Thrombosis

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Thrombosis

Cyanosis of the lower right extremity, resulting from acute arterial

thrombosis of the right leg (on the left side of the image)

Classification and external resources

ICD-10

I80-I82

ICD-9

437.6, 453, 671.5, 671.9

MeSH

D013927

Thrombosis (Greek: ) is the formation of a blood clot (thrombus; Greek: )

inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood
vessel is injured, the body uses platelets(thrombocytes) and fibrin to form a blood clot to prevent
blood loss. Even when a blood vessel is not injured, blood clots may form in the body under certain
conditions. A clot that breaks free and begins to travel around the body is known as an embolus.[1][2]
When a thrombus is significantly large enough to reduce the blood flow to a
tissue, hypoxia (oxygen deprivation) can occur and metabolic products such as lactic acid can
accumulate. A larger thrombus causing a much greater obstruction to the blood flow may result
in anoxia, the complete deprivation of oxygen and infarction, tissue death. There are also a number
of other conditions that can arise according to the location of the thrombus and the organs affected.
Thromboembolism is the combination of thrombosis and its main complication,embolism.
Contents
[hide]

1 Causes

1.1 Hypercoagulability

1.2 Endothelial cell injury

1.3 Disturbed blood flow

2 Classification
o

2.1 Venous thrombosis

2.2 Arterial thrombosis

3 Natural history

4 Embolization

5 Prevention

6 Treatment

7 See also

8 References

9 External links

Causes[edit]
In classical terms, thrombosis is caused by abnormalities in one or more of the following (Virchow's
triad):

The composition of the blood (hypercoagulability or thrombophilia)

Quality of the vessel wall (endothelial cell injury)

Nature of the blood flow (stasis, turbulence)

Hypercoagulability[edit]
Main article: Thrombophilia
Hypercoagulability is caused by, for example, genetic deficiencies or autoimmune disorders. Recent
studies indicate that neutrophils play a pivotal role in deep vein thrombosis, mediating numerous
pro-thrombotic actions.[3][4][5]

Endothelial cell injury[edit]

Causes of injury to the vessel's wall include trauma, surgery, infection or turbulent flow at
bifurcations. The main mechanism is exposure of tissue factor to the blood coagulation system.[6]

Disturbed blood flow[edit]

Further information: Blood flow

Causes of disturbed blood flow include stagnation of blood flow past the point of injury, or venous
stasis which may occur inheart failure,[6] in or after long periods of sedentary behavior, such as sitting
on a long airplane flight. Also, atrial fibrillation, causes stagnant blood in the left atrium (LA) or left
atrial appendage (LAA), and can lead to a thromboembolism.[6] Cancersor malignancies such as
leukemia may cause increased risk of thrombosis by possible activation of the coagulation system
by cancer cells or secretion of procoagulant substances (paraneoplastic syndrome), by external
compression on a blood vessel when a solid tumor is present, or (more rarely) extension into the
vasculature (for example, renal cell cancers extending into the renal veins). [6] Also, treatments for
cancer (radiation, chemotherapy) often cause additional hypercoagulability.[6]

Classification[edit]
There are two distinct forms of thrombosis, venous thrombosis and arterial thrombosis, each of
which can be presented by several subtypes.

Venous thrombosis[edit]
Main article: Venous thrombosis
Venous thrombosis is the formation of a thrombus (blood clot) within a vein. There are several
diseases which can be classified under this category:
Deep vein thrombosis[edit]
Main article: Deep vein thrombosis
Deep vein thrombosis (DVT) is the formation of a blood clot within a deep vein. It most commonly
affects leg veins, such as the femoral vein. Three factors are important in the formation of a blood
clot within a deep veinthese are the rate of blood flow, the thickness of the blood and qualities of
the vessel wall. Classical signs of DVT include swelling, pain and redness of the affected area.
Portal vein thrombosis[edit]
Main article: Portal vein thrombosis
Portal vein thrombosis affects the hepatic portal vein, which can lead to portal hypertension and
reduction of the blood supply to the liver.[7] It usually has a pathological cause such
as pancreatitis, cirrhosis, diverticulitis or cholangiocarcinoma.
Renal vein thrombosis[edit]
Main article: Renal vein thrombosis
Renal vein thrombosis is the obstruction of the renal vein by a thrombus. This tends to lead to
reduced drainage from the kidney. Anticoagulation therapy is the treatment of choice.
Jugular vein thrombosis[edit]
Main article: Jugular vein thrombosis
Jugular vein thrombosis is a condition that may occur due to infection, intravenous drug use or
malignancy. Jugular vein thrombosis can have a varying list of complications, including: systemic
sepsis, pulmonary embolism, and papilledema. Though characterized by a sharp pain at the site of
the vein, it can prove difficult to diagnose, because it can occur at random. [8]
Budd-Chiari syndrome[edit]
Main article: Budd-Chiari syndrome
Budd-Chiari syndrome is the blockage of the hepatic vein or the inferior vena cava. This form of
thrombosis presents withabdominal pain, ascites and hepatomegaly. Treatment varies between
therapy and surgical intervention by the use ofshunts.
Paget-Schroetter disease[edit]
Main article: Paget-Schroetter disease

Paget-Schroetter disease is the obstruction of an upper extremity vein (such as the axillary
vein or subclavian vein) by a thrombus. The condition usually comes to light after vigorous exercise
and usually presents in younger, otherwise healthy people. Men are affected more than women.
Cerebral venous sinus thrombosis[edit]
Main article: Cerebral venous sinus thrombosis
Cerebral venous sinus thrombosis (CVST) is a rare form of stroke which results from the blockage of
the dural venous sinuses by a thrombus. Symptoms may include headache, abnormal vision, any of
the symptoms of stroke such as weakness of the face and limbs on one side of the body
and seizures. The diagnosis is usually made with a CT or MRI scan. The majority of persons
affected make a full recovery. The mortality rate is 4.3%.[9]
Cavernous sinus thrombosis[edit]
Main article: Cavernous sinus thrombosis
Cavernous sinus thrombosis is a specialised form of cerebral venous sinus thrombosis, where there
is thrombosis of thecavernous sinus of the basal skull dura, due to the retrograde spread of infection
and endothelial damage from the danger triangle of the face. The facial veins in this area
anastomose with the superior and inferior ophthalmic veins of the orbit, which drain directly
posteriorly into the cavernous sinus through the superior orbital
fissure. Staphyloccoal or Streptococcalinfections of the face, for example nasal or upper lip pustules
may thus spread directly into the cavernous sinus, causing stroke-like symptoms of double
vision, squint, as well as spread of infection to cause meningitis.[citation needed]

Arterial thrombosis[edit]
Arterial thrombosis is the formation of a thrombus within an artery. In most cases, arterial thrombosis
follows rupture ofatheroma, and is therefore referred to as atherothrombosis.
Another common cause of arterial occlusion is atrial fibrillation, which causes a blood stasis within
the atria with easy thrombus formation. In addition, it is well known that the direct
current cardioversion of atrial fibrillation carries a great risk of thromboembolism, especially if
persisting more than 48 hours. Thromboembolism strikes approximately 5% of cases not
receiving anticoagulant therapy. When cardiac rhythm is restored clots are pushed out from atria to
ventricles and from these to the aorta and its branches.[10]
Arterial thrombosis can embolize and is a major cause of arterial embolism, potentially
causing infarction of almost any organ in the body.
Stroke[edit]
Main article: Stroke
A stroke is the rapid decline of brain function due to a disturbance in the supply of blood to the brain.
This can be due toischemia, thrombus, embolus (a lodged particle) or hemorrhage (a bleed). In
thrombotic stroke, a thrombus (blood clot) usually forms around atherosclerotic plaques. Since
blockage of the artery is gradual, onset of symptomatic thrombotic strokes is slower. Thrombotic
stroke can be divided into two categorieslarge vessel disease and small vessel disease. The
former affects vessels such as the internal carotids, vertebral and the circle of Willis. The latter can
affect smaller vessels such as the branches of the circle of Willis.
Myocardial infarction[edit]
Main article: Myocardial infarction
Myocardial infarction (MI) or heart attack, is caused by ischemia, (restriction in the blood supply),
often due to the obstruction of a coronary artery by a thrombus. This restriction gives an insufficient
supply of oxygen to the heart muscle which then results in tissue death,(infarction). A lesion is then
formed which is the infarct. MI can quickly become fatal if emergency medical treatment is not

received promptly. If diagnosed within 12 hours of the initial episode (attack) thenthrombolytic
therapy is initiated.
Other sites[edit]
Hepatic artery thrombosis usually occurs as a devastating complication after liver transplantation.[11]
An arterial embolus can also form in the limbs.[12]

Natural history[edit]
If a thrombus forms inside a blood vessel, without medical intervention the thrombosis may proceed
to several possible outcomes:[citation needed]
1. Embolisation: the thrombus detaches from the underlying endothelial wall, leading to
distal embolisation and vessel occlusion. An arterial thromboembolus may lead to
a stroke, central retinal artery occlusion, ischaemic limb,mesenteric ischaemia or some form
of localised ischaemia depending on the arterial circulation of the embolus. A venous
thromboembolus may occlude the pulmonary artery leading to pulmonary embolism.
2. Lysis: the thrombus may be acutely lysed by circulatory plasmin. This is essentially the
physiological equivalent to pharmacological thrombolysis performed in the hospital.
3. Ischaemia/infarction: if an arterial thrombus cannot be lysed by the body and it does not
embolise, and if the thrombus is large enough to impair or occlude blood flow in the involved
artery, then local ischaemia or infarction will result. A venous thrombus may or may not be
ischaemic, since veins distribute deoxygenated blood that is less vital for cellular
metabolism. Nevertheless, non-ischaemic venous thrombosis may still be problematic, due
to the swelling caused by blockage to venous drainage. In deep vein thrombosis this
manifests as pain, redness, and swelling; inretinal vein occlusion this may result in macular
oedema and visual acuity impairment, which if severe enough can lead to blindness.
4. Organisation: following the thrombotic event, residual vascular thrombus will be re-organised
histologically with several possible outcomes. For a occlusive thrombus (defined as
thrombosis within a small vessel that leads to complete occlusion), wound healing will
reorganise the occlusive thrombus into collagenous scar tissue, where the scar tissue will
either permanently obstruct the vessel, or contract down with myofibroblastic activity to
recanalise thelumen. For a mural thrombus (defined as a thrombus in a large vessel that
restricts the blood flow but does not occlude completely), histological reorganisation of the
thrombus does not occur via the classic wound healingmechanism. Instead, the plateletderived growth factor degranulated by the clotted platelets will attract a layer ofsmooth
muscle cells to cover the clot, and this layer of mural smooth muscle will be vascularised by
the blood inside the vessel lumen rather than by the vasa vasorum.

Embolization[edit]
Further information: Embolus
If a bacterial infection is present at the site of thrombosis, the thrombus may break down, spreading
particles of infected material throughout the circulatory system (pyemia, septic embolus) and setting
up metastatic abscesses wherever they come to rest. Without an infection, the thrombus may
become detached and enter circulation as an embolus, finally lodging in and completely obstructing
a blood vessel, which unless treated very quickly will lead to tissue necrosis (an infarction) in the
area past the occlusion. If the occlusion is in the coronary artery, myocardial ischaemia is likely to

occur, wherebycardiac myocytes cannot function properly due to lack of oxygen. This lack of oxygen
is then likely to result in a myocardial infarction.
Most thrombi, however, become organized into fibrous tissue, and the thrombosed vessel is
gradually recanalized.

Prevention[edit]
Prophylaxis of venous thromboembolism with heparin in medical patients does not appear to
decrease mortality and while it may decrease the risk of pulmonary embolism and deep vein
thrombosis it increases the risk of bleeding and thus results in little or no overall clinical benefit. [13]
[14]
Mechanical measures also appeared of little benefit in this group and in those with
astroke resulted in harm.[13] Evidence supports the use of heparin following surgery which has a high
risk of thrombosis to reduce the risk of DVTs; however the effect on PEs or overall mortality is not
known.[15][16][17]
Generally, a risk-benefit analysis is required, as all anticoagulants lead to a small increase in the risk
of major bleeding. Inatrial fibrillation, for instance, the risk of stroke (calculated on the basis of
additional risk factors, such as advanced age andhigh blood pressure) needs to outweigh the small
but known risk of major bleeding associated with the use of warfarin.[18]
In people admitted to hospital, thrombosis is a major cause for complications and occasionally
death. In the UK, for instance, the Parliamentary Health Select Committee heard in 2005 that the
annual rate of death due to thrombosis was 25,000, with at least 50% of these being hospitalacquired.[19] Hence thromboprophylaxis (prevention of thrombosis) is increasingly emphasized. In
patients admitted for surgery, graded compression stockings are widely used, and in severe illness,
prolonged immobility and in all orthopedic surgery, professional guidelines recommend low
molecular weight heparin (LMWH) administration, mechanical calf compression or (if all else is
contraindicated and the patient has recently suffered deep vein thrombosis) the insertion of a vena
cava filter.[20][21] In patients with medical rather than surgical illness, LMWH too is known to prevent
thrombosis,[21][22] and in the United Kingdom the Chief Medical Officer has issued guidance to the
effect that preventative measures should be used in medical patients, in anticipation of formal
guidelines.[19]
However, thromboprophylaxis can lead to complications such as bleeding. There are new, noninvasive ways to stratify bleeding risk for patients with VTE and PE, by using tools like the RIETE
Registry. The RIETE registry is an interactive database which uses data from previous and current
patients, even groups not typically recruited like women and elderly as well as those with preexisting conditions like Cancer or renal failure. The RIETE Registry offers more personalized options
for patients with clotting risk, and it also has created a predictive calculator based on the registry's
findings.[23]

Treatment[edit]
Coumadins, Vitamin K antagonists, are anticoagulants that can be taken orally to reduce
thromboembolic occurrence. Where a more effective response is required, heparin can be given (by
injection) concomitantly. As a side effect of any anticoagulant, the risk of bleeding is increased, so
the international normalized ratio of blood is monitored. Self-monitoring and self-management are
safe options for competent patients, though their practice varies. In Germany, about 20% of patients
were self-managed while only 1% of U.S. patients did home self-testing (according to one 2012
study).[24]

See also[edit]

National Blood Clot Alliance

Blood clotting tests

References[edit]
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