Thrombosis

General pathology
Thrombosis:
Introduction:
Normal blood flow is the result of a set of well-regulated processes that accomplish two important functions:
(1) They maintain blood in a fluid, clot-free state in normal vessels.
(2) they are able to induce a rapid and localized plug at a site of vascular injury.
The normal blood flow depend on the following:
• Endothelial cells.
• Platelets.
• Coagulating system.
• Fibrinolytic system.
Physiology of clot formation:
After initial injury, there is a brief period of arteriolar vasoconstriction, due to reflex neurogenic mechanisms that stimulated by the local secretion of factors called endothelin. Endothelial injury exposes highly thrombogenic subendothelial element, which allows platelets to adhere and become activated, that is, undergo a shape change and release secretory granules. Within minutes, the secreted products have recruited additional platelets to form a plug; this is the process of primary hemostasis, Tissue factor, a membrane-bound procoagulant factor synthesized by endothelium, is also exposed at the site of injury. It acts in conjunction with the secreted platelet factors to activate the coagulation cascade, culminating in the activation of thrombin. In turn, thrombin converts circulating soluble fibrinogen to insoluble fibrin resulting in local fibrin deposition. Thrombin also induces further platelet recruitment and granules release. This sequence, secondary hemostasis, takes longer than the initial platelet plug Polymerized fibrin and platelet aggregates form a solid, permanent plug to prevent any further hemorrhage. At this stage, counter regulatory mechanisms (e.g., tissue plasminogen activator [t-PA]) are set into motion to restrict the hemostatic plug to the site of injury .
Thrombosis
It is defined as formation of solid or semisolid mass from the constitute of blood within the vascular system during life.
The formed mass it self called (thrombus).
Pathogenesis.
Three primary influences predispose to thrombus formation, they so-called Virchow s triad:
(1) endothelial injury.
(2) stasis and change of blood flow.
(3) blood hypercoagulability .

Endothelial Injury.
Endothelial injury is particularly important in thrombus formation in the heart and arterial circulation, for example:
1-Within the cardiac chambers when there has been endocardial injury (e.g., myocardial infarction or valvulitis).
2- Over ulcerated plaques in severely atherosclerotic arteries.
3-At sites of inflammatory vascular injury (vasculitis).
4-Hemodynamic stress associated with hypertension.
What ever the cause of endothelial injury, the end results include exposure of subendothelial collagen (and other platelet activators), adherence of platelets, exposure of tissue factor, and thrombus formation.

Alteration in normal blood flow and stasis:
stasis; stasis is a major factor in the development of venous thrombi. Normal blood flow is central laminar, that is, the cellular elements flow centrally in the vessel lumen, separated from the endothelium by a slower moving clear zone of plasma.
Stasis and turbulence therefore lead to following:
1-Disrupt laminar flow and bring platelets into contact with the endothelium.
2-Prevent dilution of activated clotting factors by fresh flowing blood.

Abnormal aortic and arterial dilations called aneurysms cause local stasis and are favored sites of thrombosis, also the Myocardial infarctions not only have associated endothelial injury, but also have regions of non-contractile myocardium, adding an element of stasis in the formation of mural thrombi. Mitral valve stenosis (e.g., after rheumatic heart disease) results in left atrial dilation a dilated atrium is a site of profound stasis and a prime location for thrombus development.
Hypercoagulability.
It is defined as any alteration of the coagulation pathways that predisposes to thrombosis and can be divided into:
• primary (genetic) : {deficiency of Antithrombin III, or protein S+C}
• secondary (acquired): { Cancer, surgical operation, prosthetic valve, and prolonged immobilization}.
Morphology and composition of thrombus:
This depends on the speed of blood flow where the thrombus formed:

((Venous thrombosis))
There are of two types:
1- thrombophlebitis:
a- Septic thrombophlebitis seen within veins draining septic foci and
at site of cellulites.
b- Aseptic thrombophlebitis, at site of mechanical injury and irradiation.
2- Phlebothrombosis:
a- patients with chronic heart failure, and deep venous thrombosis.
b- thrombosis seen in patient after operation, and bed ridden patients.
((Arterial thrombosis))
1- At sites of atherosclerosis.
2- Arterial aneurismal sites.
3- Conditions associated with endothelial inflammation.
Appearance and composition:
it depends on speed of blood flow:
1- pale thrombus:
seen at arterial site with rapid blood flow, it composed of platelets and fibrin with few RBCs, so it is firm and pale.
2- red thrombus:
seen at venous site mainly where blood is stagnant, its soft, red and composed from network of fibrin with a lot of RBCs, and leucocytes.
3 – mixed thrombus:
Seen in slowly flowing blood, also at veins, show alteration of dark and pale layers calls lines of Zahn, give the thrombus a laminated appearance.
At autopsy, postmortem clots may be confused for venous thrombi. Postmortem clots are gelatinous with a dark red dependent portion where red cells have settled by gravity and a yellow chicken fat supernatant; they are usually not attached to the underlying wall.
Fate of thrombus:
1- Propagation: The thrombus may accumulate more platelets and fibrin (propagate), eventually leading to vessel obstruction.
2 - Embolization: Thrombi may dislodge and travel to other sites in the vasculature.
3- Dissolution: Thrombi may be removed by fibrinolytic activity.
4-Organization and recanalization: Thrombi may induce inflammation and fibrosis (organization) and may eventually become recanalized, that is, may reestablish vascular flow, or may be incorporated into a thickened vascular wall.
EMBOLISM
An embolus is a detached intravascular solid, liquid, or gaseous mass that is carried by the blood to a site distant from its point of origin.
Virtually 99% of all emboli represent some part of a dislodged thrombus, hence Rare forms of emboli include droplets of fat, bubbles of air or nitrogen, atherosclerotic debris (cholesterol emboli), tumor fragments, bits of bone marrow, or foreign bodies.
The potential consequence of such thromboembolic events is the ischemic necrosis of distal tissue, known as infarction. Depending on the site of origin, emboli may lodge anywhere in the vascular tree; the clinical outcomes are best understood from the standpoint of whether emboli lodge in the pulmonary or systemic circulations.
Pulmonary embolism:
pulmonary embolism causes about 200,000 deaths per year in the United States. In more than 95% of instances, venous emboli originate from deep leg vein thrombi. They are carried through progressively larger channels and usually pass through the right side of the heart into the pulmonary vasculature.
Systemic thromboembolism:
It represent emboli traveling within the arterial circulation. Most (80%) arise from intracardiac mural thrombi, and from aortic aneurysms, thrombi on ulcerated atherosclerotic plaques, or fragmentation of a valvular vegetation arterial emboli can travel to a wide variety of sites; The major sites for arteriolar embolization are the lower extremities (75%) and the brain (10%), with the intestines, kidneys, spleen, and upper extremities involved to a lesser extent. The consequences of systemic emboli depend on any collateral vascular supply in the affected tissue, the tissue s vulnerability to ischemia, and the caliber of the vessel occluded.
Fat Embolism
Microscopic fat globules may be found in the circulation after fractures of long bones (which have fatty marrows or, rarely, in the setting of soft tissue trauma and burns). The fat is released by marrow or adipose tissue injury and enters the circulation by rupture of the marrow vascular sinusoids or of venules. Although traumatic fat embolism occurs in some 90% of individuals with severe skeletal injuries , less than 10% of such patients have any clinical findings characterized by onset of tachypnea, dyspnea, and tachycardia.
Air Embolism
Gas bubbles within the circulation can obstruct vascular flow and cause distal ischemic injury. Air may enter the circulation during obstetric procedures or as a consequence of chest wall injury. Generally, in excess of 100 cc is required to have a clinical effect.
Amniotic Fluid Embolism
Amniotic fluid embolism is a grave but uncommon (1 in 50,000 deliveries) complication of labor. The onset is characterized by sudden severe dyspnea, cyanosis, and hypotensive shock, followed by seizures and coma. The underlying cause is the infusion of amniotic fluid into the maternal circulation via a tear in the placental membranes and rupture of uterine veins. The classic findings are the presence in the pulmonary microcirculation of the mother an epithelial squamous cells shed from fetal skin, , and mucin derived from the fetal respiratory or gastrointestinal tract.