THROMBOSIS, EMBOLISM, ISCHEMIA AND INFARCTION
Now that you have an understanding of normal hemostasis we will discuss diseased states as a result of abnormal hemostasis, and obstruction of blood flow: namely, thrombosis, embolism, ischemia and infarction.
THROMBOSIS

Thrombosis is the abnormal formation of a blood clot within the vasculature of a living animal. There are 3 major causes for thrombosis:

(1) endothelial damage

(2) alterations in normal blood flow

(3) hyper-coagulability of the blood.

Thrombosis can result from any one or any combination of the above.

Endothelial Damage
Remember from the unit on hemostasis that the endothelial cells have several anti-thrombotic properties. For example, endothelial cells secrete PGI2 which inhibits platelet aggregation. Endothelial release of nitric oxide causes vasodilation and inhibits platelet adhesion and aggregation. Also, endothelial cells elaborate protein C and endothelial surfaces are covered with heparin-like molecules that promote the activity of anti-thrombin III.
The triangle here is referred to as Virchow's triad. You don't have to remember that. But you do have to remember that any time there is a thrombus, it has to be ONE (or more) of the THREE parts of the triad. So, please, guarantee yourself some points on the exam and some acumen in the clinic by always thinking of these three causes when there is a thrombus present.
In addition to the anti-thrombotic activities of endothelial cells, damage can result in release of tissue thromboplastin (also known as tissue factor) and exposure of the sub-endothelial vascular collagen to platelets and clotting factors. During inflammation, cytokines (ie. IL-1 and TNF-alpha), can induce endothelial cells to synthesize and release tissue factor.

Platelets adhere to the exposed sub-endothelial collagen where the endothelium has been lost.

Platelets adhere via von Willebrand's factor (vWF) and tissue factor is released by adjacent damaged tissue activating the coagulation cascade.

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Loss or injury to endothelium results in decreased PGI2 and nitric oxide which normally inhibits platelet aggregation and causes vasodilation.

Thromboxane A2 (TXA2) from platelets causes vasoconstriction and in conjunction with ADP stimulates aggregation.

Here are some examples of thrombosis due to endothelial cell damage:
We are looking at the aortic valves of an older dog. Note the cauliflower-like vegetative growths on the valves. How did these THROMBI form?
This dog was uremic. The wall of the atrium has deposits of mineral on it. Pathogenesis? and could this lead to thrombosis?
Trauma from repeated venipuncture, catheters, or repeated injections with caustic medications results in endothelial damage and thrombosis. This horse died. Wanna see why?

Jugular thrombosis is often associated with repeated injections or with indwelling catheters.

From a horse with recurring colic - this is the aorta running across the top of the photograph and the cranial mesenteric artery projecting below. Holy mackerel - the cranial mesenteric artery is all plugged with a big old thrombus. How the heck did this happen and what might be the result?
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