and attachment to the vessel wall distinguish stasis thrombus from
postmortem clot. Phlebothrombosis is most commonly (more than 90 %) seen in the
veins of the lower extremities.
Thrombi may also form on heart valves. In infective endocarditis, bacteria or fungi
form large infected thrombi (vegetations), causing underlying valve damage and
systemic infection. Sterile vegetations (nonbacterial thrombotic endocarditis) can
also develop on noninfected valves in patients with hypercoagulable states,
particularly in those with disseminated cancer. Noninfective, verrucous(Libman-
Sacks) endocarditis is seen in patients of SLE due to circulating immune complex.

Heart:

i) Ball thrombus is seen in left atrium in mitral stenosis. It is large and spherical.

ii) Mural thrombus is seen over the wall of heart in cardiac infarct, cardiomyopathy

iii) Agonal thrombus is seen in right ventricle in case of death due to pneumonia.

iv) Vegetations over the cardiac valves are seen in endocarditis.

Artery:

i) On the atheromatous patch in coronary, cerebral, spleen, and renal arteries.

ii) Laminated thrombus is seen in aneurysmal sac.

iii) Marasmic thrombus is seen in marasmic children, in mesenteric artery (stasis)

Vein:

Veins are the commonest sites of thrombus formation due to slow circulation.

Other causes of venous thrombosis are:

i) Trauma, burn, due to reduced physical activity, injury to vessels and release of pro-
coagulants from tissue.

ii) Puerperal and postpartum thrombosis occurs mainly due to amniotic fluid infusion
into blood and hypercoagulability in late pregnancy and in postpartum period. .

iii) Disseminated cancer, due to release of tumour-associated -procoagulants.

iv) Advanced age, bed rest, immobilization, reduced physical activity diminishes
milking action of muscle.

v) Thrombophlebitis is the inflammation of the venous wall due to septic thrombus.

Example: a) Pelvic veins in puerperal sepsis ; b) Portal vein in acute appendicitis ; c)

Cavernous sinus in facial infection

Fate of a thrombus:

Septic thrombus causes abscess formation.

Aseptic thrombus may show:

i) Propagation causing complete vessel obstruction.

ii) Dissolution by fibrinolytic action.

iii) Detachment- with embolism.

iv) Organization and recanalization, re-establishing vascular flow by in-growth of

endothelial cells, smooth muscle cells and fibroblasts to create through-and through
capillary channels or by incorporating the thrombus as a sub-endothelial swelling of
the vessel wall.

Effect of thrombosis:

Septic: Forms abscess and may cause pyaemia.

Aseptic: Effect will depend upon the vessel involved and efficiency of the collateral
circulation of the area.

1. Arterial thrombus - in a small vessel is occlusive and usually causes infarction. This
is particularly seen when it involves organs supplied with end-arteries (Example:
cerebral, coronary, splenic, mesenteric and renal arteries).

2. Venous thrombosis - rarely causes infarction, as collateral channels soon enlarge to

maintain the venous drainage.

Superficial venous thrombosis, as in varicose saphenous veins, causes local edema

and impaired venous drainage, predisposing to skin infection and varicose ulcer.

Deep thrombi in larger leg veins above the knee (Example: popliteal, femoral and
iliac veins), have good collateral circulation but commonly embolize (about 50 %
cases).

Occlusive venous thrombi with poor collateral channels cause increased venous and
capillary pressure forming edema (Example: ascites in portal vein thrombosis).

Beneficial effect of thrombosis:

Thrombosis causes hemostasis and sealing of the vessel wall after erosion by
malignant tumours and attempts to prevent hematogenous spread.

Blood clot: Coagulation of dead blood (Example: in a test tube, in a blood vessel
after death or after ligature).

Types of clot:

1. Current jelly clot (soft and red) forms rapidly in great vessels or heart. All the
elements of blood are involved.
2. Chicken fat clot (lower part dark, upper part yellow) forms slowly, RBC settles at
the bottom and pale upper part consists of leucocytes and fibrin.

thrombus- intravascular, has platelets, fibrin, RBC, WBC- Lines of Zahn.

Blood clot: could be intra or extravascular, usually a post-mortem finding. It LACKS

platelets, and therefore no lines of zahn. not sure why no platelets.

thrombi are firm and friable because they are formed in layers
due to flowing blood, while blood clots tend to be more disorganized
since they form in environments deficient in certain necessary
elements (such as static blood or outside the vascular system).