Thrombus

A thrombus (Greek θρόμβος), or blood clot, is the final product of the blood coagulation step in hemostasis. It is achieved via the aggregation of platelets that form a platelet plug, and the activation of the humoral coagulation system (i.e. clotting factors). A thrombus is normal in cases of injury, but pathologic in instances of thrombosis.

Mural thrombi are thrombi adherent to the vessel wall. They are not occlusive and affect large vessels, such as heart and aorta. Grossly they appear grey-red with alternating light and dark lines (lines of Zahn) which represent bands of fibrin (darker) with entrapped white blood cells and red blood cells (lighter).

Pathophysiology

Specifically, a thrombus is the inappropriate activation of the hemostatic process in an uninjured or slightly injured vessel. A thrombus in a large blood vessel will decrease blood flow through that vessel (termed a mural thrombus). In a small blood vessel, blood flow may be completely cut-off (termed an occlusive thrombus) resulting in death of tissue supplied by that vessel. If a thrombus dislodges and becomes free-floating, it is termed as an embolus.

Some of the conditions which elevate risk of blood clots developing include atrial fibrillation (a form of cardiac arrhythmia), heart valve replacement, a recent heart attack (also known as a myocardial infarction), extended periods of inactivity (see deep venous thrombosis), and genetic or disease-related deficiencies in the blood's clotting abilities.

Formation

Platelet activation can occur through different mechanisms such as a vessel wall breach that exposes collagen, or tissue factor encryption. The platelet activation causes a cascade of further platelet activation eventually causing the formation of the thrombus.^[1]

Treatment

Blood clot prevention and treatment reduces the risk of stroke, heart attack and pulmonary embolism. Heparin and warfarin are often used to inhibit the formation and growth of existing thrombi; the former binds to and activates the enzyme inhibitor antithrombin III, while the latter inhibits vitamin K epoxide reductase, an enzyme needed to synthesize mature clotting factors.

Presentation

Virchow's triad describes the pathogenesis of thrombus formation:

1. Endothelial injury (injury to the endothelial cells that line enclosed spaces of the body, such as the inside of blood vessels) (e.g. trauma, atheroma)
2. Abnormal blood flow (loss of laminar flow resulting from stasis in veins or turbulence in arteries) (e.g. valvulitis, aneurysm)
3. Hypercoagulability (e.g. leukaemia, Factor V mutation (Leiden))

Disseminated intravascular coagulation (DIC) involves widespread microthrombi formation throughout the majority of the blood vessels. This is due to excessive consumption of coagulation factors and subsequent activation of fibrinolysis using all of the body's available platelets and clotting factors. The end result is hemorrhaging and ischaemic necrosis of tissue/organs. Causes are septicaemia, acute leukaemia, shock, snake bites, fat emboli from broken bones, or other severe traumas. DIC may also be seen in pregnant females. Treatment involves the use of fresh frozen plasma to restore the level of clotting factors in the blood, platelets and heparin to prevent further thrombi formation.

Prognosis

Thrombus formation can have one of five outcomes: propagation, embolization, dissolution, organization and organization with recanalization.^[2]

1. Propagation of a thrombus occurs towards the direction of the heart. This means that it is anterograde in veins or retrograde in arteries.
2. Embolization occurs when the thrombus breaks free from the vascular wall and becomes mobile. A venous emboli (most likely from deep venous thrombosis in the lower extremities) will travel through the systemic circulation, reach the right side of the heart, and travel through the pulmonary artery resulting in a pulmonary embolism. On the other hand, arterial thrombosis resulting from hypertension or atherosclerosis can become mobile and the resulting emboli can occlude any artery or arteriole downstream of the thrombus formation. This means that cerebral stroke, myocardial infarction, or any other organ can be affected.
3. Dissolution occurs when fibrinolytic mechanisms break up the thrombus and blood flow is restored to the vessel. This may be aided by drugs (for example after occlusion of a coronary artery). The best response to fibrinolytic drugs is within a couple of hours, before the fibrin meshwork of the thrombus has been fully developed.
4. Organization and recanalization involves the ingrowth of smooth muscle cells, fibroblasts and endothelium into the fibrin-rich thrombus. If recanalization proceeds it provides capillary-sized channels through the thrombus for continuity of blood flow through the entire thrombus but may not restore sufficient blood flow for the metabolic needs of the downstream tissue.

See also

• Embolism
• Thrombolysis ("Destruction of clot")
• Thrombogenicity (the tendency to clot)
• National Blood Clot Alliance
• http://www.attract.wustl.edu Blood Clot in Leg - Study

References

1. ^ Furie, Bruce; Furie, Barbara (2008). "Mechanisms of Thrombus Formation". The New England Journal of Medicine 359 (9). doi:10.1056/NEJMra0801082. PMID 18753650. http://www.nejm.org/doi/full/10.1056/NEJMra0801082. 
2. ^ Robbins Basic Pathology; ISBN 978-1-4160-2973-1

External links

• Treatment and Symptoms of Blood Clots -- MDhealthnetwork.org, Medical Information Resource, 1999
• North American Thrombosis Forum - NATF is a nonprofit organization dedicated to promoting thrombosis research, prevention and education, public policy, and advocacy outreach.
• Muscle Relaxing Drugs Can Reduce Lethal Blood Clots
• Air Pollution Triggers Blood Clots - US Study.
• The National Alliance for Thrombosis and Thrombophilia - has extensive stories from patients and family members on living with Thrombosis and Thrombophilia, assembled frequently asked questions and created publications addressing specific blood clot issues.