Thrombus and Clot

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.

Hyperviscosity 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.