Thrombosis (from

Ancient Greek Ancient Greek includes the forms of the Greek language used in ancient Greece and the ancient world from around 1500 BC to 300 BC. It is often roughly divided into the following periods: Mycenaean Greek (), Dark Ages (), the Archaic peri ...

"clotting") is the formation of a

blood clot A thrombus (plural thrombi), 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 c ...

inside a

blood vessel The blood vessels are the components of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of the body. They also take waste and carbon dioxide away ...

, obstructing the flow of

blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the c ...

through the

circulatory system The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...

. When a blood vessel (a

vein Veins are blood vessels in humans and most other animals that carry blood towards the heart. Most veins carry deoxygenated blood from the tissues back to the heart; exceptions are the pulmonary and umbilical veins, both of which carry oxygenated b ...

or an

artery An artery (plural arteries) () is a blood vessel in humans and most animals that takes blood away from the heart to one or more parts of the body (tissues, lungs, brain etc.). Most arteries carry oxygenated blood; the two exceptions are the pul ...

) is injured, the body uses

platelets Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby ini ...

(thrombocytes) and

fibrin Fibrin (also called Factor Ia) is a fibrous, non-globular protein involved in the clotting of blood. It is formed by the action of the protease thrombin on fibrinogen, which causes it to polymerize. The polymerized fibrin, together with platele ...

to form a

to prevent blood loss. Even when a blood vessel is not injured, blood clots may form in the body under certain conditions. A clot, or a piece of the clot, that breaks free and begins to travel around the body is known as an

embolus An embolus (; plural emboli; from the Greek ἔμβολος "wedge", "plug") is an unattached mass that travels through the bloodstream and is capable of creating blockages. When an embolus occludes a blood vessel, it is called an embolism or emb ...

. Thrombosis may occur in veins (

venous thrombosis Venous thrombosis is blockage of a vein caused by a thrombus (blood clot). A common form of venous thrombosis is deep vein thrombosis (DVT), when a blood clot forms in the deep veins. If a thrombus breaks off (embolizes) and flows to the lungs to ...

) or in arteries (

arterial thrombosis Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thr ...

). Venous thrombosis (sometimes called DVT, deep vein thrombosis) leads to a blood clot in the affected part of the body, while arterial thrombosis (and, rarely, severe venous thrombosis) affects the blood supply and leads to damage of the tissue supplied by that artery (

ischemia Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems wi ...

and

necrosis Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated dige ...

). A piece of either an arterial or a venous thrombus can break off as an embolus, which could then travel through the circulation and lodge somewhere else as an

embolism An embolism is the lodging of an embolus, a blockage-causing piece of material, inside a blood vessel. The embolus may be a blood clot (thrombus), a fat globule ( fat embolism), a bubble of air or other gas (gas embolism), amniotic fluid (amniot ...

. This type of embolism is known as a ''thromboembolism''. Complications can arise when a

venous thromboembolism Venous thrombosis is blockage of a vein caused by a thrombus (blood clot). A common form of venous thrombosis is deep vein thrombosis (DVT), when a blood clot forms in the deep veins. If a thrombus breaks off (embolizes) and flows to the lungs to ...

(commonly called a VTE) lodges in the lung as a

pulmonary embolism Pulmonary embolism (PE) is a blockage of an pulmonary artery, artery in the lungs by a substance that has moved from elsewhere in the body through the bloodstream (embolism). Symptoms of a PE may include dyspnea, shortness of breath, chest pain p ...

. An arterial embolus may travel further down the affected blood vessel, where it can lodge as an embolism.

Signs and symptoms

Thrombosis is generally defined by the type of blood vessel affected (arterial or venous thrombosis) and the precise location of the blood vessel or the organ supplied by it.

Venous thrombosis

Deep vein thrombosis

Deep vein thrombosis (DVT) is the formation of a blood clot within a

deep vein A deep vein is a vein that is deep in the body. This contrasts with superficial veins that are close to the body's surface. Deep veins are almost always beside an artery with the same name (e.g. the femoral vein is beside the femoral artery). ...

. It most commonly affects leg veins, such as the

femoral vein In the human body, the femoral vein is a blood vessel that accompanies the femoral artery in the femoral sheath. It begins at the adductor hiatus (an opening in the adductor magnus muscle) as the continuation of the popliteal vein. It ends at th ...

. Three factors are important in the formation of a blood clot within a deep vein—these 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.

Paget-Schroetter disease

Paget-Schroetter disease or upper extremity DVT (UEDVT) is the obstruction of an

arm In human anatomy, the arm refers to the upper limb in common usage, although academically the term specifically means the upper arm between the glenohumeral joint (shoulder joint) and the elbow joint. The distal part of the upper limb between the ...

vein (such as the

axillary vein In human anatomy, the axillary vein is a large blood vessel that conveys blood from the lateral aspect of the thorax, axilla (armpit) and upper limb toward the heart. There is one axillary vein on each side of the body. Structure Its origin i ...

subclavian vein The subclavian vein is a paired large vein, one on either side of the body, that is responsible for draining blood from the upper extremities, allowing this blood to return to the heart. The left subclavian vein plays a key role in the absorption ...

) 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.

Budd-Chiari syndrome

Budd-Chiari syndrome is the blockage of a

hepatic vein In human anatomy, the hepatic veins are the veins that drain venous blood from the liver into the inferior vena cava (as opposed to the hepatic portal vein which conveys blood from the gastrointestinal organs to the liver). There are usually thr ...

or of the hepatic part of the

inferior vena cava The inferior vena cava is a large vein that carries the deoxygenated blood from the lower and middle body into the right atrium of the heart. It is formed by the joining of the right and the left common iliac veins, usually at the level of the ...

. This form of thrombosis presents with

abdominal pain Abdominal pain, also known as a stomach ache, is a symptom Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than ...

ascites Ascites is the abnormal build-up of fluid in the abdomen. Technically, it is more than 25 ml of fluid in the peritoneal cavity, although volumes greater than one liter may occur. Symptoms may include increased abdominal size, increased weight, ab ...

and

enlarged liver Hepatomegaly is the condition of having an enlarged liver. It is a non-specific medical sign having many causes, which can broadly be broken down into infection, hepatic tumours, or metabolic disorder. Often, hepatomegaly will present as an abdomi ...

. Treatment varies between therapy and surgical intervention by the use of shunts.

Portal vein thrombosis

Portal vein thrombosis affects the

hepatic portal vein The portal vein or hepatic portal vein (HPV) is a blood vessel that carries blood from the gastrointestinal tract, gallbladder, pancreas and spleen to the liver. This blood contains nutrients and toxins extracted from digested contents. Approxima ...

, which can lead to portal

hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

and reduction of the blood supply to the liver. It usually happens in the setting of another disease such as

pancreatitis Pancreatitis is a condition characterized by inflammation of the pancreas. The pancreas is a large organ behind the stomach that produces digestive enzymes and a number of hormones. There are two main types: acute pancreatitis, and chronic pancr ...

cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue repai ...

diverticulitis Diverticulitis, specifically colonic diverticulitis, is a gastrointestinal disease characterized by inflammation of abnormal pouches—diverticula—which can develop in the wall of the large intestine. Symptoms typically include lower abdominal ...

cholangiocarcinoma Cholangiocarcinoma, also known as bile duct cancer, is a type of cancer that forms in the bile ducts. Symptoms of cholangiocarcinoma may include abdominal pain, yellowish skin, weight loss, generalized itching, and fever. Light colored stool ...

Renal vein thrombosis

Renal vein thrombosis is the obstruction of the

renal vein The renal veins are large-calibre veins that drain blood filtered by the kidneys into the inferior vena cava. There is one renal vein draining each kidney. Because the inferior vena cava is on the right half of the body, the left renal vein is lo ...

by a thrombus. This tends to lead to reduced drainage from the kidney.

Cerebral venous sinus thrombosis

Cerebral venous sinus thrombosis (CVST) is a rare form of

stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...

which results from the blockage of the

dural venous sinuses The dural venous sinuses (also called dural sinuses, cerebral sinuses, or cranial sinuses) are venous channels found between the endosteal and meningeal layers of dura mater in the brain. They receive blood from the cerebral veins, receive cereb ...

by a thrombus. Symptoms may include

headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...

, abnormal vision, any of the symptoms of stroke such as weakness of the face and limbs on one side of the body and

seizures An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or neural oscillation, synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much o ...

. The diagnosis is usually made with a CT or

MRI scan Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio waves ...

. The majority of persons affected make a full recovery. The

mortality rate Mortality rate, or death rate, is a measure of the number of deaths (in general, or due to a specific cause) in a particular population, scaled to the size of that population, per unit of time. Mortality rate is typically expressed in units of de ...

is 4.3%.

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,

, and

papilledema Papilledema or papilloedema is optic disc swelling that is caused by increased intracranial pressure due to any cause. The swelling is usually bilateral and can occur over a period of hours to weeks. Unilateral presentation is extremely rare. In ...

. Though characterized by a sharp pain at the site of the vein, it can prove difficult to diagnose, because it can occur at random.

Cavernous sinus thrombosis

Cavernous sinus thrombosis The cavernous sinus within the human head is one of the dural venous sinuses creating a cavity called the lateral sellar compartment bordered by the temporal bone of the skull and the sphenoid bone, lateral to the sella turcica. Structure The cave ...

is a specialised form of cerebral venous sinus thrombosis, where there is thrombosis of the

cavernous sinus The cavernous sinus within the human head is one of the dural venous sinuses creating a cavity called the lateral sellar compartment bordered by the temporal bone of the skull and the sphenoid bone, lateral to the sella turcica. Structure The cave ...

of the basal skull dura, due to the retrograde spread of infection and endothelial damage from the

danger triangle The danger triangle of the face consists of the area from the corners of the mouth to the bridge of the nose, including the nose and maxilla. Due to the special nature of the blood supply to the human nose and surrounding area, it is possible ...

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 The superior orbital fissure is a foramen or cleft of the skull between the lesser and greater wings of the sphenoid bone. It gives passage to multiple structures, including the oculomotor nerve, trochlear nerve, ophthalmic nerve, abducens ner ...

. Staphyloccoal or

Streptococcal ''Streptococcus'' is a genus of gram-positive bacteria, gram-positive ' (plural ) or spherical bacteria that belongs to the family Streptococcaceae, within the order Lactobacillales (lactic acid bacteria), in the phylum Bacillota. Cell divisio ...

infections 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 Diplopia is the simultaneous perception of two images of a single object that may be displaced horizontally or vertically in relation to each other. Also called double vision, it is a loss of visual focus under regular conditions, and is often v ...

squint Squinting is the action of looking at something with partially closed eyes. Squinting is most often practiced by people who suffer from refractive errors of the eye who either do not have or are not using their glasses. Squinting helps momentari ...

, as well as spread of infection to cause

meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, headache, and neck stiffness. Other symptoms include confusion or ...

Arterial thrombosis

Arterial thrombosis is the formation of a thrombus within an

. In most cases, arterial thrombosis follows rupture of

atheroma An atheroma, or atheromatous plaque, is an abnormal and reversible accumulation of material in the inner layer of an arterial wall. The material consists of mostly macrophage cells, or debris, containing lipids, calcium and a variable amount o ...

(a fat-rich deposit in the blood vessel wall), and is therefore referred to as ''atherothrombosis''.

Arterial embolism Arterial embolism is a sudden interruption of blood flow to an organ or body part due to an embolus adhering to the wall of an artery blocking the flow of blood, the major type of embolus being a blood clot (thromboembolism). Sometimes, pulmona ...

occurs when clots then migrate downstream and can affect any organ.Alternatively, arterial occlusion occurs as a consequence of embolism of blood clots originating from the heart ("cardiogenic" emboli). The most common cause is atrial fibrillation, which causes a blood stasis within the atria with easy thrombus formation, but blood clots can develop inside the heart for other reasons too as infective endocarditis.

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 to

, thrombus,

(a lodged particle) or

hemorrhage Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, vag ...

(a bleed). In thrombotic stroke, a thrombus (blood clot) usually forms around

atherosclerotic Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheromatous plaque. At onset there are usually no sy ...

plaques. Since blockage of the artery is gradual, the onset of symptomatic thrombotic strokes is slower. Thrombotic stroke can be divided into two categories — large vessel disease or small vessel disease. The former affects vessels such as the

internal carotid The internal carotid artery (Latin: arteria carotis interna) is an artery in the neck which supplies the anterior circulation of the brain. In human anatomy, the internal and external carotids arise from the common carotid arteries, where these b ...

vertebral The vertebral column, also known as the backbone or spine, is part of the axial skeleton. The vertebral column is the defining characteristic of a vertebrate in which the notochord (a flexible rod of uniform composition) found in all chordates ...

and the

circle of Willis The circle of Willis (also called Willis' circle, loop of Willis, cerebral arterial circle, and Willis polygon) is a circulatory anastomosis that supplies blood to the brain and surrounding structures in reptiles, birds and mammals, including huma ...

. The latter can affect smaller vessels, such as the branches of the circle of Willis.

Myocardial infarction

Myocardial infarction (MI), or heart attack, is caused by ischemia (restriction in the blood supply), which is often due to the obstruction of a

coronary artery The coronary arteries are the arterial blood vessels of coronary circulation, which transport oxygenated blood to the heart muscle. The heart requires a continuous supply of oxygen to function and survive, much like any other tissue or organ of ...

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 Infarction is tissue death (necrosis) due to Ischemia, inadequate blood supply to the affected area. It may be caused by Thrombosis, artery blockages, rupture, mechanical compression, or vasoconstriction. The resulting lesion is referred to as a ...

. MI can quickly become fatal if emergency medical treatment is not received promptly. If diagnosed within 12 hours of the initial episode (attack) then

thrombolytic therapy Thrombolysis, also called fibrinolytic therapy, is the breakdown ( lysis) of blood clots formed in blood vessels, using medication. It is used in ST elevation myocardial infarction, stroke, and in cases of severe venous thromboembolism (massiv ...

is initiated.

Limb ischemia

An arterial thrombus or embolus can also form in the limbs, which can lead to

acute limb ischemia Acute limb ischaemia (ALI) occurs when there is a sudden lack of blood flow to a limb. Acute limb ischaemia is caused by embolism or thrombosis, or rarely by dissection or trauma. Thrombosis is usually caused by peripheral vascular disease (ath ...

Other sites

Hepatic artery thrombosis Hepatic artery thrombosis occurs when a blood clot forms in the artery that provides blood flow to the liver. Hepatic artery thrombosis may occur as a complication after liver transplantation, and represents the most common complication of liver t ...

usually occurs as a devastating complication after

liver transplantation Liver transplantation or hepatic transplantation is the replacement of a diseased liver with the healthy liver from another person (allograft). Liver transplantation is a treatment option for end-stage liver disease and acute liver failure, al ...

Causes

Thrombosis prevention is initiated with assessing the risk for its development. Some people have a higher risk of developing thrombosis and its possible development into thromboembolism. Some of these risk factors are related to

inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...

. "

Virchow's triad Virchow's triad or the triad of Virchow () describes the three broad categories of factors that are thought to contribute to thrombosis. *Hypercoagulability *Hemodynamic changes (stasis, turbulence) *Endothelial injury/dysfunction It is named a ...

" has been suggested to describe the three factors necessary for the formation of thrombosis: stasis of blood, vessel wall injury, and altered blood coagulation. Some risk factors predispose for venous thrombosis while others increase the risk of arterial thrombosis. Newborn babies in the neonatal period are also at risk of a thromboembolism.

Mechanism

Pathogenesis

The main causes of thrombosis are given in

which lists

thrombophilia Thrombophilia (sometimes called hypercoagulability or a prothrombotic state) is an abnormality of blood coagulation that increases the risk of thrombosis (blood clots in blood vessels). Such abnormalities can be identified in 50% of people who ...

endothelial cell The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel ...

injury, and disturbed

blood flow Hemodynamics or haemodynamics are the dynamics of blood flow. The circulatory system is controlled by homeostatic mechanisms of autoregulation, just as hydraulic circuits are controlled by control systems. The hemodynamic response continuously m ...

. Generally speaking the risk for thrombosis increases over the life course of individuals, depending on life style factors like smoking, diet, and physical activity, the presence of other diseases like cancer or autoimmune disease, while also platelet properties change in aging individuals which is an important consideration as well.

Hypercoagulability

Hypercoagulability or ''thrombophilia'', is caused by, for example,

genetic deficiencies A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...

autoimmune disorder An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...

s. Recent studies indicate that white blood cells play a pivotal role in deep vein thrombosis, mediating numerous pro-thrombotic actions.

Endothelial cell injury

Any inflammatory process, such as trauma, surgery or infection, can cause damage to the endothelial lining of the vessel's wall. The main mechanism is exposure of

tissue factor Tissue factor, also called platelet tissue factor, factor III, or CD142, is a protein encoded by the ''F3'' gene, present in subendothelial tissue and leukocytes. Its role in the clotting process is the initiation of thrombin formation from the ...

to the blood coagulation system.labtestsonline > Hypercoagulable Disorders
This article was last reviewed on May 23, 2007 and was last modified on March 6, 2010. Inflammatory and other stimuli (such as

hypercholesterolemia Hypercholesterolemia, also called high cholesterol, is the presence of high levels of cholesterol in the blood. It is a form of hyperlipidemia (high levels of lipids in the blood), hyperlipoproteinemia (high levels of lipoproteins in the blood), ...

) can lead to changes in

gene expression Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. The ...

in endothelium producing to a pro-thrombotic state. When this occurs, endothelial cells

downregulate In the biological context of organisms' production of gene products, downregulation is the process by which a cell decreases the quantity of a cellular component, such as RNA or protein, in response to an external stimulus. The complementary proc ...

substances such as

thrombomodulin Thrombomodulin (TM), CD141 or BDCA-3 is an integral membrane protein expressed on the surface of endothelial cells and serves as a cofactor for thrombin. It reduces blood coagulation by converting thrombin to an anticoagulant enzyme from a procoa ...

, which is a key modulator of thrombin activity. The result is a sustained activation of thrombin and reduced production of

protein C Protein C, also known as autoprothrombin IIA and blood coagulation factor XIX, is a zymogen, that is, an inactive enzyme. The activated form plays an important role in regulating anticoagulation, inflammation, and apoptosis, cell death and ...

and tissue factor inhibitor, which furthers the pro-thrombotic state. Endothelial injury is almost invariably involved in the formation of thrombi in arteries, as high rates of blood flow normally hinder clot formation. In addition, arterial and cardiac clots are normally rich in platelets–which are required for clot formation in areas under high stress due to blood flow.

Disturbed blood flow

Potential Mechanisms of Cancer-Related Hypercoagulability

Causes of disturbed blood flow include stagnation of blood flow past the point of injury, or

venous stasis Venostasis, or venous stasis, is a condition of slow blood flow in the veins, usually of the legs. Presentation Complications Potential complications of venous stasis are: * Venous ulcers * Blood clot formation in veins (venous thrombosis), tha ...

which may occur in

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...

, or after long periods of sedentary behaviour, such as sitting on a long airplane flight. Also, atrial fibrillation, causes stagnant blood in the left atrium (LA), or

left atrial appendage The atrium ( la, ātrium, , entry hall) is one of two upper chambers in the heart that receives blood from the circulatory system. The blood in the atria is pumped into the heart ventricles through the atrioventricular valves. There are two at ...

(LAA), and can lead to a thromboembolism.

Cancers Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Poss ...

malignancies Malignancy () is the tendency of a medical condition to become progressively worse. Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...

such as

leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...

may cause increased risk of thrombosis by possible activation of the coagulation system by cancer cells or secretion of procoagulant substances (

paraneoplastic syndrome A paraneoplastic syndrome is a syndrome (a set of signs and symptoms) that is the consequence of a tumor in the body (usually a cancerous one), specifically due to the production of chemical signaling molecules (such as hormones or cytokines) by ...

), 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). Also, treatments for cancer (radiation, chemotherapy) often cause additional hypercoagulability. There are scores that correlate different aspects of patient data (comorbidities, vital signs, and others) to risk of thrombosis, such as the POMPE-C, which stratifies risk of mortality due to pulmonary embolism in patients with cancer, who typically have higher rates of thrombosis. Also, there are several predictive scores for thromboembolic events, such as Padua, Khorana, and ThroLy score.

Pathophysiology

Natural history

Fibrinolysis Fibrinolysis is a process that prevents blood clots from growing and becoming problematic. Primary fibrinolysis is a normal body process, while secondary fibrinolysis is the breakdown of clots due to a medicine, a medical disorder, or some other c ...

is the physiological breakdown of blood clots by enzymes such as

plasmin Plasmin is an important enzyme () present in blood that degrades many blood plasma proteins, including fibrin clots. The degradation of fibrin is termed fibrinolysis. In humans, the plasmin protein (in the zymogen form of plasminogen) is encoded ...

. Organisation: following the thrombotic event, residual vascular thrombus will be re-organised histologically with several possible outcomes. For an occlusive thrombus (defined as thrombosis within a small vessel that leads to complete occlusion),

wound healing Wound healing refers to a living organism's replacement of destroyed or damaged tissue by newly produced tissue. In undamaged skin, the epidermis (surface, epithelial layer) and dermis (deeper, connective layer) form a protective barrier again ...

will reorganise the occlusive thrombus into collagenous

scar A scar (or scar tissue) is an area of fibrous tissue that replaces normal skin after an injury. Scars result from the biological process of wound repair in the skin, as well as in other organs, and tissues of the body. Thus, scarring is a na ...

tissue, where the scar tissue will either permanently obstruct the vessel, or contract down with

myofibroblast A myofibroblast is a cell phenotype that was first described as being in a state between a fibroblast and a smooth muscle cell. Structure Myofibroblasts are contractile web-like fusiform cells that are identifiable by their expression of α-sm ...

ic activity to unblock the lumen. 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

mechanism. Instead, the

platelet-derived growth factor Platelet-derived growth factor (PDGF) is one among numerous growth factors that regulate cell growth and division. In particular, PDGF plays a significant role in blood vessel formation, the growth of blood vessels from already-existing blood v ...

degranulated by the clotted

platelet Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby ini ...

s will attract a layer of

smooth muscle Smooth muscle is an involuntary non-striated muscle, so-called because it has no sarcomeres and therefore no striations (''bands'' or ''stripes''). It is divided into two subgroups, single-unit and multiunit smooth muscle. Within single-unit mus ...

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 Vasa vasorum are small blood vessels that comprise a vascular network supplying the walls of large blood vessels, such as elastic arteries (e.g., the aorta) and large veins (e.g., the venae cavae). The name derives . Occasionally two different ...

. Ischemia/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

infarction Infarction is tissue death (necrosis) due to inadequate blood supply to the affected area. It may be caused by artery blockages, rupture, mechanical compression, or vasoconstriction. The resulting lesion is referred to as an infarct (from the ...

will result. A venous thrombus may or may not be ischemic, since veins distribute deoxygenated blood that is less vital for cellular metabolism. Nevertheless, non-ischemic venous thrombosis may still be problematic, due to the swelling caused by blockage to venous drainage. In

deep vein thrombosis Deep vein thrombosis (DVT) is a type of venous thrombosis involving the formation of a blood clot in a deep vein, most commonly in the legs or pelvis. A minority of DVTs occur in the arms. Symptoms can include pain, swelling, redness, and enla ...

this manifests as pain, redness, and swelling; in

retinal vein occlusion Central retinal vein occlusion, also CRVO, is when the central retinal vein becomes occluded, usually through thrombosis. The central retinal vein is the venous equivalent of the central retinal artery and both may become occluded. Since the centra ...

this may result in

macular oedema Macular edema occurs when fluid and protein deposits collect on or under the macula of the eye (a yellow central area of the retina) and causes it to thicken and swell ( edema). The swelling may distort a person's central vision, because the macu ...

and

visual acuity Visual acuity (VA) commonly refers to the clarity of vision, but technically rates an examinee's ability to recognize small details with precision. Visual acuity is dependent on optical and neural factors, i.e. (1) the sharpness of the retinal ...

impairment, which if severe enough can lead to

blindness Visual impairment, also known as vision impairment, is a medical definition primarily measured based on an individual's better eye visual acuity; in the absence of treatment such as correctable eyewear, assistive devices, and medical treatment� ...

Embolization

A thrombus may become detached and enter circulation as an

, finally lodging in and completely obstructing a blood vessel, which unless treated very quickly will lead to tissue necrosis (an

) in the area past the occlusion. Venous thrombosis can lead to pulmonary embolism when the migrated embolus becomes lodged in the lung. In people with a "shunt" (a connection between the pulmonary and systemic circulation), either in the heart or in the lung, a venous clot can also end up in the arteries and cause arterial embolism. Arterial embolism can lead to obstruction of blood flow through the blood vessel that is obstructed by it, and a lack of oxygen and nutrients (

) of the downstream tissue. The tissue can become irreversibly damaged, a process known as

. This can affect any organ; for instance, arterial embolism of the brain is one of the causes of

Prevention

The use of

heparin Heparin, also known as unfractionated heparin (UFH), is a medication and naturally occurring glycosaminoglycan. Since heparins depend on the activity of antithrombin, they are considered anticoagulants. Specifically it is also used in the treatm ...

following surgery is common if there are no issues with bleeding. Generally, a risk-benefit analysis is required, as all anticoagulants lead to an increased risk of bleeding. 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 The Health and Social Care Select Committee (abbreviated to HSC, HSCC and HSCSC) is a Departmental Select Committee of the British House of Commons, the lower house of the United Kingdom Parliament. Its remit is to examine the policy, administr ...

heard in 2005 that the annual rate of death due to thrombosis was 25,000, with at least 50% of these being hospital-acquired. Hence ''thromboprophylaxis'' (prevention of thrombosis) is increasingly emphasized. In patients admitted for surgery, graded

compression stockings Compression stockings (Flight Socks, Support Bandage) are a specialized hosiery designed to help prevent the occurrence of, and guard against further progression of, venous disorders such as edema, phlebitis and thrombosis. Compression stockings ...

are widely used, and in severe illness, prolonged immobility and in all

orthopedic surgery Orthopedic surgery or orthopedics ( alternatively spelt orthopaedics), is the branch of surgery concerned with conditions involving the musculoskeletal system. Orthopedic surgeons use both surgical and nonsurgical means to treat musculoskeletal ...

, professional guidelines recommend

low molecular weight heparin Low-molecular-weight heparin (LMWH) is a class of anticoagulant medications. They are used in the prevention of blood clots and treatment of venous thromboembolism (deep vein thrombosis and pulmonary embolism) and in the treatment of myocardial in ...

(LMWH) administration, mechanical calf compression or (if all else is contraindicated and the patient has recently developed deep vein thrombosis) the insertion of a

vena cava filter An inferior vena cava filter is a medical device made of metal that is implanted by vascular surgeons or interventional radiologists into the inferior vena cava to prevent a life-threatening pulmonary embolism (PE) or venous thromboembolism (VTE) ...

. In patients with medical rather than surgical illness, LMWH too is known to prevent thrombosis, and in the

United Kingdom The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom (UK) or Britain, is a country in Europe, off the north-western coast of the continental mainland. It comprises England, Scotland, Wales and North ...

the

Chief Medical Officer Chief medical officer (CMO) is the title used in many countries for the senior government official designated head of medical services, sometimes at the national level. The post is held by a physician who serves to advise and lead a team of medical ...

has issued guidance to the effect that preventative measures should be used in medical patients, in anticipation of formal guidelines.

Treatment

The treatment for thrombosis depends on whether it is in a vein or an artery, the impact on the person, and the risk of complications from treatment.

Anticoagulation

Warfarin Warfarin, sold under the brand name Coumadin among others, is a medication that is used as an anticoagulant (blood thinner). It is commonly used to prevent blood clots such as deep vein thrombosis and pulmonary embolism, and to prevent strok ...

and

vitamin K antagonists Vitamin K antagonists (VKA) are a group of substances that reduce blood clotting by reducing the action of vitamin K. The term "vitamin K antagonist" is technically a misnomer, as the drugs do not directly antagonise the action of vitamin K in t ...

are

anticoagulant Anticoagulants, commonly known as blood thinners, are chemical substances that prevent or reduce coagulation of blood, prolonging the clotting time. Some of them occur naturally in blood-eating animals such as leeches and mosquitoes, where the ...

s 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 Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, vag ...

is increased, so the

international normalized ratio The prothrombin time (PT) – along with its derived measures of prothrombin ratio (PR) and international normalized ratio (INR) – is an assay for evaluating the ''extrinsic'' pathway and common pathway of coagulation. This blood test is als ...

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). Other medications such as

direct thrombin inhibitor Direct thrombin inhibitors (DTIs) are a class of medication that act as anticoagulants (delaying blood clotting) by directly inhibiting the enzyme thrombin (factor IIa). Some are in clinical use, while others are undergoing clinical development. Sev ...

s and

direct Xa inhibitor Direct factor Xa inhibitors (xabans) are anticoagulants (blood thinning drugs), used to both treat and prevent Venous thrombosis, blood clots in veins, and prevent stroke and embolism in people with atrial fibrillation (AF). Medical use Direct f ...

s are increasingly being used instead of warfarin.

Thrombolysis

Thrombolysis Thrombolysis, also called fibrinolytic therapy, is the breakdown (lysis) of blood clots formed in blood vessels, using medication. It is used in ST elevation myocardial infarction, stroke, and in cases of severe venous thromboembolism (massive p ...

is the pharmacological destruction of blood clots by administering

thrombolytic drug Thrombolysis, also called fibrinolytic therapy, is the breakdown (lysis) of blood clots formed in blood vessels, using medication. It is used in ST elevation myocardial infarction, stroke, and in cases of severe venous thromboembolism (massive ...

s including

recombinant tissue plasminogen activator Tissue plasminogen activator (abbreviated tPA or PLAT) is a protein involved in the breakdown of blood clots. It is a serine protease () found on endothelial cells, the cells that line the blood vessels. As an enzyme, it catalysis, catalyzes the c ...

, which enhances the normal destruction of blood clots by the body's enzymes. This carries an increased risk of bleeding so is generally only used for specific situations (such as severe stroke or a massive pulmonary embolism).

Surgery

Arterial thrombosis may require surgery if it causes

Endovascular treatment

Mechanical clot retrieval and catheter-guided thrombolysis are used in certain situations.

Antiplatelet agents

Arterial thrombosis is platelet-rich, and inhibition of platelet aggregation with

antiplatelet drug An antiplatelet drug (antiaggregant), also known as a platelet agglutination inhibitor or platelet aggregation inhibitor, is a member of a class of pharmaceuticals that decrease platelet aggregation and inhibit thrombus formation. They are effectiv ...

s such as

aspirin Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...

may reduce the risk of recurrence or progression.

Targeting ischemia/reperfusion injury

With reperfusion comes ischemia/reperfusion (IR) injury (IRI), which paradoxically causes cell death in reperfused tissue and contributes significantly to post-reperfusion mortality and morbidity. For example, in a feline model of intestinal ischemia, four hours of ischemia resulted in less injury than three hours of ischemia followed by one hour of reperfusion. In ST-elevation myocardial infarction (STEMI), IRI contributes up to 50% of final infarct size despite timely primary percutaneous coronary intervention. This is a key reason for the continued high mortality and morbidity in these conditions, despite endovascular reperfusion treatments and continuous efforts to improve timeliness and access to these treatments. Hence, protective therapies are required to attenuate IRI alongside reperfusion in acute ischemic conditions to improve clinical outcomes. Therapeutic strategies that have potential to improve clinical outcomes in reperfused STEMI patients include

remote ischemic conditioning Remote ischemic conditioning (RIC) is an experimental medical procedure that aims to reduce the severity of ischaemic injury to an organ such as the heart or the brain, most commonly in the situation of a heart attack or a stroke, or during proce ...

(RIC), exenatide, and metoprolol. These have emerged amongst a multitude of cardioprotective interventions investigated with largely neutral clinical data. Of these, RIC has the most robust clinical evidence, especially in the context of STEMI, but also emerging for other indications such as acute ischemic stroke and aneurysmal subarachnoid hemorrhage.

Neonatal thrombosis

Treatment options for full-term and preterm babies who develop thromboembolism include expectant management (with careful observation), nitroglycerin ointment, pharmacological therapy (thrombolytics and/or anticoagulants), and surgery. The evidence supporting these treatment approaches is weak. For anticoagulant treatment, t is not clear if unfractionated and/or low molecular weight heparin treatment is effective at decreasing mortality and serious adverse events in this population. There is also insufficient evidence to understand the risk of adverse effects associated with these treatment approaches in term or preterm infants.