Thrombosis

It is the process of thrombus formation.

Thrombus

-It is a compact mass formed of the circulating blood elements within the cardiovascular system during life.

-Is a solid mass formed of blood elements inside the cardiovascular system during life

Predisposing factors for thrombosis:-

Three main factors (Virchow’s triad)

1- Endothelial damage (dysfunction).

2- Change in the pattern of blood flow (stasis or turbulence).

3- Changes in composition of blood ( blood coagulability).

Thrombus

Is a solid mass formed of blood elements inside the cardiovascular system during life

Predisposing factors for thrombosis:-

1) Endothelial damage (dysfunction)

2) Change in the pattern of blood flow (stasis or turbulence).

3- Changes in composition of blood ( blood coagulability).

Increased concentration of coagulation proteins or reduced concentration of natural anticoagulants. This change may be hereditary ,acquired or immune mediated

A- Hereditary:-

* About 5-10% of all people have some genetic defect predisposing them to thrombosis.

* These include congenital deficiency of antithrombin III, protein C and protein S and mutation in the gene encoding factor V.

B- Acquired :-

* Tissue damage….increase the production of thromboplastin and other procoagulants.

* Chronic infection…. Liver produces excess fibrinogen (one of acute phase reactants).

* Estrogen containing oral contraceptives….increase the production of prothrombin and fibrinogen.

*Tumors…..increased release of thromboplastin.

C- Immune mediated thrombosis

*Heparin-induced thrombocytopenia

-seen in 5% of patients with chronic use of high molecular weight heparin.

– Caused by antibodies to the complex of heparin and platelet factor 4 → Antibodies cross reacts with platelets and endothelial cells → platelet and endothelial injury → thrombosis.

Morphology of thrombi

Large thrombi formed in veins, arteries and heart of living patients have typical features that distinguish them from postmortem clots. These include

1- Lines of Zhan:-

Formed by deposition of platelets and fibrin, which form a white layer. RBCs deposit on this layer forming a red layer on which a new layer of fibrin and platelets is deposited. These alternating white and red lines are called lines of Zhan .

2- Friability :-

Thrombi are held together with fibrin that does not permeate all layers uniformly but leaves cleavage lines between the white and red layers. The friability of thrombi accounts for the fact that they may detach and embolize.

3- Attachment:-

Thrombi are attached to the surface of the vessel or heart chamber in which they arise.

4- Molding :-

Thrombi formed inside veins typically retain the shape of the vessel in which they originate. They fill and expand the affected vessel and its tributaries.

* Postmortem clots

They differ from thrombi in that

1- They form in stagnant (non-circulating) blood.

2- Red blood cells sediment and separate from plasma forming (red current jelly) the plasma above forms a yellow part (chicken fat). No lines of Zhan are formed.

3- They are not attached to the wall of blood vessel and can be washed easily from it.

4- They are soft and moist ( not friable).

5- They do not fill or expand the affected vessel.

Sites of thrombi

Thrombi that occur in different parts of the circulation have different causative factors and different macroscopic appearances

Venous thrombi “phlebothrombosis”

– Form in slow-moving blood.

– Have a high proportion of trapped red cells in relation to platelet/fibrin therefore they are red, soft gelatinous with poor lamination.

– They grow (propagate) towards the direction of the heart.

– They may detach to produce emboli

– Thrombi of infected veins are called thrombophlebitis. They are the source of infected emboli (pyemia).

– Almost all venous thrombi occlude the lumen and prevent blood flow…..Occlusive thrombi.

– Thrombi over cusps of the heart are called vegetations

Leg vein thrombosis

Conditions associated with an increased risk of thrombosis

1- Deep venous thrombosis of LL (DVT) less commonly superficial varicosities.

2- Massive tissue damage e.g. trauma , burns or major surgery are commonly associated with thrombosis. Increased blood coagulability and prolonged bed rest resulting in stasis are responsible factors.

3- Pregnancy and obstetric conditions, prolonged use of oral contraceptives, and steroid therapy.

4- Myocardial infarction, strokes and atherosclerosis.

5- Tumors…release thromboplastin….++ thrombosis.

* Outcome of thrombosis

1-Resolution:-

Fibrinolysis of the thrombus is  mediated by plasmin.Since the endothelium lining veins produce more plasminogen activator, venous thrombi are resolved more readily than arterial and cardiac thrombi.

2- Propagation:-

Due to deposition of more platelets, fibrin and RBCs. A tail is formed which is more liable for detachment and embolization.

– Propagation occurs more with venous thrombi and progress towards the direction of the heart.

3- Embolization:

Due to detachment of thrombi from vessel wall.

– Septic thrombi produce pyemia.

4- Organization

Ingrowth of granulation tissue from vessel wall into the thrombus. Later on it changes to fibrous tissue which may be incorporated into the vessel wall.

5- Recanalization

Blood vessels in the granulation tissue may fuse into larger channels that bridge the thrombus with partial restoration of the blood flow in the affected vessel.

Embolism

Definition

It is a detached intravascular solid, liquid or gaseous material that is carried by blood to a site distant from its point of origin to be impacted in a small blood vessel.

Types

1- 99% ..thrombo-embolism
2- Fat emboli
3- Parasitic emboli
4-Air or nitrogen emboli
5- Amniotic fluid emboli
6- Tumor emboli

Clinically most important emboli are:-

1- Venous emboli….originating mostly from thrombi of the leg veins and produce pulmonary embolism.

2- Arterial emboli….originating from the heart, aorta or large vessels and produce systemic embolism e.g. in the brain, kidney and spleen.

1) Pulmonary embolism

In 95% of cases they originate from thrombi of deep leg veins above the level of the knee.

Effects on the lung depend upon the size of the embolus and state of the lung:-

1- 60-80% of cases are small and clinically silent.

2 – 3 size of embolism

Large sized emboli

-obstruct the pulmonary bifurcation (saddle emboli) or one of main pulmonary arteries……sudden death (acute right sided failure) without manifestations of pulmonary infarction.

Medium sized emboli

– with normal lung have no effect  why?
– With lung congestion it produce pulmonary infarction.

Small repeated emboli

With time they produce pulmonary hypertension ending in right –sided heart failure (cor-pulmonale)

2) Fat emboli

Causes:-

-Fracture of long bones.
– Trauma or burn to fatty tissue.

Effects :-

– Mechanical obstruction.
– Chemical release of FFA… local toxic effects with injury to vascular endothelium and platelet adhesion.

3) Air embolism

Causes:-

1-Injury of jugular vein.

2- childbirth or abortion.

3- Blood transfusion under positive pressure.

Effects:-

– Small amounts…no effects

– More than 100 cc. → Fill the right side of the heart → acute heart failure → Death.