A thrombus, or colloquially a blood clot, is the final product of the blood coagulation
step in hemostasis.
Note, a thrombus is a solid or semi-solid mass formed from the constituents of blood
within the vascular system during life, whereas a blood clot refers to one that is formed
post-mortem.
There are two components to a thrombus, aggregated platelets that form a platelet plug, and a
mesh of cross-linked fibrin protein.
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 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 which represent bands of fibrin
with entrapped white blood cells and red blood cells.
Pathophysiology 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.
In a small blood vessel, blood flow may be completely cut-off 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 elevate risk of blood clots developing include atrial fibrillation,
heart valve replacement, a recent heart attack, extended periods of inactivity, 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.
This process is regulated through thromboregulation.
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.
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.
This drug is made by transgenic bacteria and it converts plasminogen into the clot-dissolving
enzyme plasmin.
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.
As of 2012, this enzyme has now been successfully produced by genetically engineered bacteria
and administered to cardiac patients.
Ultrasound-accelerated thrombolysis A recent multicenter randomized trial compared
standard catheter-directed thrombolysis versus ultrasound-accelerated thrombolysis for the
treatment of acute peripheral arterial thrombotic occlusions.
Results showed that, on average, patients treated with USAT were completed 12 hours
sooner than those treated with standard CDT with no increase in "serious adverse events."
Plans are underway to commence the DUET II study, which will be a non-randomized trial
using the EKOS system with an even lower hourly drug dose with an expectation of further reducing
bleeding complications.
Recent studies Recent research shows that chemicals found
in certain foods as onions, apples and oranges could help prevent blood clots.
Researchers claim that rutin found in black and green teas also could help prevent the
formation of clots and therefore could help in future treatments to protect against strokes
and heart attacks.
Presentation Virchow's triad describes the pathogenesis
of thrombus formation: Endothelial injury
Abnormal blood flow Hypercoagulability)
Disseminated intravascular coagulation 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.
Thoracic aortic thrombus is a rare pathology that usually originates from an atherosclerotic
aortic wall lesion or an aortic aneurysm and is a potential source of visceral, cerebral
and peripheral embolism.
Prognosis Thrombus formation can have one of four outcomes:
propagation, embolization, dissolution, and organization and recanalization.
Propagation of a thrombus occurs towards the direction of the heart.
This means that it is anterograde in veins or retrograde in arteries.
Embolization occurs when the thrombus breaks free from the vascular wall and becomes mobile.
A venous emboli 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.
Dissolution occurs when fibrinolytic mechanisms break up the thrombus and blood flow is restored
to the vessel.
This may be aided by drugs.
The best response to fibrinolytic drugs is within a couple of hours, before the fibrin
meshwork of the thrombus has been fully developed.
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.
Additional images
See also Embolism
Thrombolysis Thrombogenicity
National Blood Clot Alliance Prothrombin time
References
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.