Thrombus

From Wikipedia, the free encyclopedia
  (Redirected from Cerebral thrombosis)
Jump to navigation Jump to search
Thrombus
SynonymsBlood clot
Blood clot diagram.png
Diagram of a thrombus (blood clot) that has blocked a blood vessel valve
SpecialtyVascular surgery

A thrombus, colloquially called a blood clot, is the final product of the blood coagulation step in hemostasis. There are two components to a thrombus: aggregated platelets and red blood cells that form a plug, and a mesh of cross-linked fibrin protein. The substance making up a thrombus is sometimes called cruor. A thrombus is a healthy response to injury intended to prevent bleeding, but can be harmful in thrombosis, when clots obstruct blood flow through healthy blood vessels.

Mural thrombi are thrombi that adhere to the wall of a blood vessel. They occur in large vessels such as the heart and aorta, and can restrict blood flow but usually do not block it entirely. They appear grey-red with alternating light and dark lines (known as lines of Zahn) which represent bands of fibrin (lighter) with entrapped white blood cells and red blood cells (darker).

Cause[edit]

Virchow's triad describes the pathogenesis of thrombus formation:[1][2]

  1. Endothelial injury: Injury to the endothelial causing platelet activation and aggregation
  2. Stasis: Blood stasis promotes greater contact between platelets/coagulative factors with vascular endothelium.
    • Common causes of stasis include anything that leads to prolonged immobility and reduced blood flow such as: trauma/broken bones and extended air travel
  3. Hypercoagulability (also called thrombophilia; any disorder of the blood that predisposes to thrombosis)
    • Common causes include: cancer (leukaemia), Factor V mutation (Leiden) - prevents Factor V inactivation leading to increased coagulability.

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, as well as platelets and heparin to prevent further thrombi formation.

Classification[edit]

Thrombi are classified in three major groups depending on the relative amount of platelets and red blood cells (RBCs).[3] The three major groups are:

  1. White thrombi (characterized by predominance of platelets)
  2. Red thrombi (characterized by predominance of red blood cells)
  3. Mixed thrombi (with features of both white and red thrombi - an intermediate).

Pathophysiology[edit]

Animation of the formation of an occlusive thrombus in a vein. A few platelets attach themselves to the valve lips, constricting the opening and causing more platelets and red blood cells to aggregate and coagulate. Coagulation of unmoving blood on both sides of the blockage may propagate a clot in both directions.

A thrombus occurs when the hemostatic process, which normally occurs in response to injury, becomes activated 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 considered an embolus.

Some of the conditions which increase the 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[edit]

Platelet activation can occur through different mechanisms such as a vessel wall breach that exposes collagen, or tissue factor encryption.[clarification needed] The platelet activation causes a cascade of further platelet activation, eventually causing the formation of the thrombus.[4] This process is regulated through thromboregulation.

Prevention and treatment[edit]

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; with the former used for acute anticoagulation while the latter is used for long term anti-coagulability.[2] The mechanism of action of Heparin and Warfarin are vastly different as they work on different pathways of the coagulation cascade. Heparin works by binding to and activating the enzyme inhibitor Antithrombin III, an enzyme that acts by inactivating thrombin and Xa. In contrast, Warfarin works by inhibiting vitamin K epoxide reductase, an enzyme needed to synthesize vitamin K dependent clotting factors II XII IX and X.[5] Bleeding time with heparin and warfarin therapy can be measured with the partial thromboplastin time (PTT) and prothrombin time (PT) respectively.[5]

Some treatments have been derived from bacteria. One drug is streptokinase, which is an enzyme secreted by several streptococcal bacteria. This drug is administered intravenously and can be used to dissolve blood clots in coronary vessels. However, streptokinase is nonspecific and can digest almost any protein, which can lead to many secondary problems. Another clot-dissolving enzyme that works faster and is more specific is called tissue plasminogen activator (tPA). This drug is made by transgenic bacteria and it converts plasminogen into the clot-dissolving enzyme plasmin.[6] There are also some anticoagulants that come from animals that work by dissolving fibrin. For example, Haementeria ghilianii, an Amazon leech, produces an enzyme called hementin from its salivary glands.[7] As of 2012, this enzyme has now been successfully produced by genetically engineered bacteria and administered to cardiac patients.

More recent research indicates that tPA could have toxic effects in the central nervous system. In cases of severe stroke, tPA can cross the blood-brain barrier and enter interstitial fluid, where it then increases excitotoxicity, further damages the blood-brain barrier, and may even cause cerebral hemorrhaging.[8]

Prognosis[edit]

Thrombus formation can have one of four outcomes: propagation, embolization, dissolution, and organization and recanalization.[9]

  1. Propagation of a thrombus occurs towards the direction of the heart and involves the accumulation of additional platelets and fibrin. 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, thereby traveling to other sites in the vasculature. A venous embolus (mostly from deep vein thrombosis in the lower limbs) will travel through the systemic circulation, reach the right side of the heart, and travel through the pulmonary artery resulting in a pulmonary embolism. 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 the fibrinolytic mechanisms break up the thrombus and blood flow is restored to the vessel. This may be aided by fibrinolytic drugs such as Tissue Plasminogen Activator (tPA) in instances of coronary artery occlusion. 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.[1]

See also[edit]

References[edit]

  1. ^ a b Robbins and Cotran pathologic basis of disease. Kumar, Vinay, 1944-, Abbas, Abul K.,, Aster, Jon C.,, Perkins, James A., (Ninth ed.). Philadelphia, PA. ISBN 9781455726134. OCLC 879416939.
  2. ^ a b "Venous thromboembolism (VTE) | McMaster Pathophysiology Review". www.pathophys.org. Retrieved 2018-11-03.
  3. ^ "White Thrombi". Bayer. Retrieved 27 October 2015.
  4. ^ Furie, Bruce; Furie, Barbara (2008). "Mechanisms of Thrombus Formation". The New England Journal of Medicine. 359 (9): 938–49. doi:10.1056/NEJMra0801082. PMID 18753650.
  5. ^ a b Pharmacology. Whalen, Karen,, Finkel, Richard (Richard S.),, Panavelil, Thomas A., (Sixth ed.). Philadelphia. ISBN 9781451191776. OCLC 881019575.
  6. ^ Saladin, Kenneth S. (2012). Anatomy & Physiology: The Unity of Form and Function (6th ed.). New York, NY: McGraw-Hill. p. 710. ISBN 978-0-07-337825-1.
  7. ^ Malinconico, S. M., J. B. Katz, and A. Z. Budzynski. "Hementin: Anticoagulant Protease from the Salivary Gland of the Leech Haementeria Ghilianii." National Center for Biotechnology Information. U.S. National Library of Medicine, n.d. Web. 11 Dec. 2012.
  8. ^ Medcalf, R. "Plasminogen activation-based thrombolysis for ischaemic stroke: the diversity of targets may demand new approaches". Current Drug Targets. 12: 1772–1781. doi:10.2174/138945011797635885.
  9. ^ Kumar, Vinay; et al. (2007). Robbins Basic Pathology (8th ed.). Philadelphia: Saunders/Elsevier. ISBN 978-1-4160-2973-1.

External links[edit]

Classification