Deep vein thrombosis is the formation of a blood clot ("thrombus") in a
deep veinDeep vein is a term used to describe a vein that is deep in the body. It is used to differentiate deep veins from veins which are close to the surface, also known as superficial veins....
. Deep vein thrombosis commonly affects the
legŁęg may refer to the following places in Poland:*A former name for the town of Ełk *Part of the Czyżyny district of Kraków*Łęg, Pleszew County in Greater Poland Voivodeship...
veins (such as the
femoral veinIn the human body, the femoral vein is a blood vessel that accompanies the femoral artery in the femoral sheath. It begins at the adductor canal and is a continuation of the popliteal vein...
or the
popliteal veinThe popliteal vein course runs alongside the popliteal artery but carries the blood from the knee joint and muscles in the thigh and calf back to the heart.Its origin is defined by the junction of the posterior tibial vein and anterior tibial vein....
) or the deep veins of the
pelvisIn human anatomy, the pelvis is the lower part of the trunk, between the abdomen and the lower limbs .The pelvis includes several structures:...
. Occasionally the veins of the
armIn human anatomy, the arm is the part of the upper limb between the shoulder and the elbow joints. In other animals, the term arm can also be used for analogous structures, such as one of the paired forelimbs of a four-legged animal or the arms of cephalopods...
are affected (such as in Paget-Schrötter disease). A DVT can occur without symptoms, but in many cases the affected extremity will be
painPain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...
ful,
swollenIn medical parlance, swelling is the transient enlargement or protuberance in the body and may include tumors. According to cause, it may be congenital, traumatic, inflammatory, neoplastic or miscellaneous....
, red, and warm, and the superficial veins may be engorged. The most serious complication of a DVT is that the clot could dislodge and travel to the lungs, which is called a
pulmonary embolismPulmonary embolism is a blockage of the main artery of the lung or one of its branches by a substance that has travelled from elsewhere in the body through the bloodstream . Usually this is due to embolism of a thrombus from the deep veins in the legs, a process termed venous thromboembolism...
(PE). DVT is a medical emergency, so, all limb swellings, however trivial, should be regarded as a DVT until proven otherwise. Untreated lower extremity DVT has a 3% PE-related mortality rate. Deaths associated with upper extremity DVT are extremely rare. A late complication of DVT is the
post-thrombotic syndromePost-Thrombotic Syndrome is the term used to describe signs and symptoms that may occur as long-term complications of deep vein thrombosis . It may also be referred to as post-phlebitic syndrome or venous stress disorder.-Incidence of PTS:...
, which can manifest itself as
edemaEdema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
, pain or discomfort and skin problems.
According to
Virchow's triadVirchow's triad describes the three broad categories of factors that are thought to contribute to thrombosis.*Hypercoagulability*Hemodynamic changes *Endothelial injury/dysfunction...
, venous thrombosis occurs via three mechanisms: decreased flow rate of the blood, damage to the
blood vessel wallThe endothelium is the thin layer of cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. These cells are called endothelial cells. Endothelial cells line the entire circulatory system, from the heart...
and an increased tendency of the blood to clot (hypercoagulability). Several medical conditions can lead to DVT, such as compression of the veins,
physical traumaTrauma refers to "a body wound or shock produced by sudden physical injury, as from violence or accident." It can also be described as "a physical wound or injury, such as a fracture or blow." Major trauma can result in secondary complications such as circulatory shock, respiratory failure and death...
,
cancerCancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
, infections, certain inflammatory diseases and specific conditions such as
strokeA stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
, heart failure or
nephrotic syndromeNephrotic syndrome is a nonspecific disorder in which the kidneys are damaged, causing them to leak large amounts of protein from the blood into the urine....
. There are several factors which can increase a person's risk for DVT, including
surgerySurgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...
, hospitalization, immobilization (such as when
orthopedic castAn orthopedic cast, body cast or surgical cast, is a shell, frequently made from plaster, encasing a limb to hold a broken bone in place until healing is confirmed...
s are used, or during long-haul flights, leading to traveller's thrombosis),
smokingSmoking is a practice in which a substance, most commonly tobacco or cannabis, is burned and the smoke is tasted or inhaled. This is primarily practised as a route of administration for recreational drug use, as combustion releases the active substances in drugs such as nicotine and makes them...
,
obesityObesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
, age, certain drugs (such as
estrogenEstrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
, or
erythropoietinErythropoietin, or its alternatives erythropoetin or erthropoyetin or EPO, is a glycoprotein hormone that controls erythropoiesis, or red blood cell production...
) and inborn tendencies to form clots known as
thrombophiliaThrombophilia is an abnormality of blood coagulation that increases the risk of thrombosis . Such abnormalities can be identified in 50% of people who have an episode of thrombosis that was not provoked by other causes...
(for example, in carriers of
factor V LeidenFactor V Leiden is the name given to a variant of human factor V that causes a hypercoagulability disorder. In this disorder the Leiden variant of factor V cannot be inactivated by activated protein C. Factor V Leiden is the most common hereditary hypercoagulability disorder amongst Eurasians...
). Women have an increased risk during
pregnancyPregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...
, if they are on oral contraceptives, and in the postnatal period, due to increased estrogen levels.
The most commonly used tests for the diagnosis of DVT are a
blood testA blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick....
called D-dimers and doppler ultrasound of the affected veins. Sometimes, further testing is required to find the cause of the DVT. In specific cases, an attempt can be made to break down the clot (using
thrombolytic agentsThrombolysis is the breakdown of blood clots by pharmacological means. It is colloquially referred to as clot busting for this reason...
). To prevent further accrual and formation of new clots with a risk of pulmonary embolism, anticoagulation (blood thinners) is advised (if not possible, an inferior vena cava filter may be used). Prevention of DVT is advised in many medical and surgical inpatients using anticoagulants, graduated compression stockings (also known as thromboembolic deterrent stockings) or
intermittent pneumatic compressionA therapeutic technique used in medical devices that include an air pump and inflatable auxiliary sleeves, gloves or boots in a system designed to improve venous circulation in the limbs of patients who suffer edema or the risk of deep vein thrombosis ....
(IPC) devices.
Signs and symptoms
There may be no symptoms referable to the location of the DVT, but the classical symptoms of DVT include pain, swelling and redness of the leg and dilation of the surface veins. In up to 25% of all hospitalized patients, there may be
some form of DVT, which often remains clinically inapparent (unless pulmonary embolism develops).
There are several techniques during physical examination to increase the detection of DVT, such as measuring the circumference of the affected and the contralateral limb at a fixed point (to objectivate
edemaEdema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
), and palpating the
venousIn the circulatory system, veins are blood vessels 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 blood to the heart...
tract, which is often tender. Physical examination is unreliable for excluding the diagnosis of deep vein thrombosis.
In
phlegmasia alba dolensPhlegmasia alba dolens is part of a spectrum of diseases related to deep vein thrombosis. Historically, it was commonly seen during pregnancy and in mothers who have just given birth...
, the leg is pale and cool with a diminished arterial pulse caused by spasm. It usually results from acute occlusion of the iliac and femoral veins because of DVT.
In
phlegmasia cerulea dolensPhlegmasia cerulea dolens is an uncommon severe form of deep venous thrombosis which results from extensive thrombotic occlusion of the major and the collateral veins of an extremity. It is characterized by sudden severe pain, swelling, cyanosis and edema of the affected limb...
, there is an acute and nearly total venous occlusion of the entire extremity outflow, including the iliac and femoral veins. The leg is usually painful,
cyanosedCyanosis is the appearance of a blue or purple coloration of the skin or mucous membranes due to the tissues near the skin surface being low on oxygen. The onset of cyanosis is 2.5 g/dL of deoxyhemoglobin. The bluish color is more readily apparent in those with high hemoglobin counts than it is...
(blue from lack of oxygen) and
edematousEdema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
(filled with fluid). Venous gangrene may supervene.
It is vital that the possibility of pulmonary embolism be included in the history, as this may warrant further investigation (
see pulmonary embolismPulmonary embolism is a blockage of the main artery of the lung or one of its branches by a substance that has travelled from elsewhere in the body through the bloodstream . Usually this is due to embolism of a thrombus from the deep veins in the legs, a process termed venous thromboembolism...
).
A careful history has to be taken considering
risk factors (see below), including the use of estrogen-containing methods of
hormonal contraceptionHormonal contraception refers to birth control methods that act on the endocrine system. Almost all methods are composed of steroid hormones, although in India one selective estrogen receptor modulator is marketed as a contraceptive. The original hormonal method—the combined oral contraceptive...
, recent long-haul flying, intravenous drug use and a history of
miscarriageMiscarriage or spontaneous abortion is the spontaneous end of a pregnancy at a stage where the embryo or fetus is incapable of surviving independently, generally defined in humans at prior to 20 weeks of gestation...
(which is a feature of several disorders that can also cause thrombosis). In the case of long-haul flying, recent studies have shown that risk of DVT is higher in travellers who smoke, are obese, or are currently taking contraceptive pills. A family history can reveal a
hereditaryA genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
factor in the development of DVT. Approximately 35 percent of DVT patients have at least one hereditary thrombophilia, including deficiencies in the anticoagulation factors
protein CProtein C, also known as autoprothrombin IIA and blood coagulation factor XIV, is a zymogenic protein, the activated form of which plays an important role in regulating blood clotting, inflammation, cell death and maintaining the permeability of blood vessel walls in humans and other animals...
,
protein SProtein S is a vitamin K-dependent plasma glycoprotein synthesized in the endothelium. In the circulation, Protein S exists in two forms: a free form and a complex form bound to complement protein C4b. In humans, protein S is encoded by the PROS1 gene...
,
antithrombinAntithrombin is a small protein molecule that inactivates several enzymes of the coagulation system. Antithrombin is a glycoprotein produced by the liver and consists of 432 amino acids. It contains three disulfide bonds and a total of four possible glycosylation sites...
, or mutations in the
factor VFactor V is a protein of the coagulation system, rarely referred to as proaccelerin or labile factor. In contrast to most other coagulation factors, it is not enzymatically active but functions as a cofactor...
and prothrombin genes.
Cause
The most common risk factors are recent surgery or hospitalization. 40% of these patients did not receive heparin prophylaxis. Other risk factors include advanced age, obesity, infection, immobilization, use of combined (estrogen-containing) forms of
hormonal contraceptionHormonal contraception refers to birth control methods that act on the endocrine system. Almost all methods are composed of steroid hormones, although in India one selective estrogen receptor modulator is marketed as a contraceptive. The original hormonal method—the combined oral contraceptive...
, tobacco usage and
air travelAir travel is a form of travel in vehicles such as airplanes, helicopters, hot air balloons, blimps, gliders, hang gliding, parachuting or anything else that can sustain flight.-Domestic and international flights:...
("
economy class__FORCETOC__Economy class, also called coach class , steerage, or standard class, is the lowest class of seating in air travel, rail travel, and sometimes ferry or maritime travel....
syndrome", a combination of immobility and relative dehydration). Thrombophilia (tendency to develop thrombosis) often expresses itself with recurrent thromboses.
Traveller's thrombosis
Traveller's thrombosis is the occurrence of deep vein thrombosis in travellers. The term economy class syndrome has also been used to describe this. Traveller's Thrombosis is most commonly reported in people who have travelled long distances by
aircraftA fixed-wing aircraft is an aircraft capable of flight using wings that generate lift due to the vehicle's forward airspeed. Fixed-wing aircraft are distinct from rotary-wing aircraft in which wings rotate about a fixed mast and ornithopters in which lift is generated by flapping wings.A powered...
and who are already at an increased risk of
thrombosisThrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...
. A deep venous thrombosis can lead to the fatal complication of
pulmonary embolismPulmonary embolism is a blockage of the main artery of the lung or one of its branches by a substance that has travelled from elsewhere in the body through the bloodstream . Usually this is due to embolism of a thrombus from the deep veins in the legs, a process termed venous thromboembolism...
. Although all these diseases had been recognised for a long time, the possibility of litigation against airline companies brought them into the limelight when this
syndromeIn medicine and psychology, a syndrome is the association of several clinically recognizable features, signs , symptoms , phenomena or characteristics that often occur together, so that the presence of one or more features alerts the physician to the possible presence of the others...
was reported.
The mechanism for thrombosis in travellers is probably due to a combination of immobilisation,
dehydrationIn physiology and medicine, dehydration is defined as the excessive loss of body fluid. It is literally the removal of water from an object; however, in physiological terms, it entails a deficiency of fluid within an organism...
and underlying risk factors. Additional environmental factors during air travel may also play a role. Although the problem has been specifically related to air travel, it would appear that the problem is linked to immobility and that all travellers, including travellers by bus, train and car, are equally at risk.
Patients with diseases that predispose them to thrombosis, such as
antiphospholipid syndromeAntiphospholipid syndrome or antiphospholipid antibody syndrome , often also Hughes syndrome, is an autoimmune, hypercoagulable state caused by antibodies against cell-membrane phospholipids that provokes blood clots in both arteries and veins as well as pregnancy-related complications such as...
or
cancerCancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
, are at a much greater risk. The highest risk groups include the elderly, those suffering serious medical conditions such as cancer, those with recent orthopedic surgery (legs or knees) and pregnant women. Some researchers believe that endurance-type athletes are a high risk group.
The WRIGHT (World Health Organisation Research Into Global Hazards of Travel) project has investigated the association between travel and venous thromboembolism (VTE), a term which covers deep vein thrombosis and/or
pulmonary embolismPulmonary embolism is a blockage of the main artery of the lung or one of its branches by a substance that has travelled from elsewhere in the body through the bloodstream . Usually this is due to embolism of a thrombus from the deep veins in the legs, a process termed venous thromboembolism...
(PE). This has reported that the risk of VTE approximately doubles after a long–haul flight (>4 hours) and also with other forms of travel where travellers are exposed to prolonged seated immobility. Risk increases with the duration of the travel and also in passengers having other known risk factors of VTE.
An International Consensus Statement on Traveller's Thrombosis was published in 2008.
Pathophysiology
Virchow's triad is a group of three factors known to affect clot formation: rate of flow (stasis), the consistency of the blood (high viscosity), and quality of the vessel wall (epithelial dysfunction). Virchow noted that more deep venous thrombosis occurred in the left leg than in the right and proposed compression of the left common iliac vein by the overlying right common iliac artery as the underlying cause (see
May-Thurner syndromeIn medicine, May-Thurner syndrome is a rare condition in which blood clots, called deep venous thrombosis , occur in the iliofemoral vein due to compression of the common venous outflow tract of the left lower extremity. The specific problem is compression of the left common iliac vein by the...
).
It is recognized that thrombi usually develop first in the calf veins, "growing" in the direction of flow of the vein. DVTs are distinguished as being above or below the popliteal vein. Very extensive DVTs can extend into the
iliac veinIn human anatomy, iliac vein refers to several anatomical structures located in the pelvis:*External iliac vein - terminates at the common iliac vein, drains the femoral vein....
s or the
inferior vena cavaThe inferior vena cava , also known as the posterior vena cava, is the large vein that carries de-oxygenated blood from the lower half of the body into the right atrium of the heart....
. The risk of pulmonary embolism is higher in the presence of more extensive clots.
Diagnosis
The
gold standardIn medicine and statistics, gold standard test refers to a diagnostic test or benchmark that is the best available under reasonable conditions. It does not have to be necessarily the best possible test for the condition in absolute terms...
is
intravenous venography, which involves injecting a peripheral vein of the affected limb with a contrast agent and taking
X-rayX-radiation is a form of electromagnetic radiation. X-rays have a wavelength in the range of 0.01 to 10 nanometers, corresponding to frequencies in the range 30 petahertz to 30 exahertz and energies in the range 120 eV to 120 keV. They are shorter in wavelength than UV rays and longer than gamma...
s, to reveal whether the
venousIn the circulatory system, veins are blood vessels 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 blood to the heart...
supply has been obstructed. Because of its invasiveness, this test is rarely performed.
Physical examination
Homans sign: Dorsiflexion of foot elicits pain in posterior calf.
Pratt's signPratt's sign is an indication of femoral deep vein thrombosis. It is seen as the presence of dilated pretibial veins in the affected leg, which remain dilated on raising the leg....
: Squeezing of posterior calf elicits pain.
However, these
medical signA medical sign is an objective indication of some medical fact or characteristic that may be detected by a physician during a physical examination of a patient....
s do not perform well and are not included in
clinical prediction ruleA clinical prediction rule is type of medical research study in which researchers try to identify the best combination of medical sign, symptoms, and other findings in predicting the probability of a specific disease or outcome....
s that combine best findings in order to diagnose DVT.
Probability scoring
In 2006, Scarvelis and Wells overviewed a set of
clinical prediction ruleA clinical prediction rule is type of medical research study in which researchers try to identify the best combination of medical sign, symptoms, and other findings in predicting the probability of a specific disease or outcome....
s for DVT, on the heels of a widely adopted set of clinical criteria for pulmonary embolism.
Wells score or criteria:
(Possible score -2 to 9)
- Active cancer (treatment within last 6 months or palliative) +1 point
- Calf swelling >3 cm compared to other calf (measured 10 cm below tibial tuberosity) +1 point
- Collateral superficial veins (non-varicose) +1 point
- Pitting edema (confined to symptomatic leg) +1 point
- Previous documented DVT +1 point.
- Swelling of entire leg +1 point
- Localized pain along distribution of deep venous system +1 point
- Paralysis, paresis, or recent cast immobilization of lower extremities +1 point
- Recently bedridden > 3 days, or major surgery requiring regional or general anesthetic in past 4 weeks +1 point
- Alternative diagnosis at least as likely -2 points
Interpretation:
- Score of 2 or higher — deep vein thrombosis is likely. Consider imaging the leg veins.
- Score of less than 2 — deep vein thrombosis is unlikely. Consider blood test such as d-dimer
D-dimer is a fibrin degradation product , a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis. It is so named because it contains two crosslinked D fragments of the fibrinogen protein....
test to further rule out deep vein thrombosis.
D-dimer
In a low-probability situation, current practice is to commence investigations by testing for
D-dimerD-dimer is a fibrin degradation product , a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis. It is so named because it contains two crosslinked D fragments of the fibrinogen protein....
levels. This cross-linked
fibrin degradation productFibrin degradation product , also known as fibrin split products, are components of the blood produced by clot degeneration.These are produced by the action of plasmin on deposited fibrin...
is an indication that thrombosis is occurring, and that the blood clot is being dissolved by
plasminPlasmin is an important enzyme present in blood that degrades many blood plasma proteins, most notably, fibrin clots. The degradation of fibrin is termed fibrinolysis. In humans, the plasmin protein is encoded by the PLG gene.- Function :...
. A low D-dimer level should prompt other possible diagnoses (such as a ruptured
Baker's cystA Baker's cyst, also known as a popliteal cyst, is a benign swelling of the semimembranous or more rarely some other synovial bursa found behind the knee joint. It is named after the surgeon who first described it, William Morrant Baker...
, if the patient is at sufficiently low clinical probability of DVT).
Other blood tests
Other blood tests usually performed at this point are:
- complete blood count
A complete blood count , also known as full blood count or full blood exam or blood panel, is a test panel requested by a doctor or other medical professional that gives information about the cells in a patient's blood...
- Primary coagulation
Coagulation is a complex process by which blood forms clots. It is an important part of hemostasis, the cessation of blood loss from a damaged vessel, wherein a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop bleeding and begin repair of the damaged vessel...
studies: PTThe prothrombin time and its derived measures of prothrombin ratio and international normalized ratio are measures of the extrinsic pathway of coagulation. This test is also called "ProTime INR" and "INR PT". They are used to determine the clotting tendency of blood, in the measure of warfarin...
, APTT, FibrinogenFibrinogen is a soluble plasma glycoprotein, synthesised by the liver, that is converted by thrombin into fibrin during blood coagulation. This is achieved through processes in the coagulation cascade that activate the zymogen prothrombin to the serine protease thrombin, which is responsible for...
- liver enzymes
- renal function
Renal function, in nephrology, is an indication of the state of the kidney and its role in renal physiology. Glomerular filtration rate describes the flow rate of filtered fluid through the kidney...
and electrolyteIn chemistry, an electrolyte is any substance containing free ions that make the substance electrically conductive. The most typical electrolyte is an ionic solution, but molten electrolytes and solid electrolytes are also possible....
s
Imaging
Impedance plethysmography, Doppler ultrasonography, compression ultrasound scanning of the leg veins, combined with duplex measurements (to determine blood flow), can reveal a blood clot and its extent (i.e. whether it is below or above the
kneeThe knee joint joins the thigh with the leg and consists of two articulations: one between the fibula and tibia, and one between the femur and patella. It is the largest joint in the human body and is very complicated. The knee is a mobile trocho-ginglymus , which permits flexion and extension as...
).
Duplex Ultrasonography, due to its high sensitivity, specificity and reproducibility, has replaced venography as the most widely used test in the evaluation of the disease. This test involves both a B mode image and Doppler flow analysis. It is most sensitive and specific for detecting proximal thrombi (in the popliteal and femoral veins), but substantially less so for distal thrombi (in the calf veins).
Medical inpatients
Clinical practice guidelines state:
- American College of Physicians
The American College of Physicians is a national organization of doctors of internal medicine —physicians who specialize in the prevention, detection, and treatment of illnesses in adults. With 130,000 members, ACP is the largest medical-specialty organization and second-largest physician group in...
(ACP) in 2011:
- "ACP recommends assessment of the risk for thromboembolism and bleeding in medical (including stroke) patients prior to initiation of prophylaxis of venous thromboembolism (Grade: strong recommendation, moderate-quality evidence)."
- "ACP recommends pharmacologic prophylaxis with heparin or a related drug for venous thromboembolism in medical (including stroke) patients unless the assessed risk for bleeding outweighs the likely benefits (Grade: strong recommendation, moderate-quality evidence)."
- "ACP recommends against the use of mechanical prophylaxis with graduated compression stockings for prevention of venous thromboembolism (Grade: strong recommendation, moderate-quality evidence)."
- "ACP does not support the application of performance measures in medical (including stroke) patients that promotes universal venous thromboembolism prophylaxis regardless of risk."
- American College of Chest Physicians
The American College of Chest Physicians is a medical organization in the United States consisting of physicians and non-physician specialists in the field of chest medicine, which includes pulmonology, thoracic surgery, and critical care medicine....
(ACCP) in 2008:
- "For acutely ill medical patients admitted to hospital with congestive heart failure or severe respiratory disease, or who are confined to bed and have one or more additional risk factors, including active cancer, previous VTE, sepsis
Sepsis is a potentially deadly medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection. The body may develop this inflammatory response by the immune system to microbes in the blood, urine, lungs, skin, or other tissues...
, acute neurologic disease, or inflammatory bowel disease, we recommend thromboprophylaxis with LMWH (Grade 1A), LDUH (Grade 1A), or fondaparinux (Grade 1A)."
Enoxaparin or unfractionated heparin may be used.
LMWH may be more effective than unfractionated heparin (UFH). If UFH is used, 5000 U 3 times daily may be more effective.
Since publication of the ACCP guidelines, an additional
randomized controlled trialA randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...
and
meta-analysisIn statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses. In its simplest form, this is normally by identification of a common measure of effect size, for which a weighted average might be the output of a meta-analyses. Here the...
including the trial have been published. The meta-analysis concluded " Anticoagulant prophylaxis is effective in preventing symptomatic venous thromboembolism during anticoagulant prophylaxis in at-risk hospitalized medical patients. Additional research is needed to determine the risk for venous thromboembolism in these patients after prophylaxis has been stopped." With regards to which patients are at risk, most studies in the meta-analysis were of patients with
New York Heart Association Functional ClassificationThe New York Heart Association Functional Classification provides a simple way of classifying the extent of heart failure. It places patients in one of four categories based on how much they are limited during physical activity; the limitations/symptoms are in regards to normal breathing and...
(NYHA) III-IV heart failure. Regarding patients at lesser risk of DVT, the trial above and an earlier trial are relevant yet inconclusive.
Since the ACCP guidelines,
compression stockingsCompression stockings and socks are specialised hosiery items designed to increase blood circulation. Their main theraputic purpose is to provide graduated pressure on the lower leg and foot and, in some cases, the thigh, to alleviate circulatory problems such as edema, phlebitis and...
have been studied for preventing clots in
strokeA stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
patients. In stroke patients, thigh-length stockings are more effective than knee stockings in the nonblinded CLOTS 2
randomized controlled trialA randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...
while thigh-length stockings were not better than no stockings in the CLOTS 1 nonblinded
randomized controlled trialA randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...
. It is not clear why these two trials conflict.
An effective preventative measure is early ambulation.
Chronic renal dialysis patients may be at increased risk of thromboembolism, but
randomized controlled trialA randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...
s have not addressed the risk benefit of prophylaxis.
DEFINING THE FUTURE OF DEEP VEIN THROMBOSIS (DVT) TREATMENT, the ATTRACT Study (http://www.attract.wustl.edu/) will determine if new clot-busting treatments can safely prevent post-thrombotic syndrome (PTS) and improve quality of life in patients with a blood clot in the leg. The ATTRACT Study is primarily sponsored by the National Heart Lung and Blood Institute (NHLBI).
Surgery patients
In patients who have undergone surgery,
low molecular weight heparinIn medicine, low-molecular-weight heparin is a class of medication used as an anticoagulant in diseases that feature thrombosis, as well as for prophylaxis in situations that lead to a high risk of thrombosis....
s (LMWH) are routinely administered to prevent thrombosis. LMWH can only currently be administered subcutaneously by injection. Prophylaxis for pregnant women who have a history of thrombosis may be limited to LMWH injections or may not be necessary if their risk factors are mainly temporary.
Early and regular ambulation (walking) is a treatment that predates anticoagulants and is still recognized and used today. Walking activates the body's muscle pumps, increasing venous velocity and preventing
stasisIn medicine, stasis is the state in which the normal flow of a body liquid stops, for example the flow of blood through vessels or of intestinal contents through the digestive tract....
. IPC devices have proven protective in bed- or chair-ridden patients at very high risk or with contraindications to heparins. IPC machines use air bladders that are wrapped around the thigh and/or calf. The bladders alternately inflate and deflate, squeezing the muscles and increasing blood velocity by as much as 500%. IPC machines have been proven effective on knee and hip surgery patients (a population with a risk as high as 80% with no prophylactic treatment) of developing DVT and PE.
Pregnancy
The risk of deep vein thrombosis is increased in
pregnancyPregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...
because of a physiologically adaptive mechanism of increased hypercoagulability to prevent
postpartum hemorrhageHemorrhage after delivery, or postpartum hemorrhage, is the loss of greater than 500 ml of blood following vaginal delivery, or 1000 ml of blood following cesarean section...
. However, when combined with an additional underlying hypercoagulable states, the risk of thrombosis or embolism may become substantial.
While the general consensus among physicians is that the safety of the mother supersedes the safety of the developing
fetusA fetus is a developing mammal or other viviparous vertebrate after the embryonic stage and before birth.In humans, the fetal stage of prenatal development starts at the beginning of the 11th week in gestational age, which is the 9th week after fertilization.-Etymology and spelling variations:The...
, changes in the anticoagulation regimen during pregnancy can be performed to minimize the risks to the developing fetus while maintaining therapeutic levels of anticoagulation in the mother.
The main issue with anticoagulation in pregnancy is that
warfarinWarfarin is an anticoagulant. It is most likely to be the drug popularly referred to as a "blood thinner," yet this is a misnomer, since it does not affect the thickness or viscosity of blood...
, the most commonly used anticoagulant in chronic administration, is known to have
teratogenic effectsTeratology is the study of abnormalities of physiological development. It is often thought of as the study of human birth defects, but it is much broader than that, taking in other non-birth developmental stages, including puberty; and other non-human life forms, including plants.- Etymology :The...
on the fetus if administered in early pregnancy.
Travellers
A Cochrane review in 2006 concluded that passengers can expect a substantial reduction in the incidence of symptomless DVT and leg oedema if they wear compression stockings. A randomised study in 2001 compared two sets of long haul airline passengers over the age of 50; one set wore MediUK mediven travel compression hosiery, while the other did not. The passengers were all scanned and blood tested to check for the incidence of DVT. The results showed that asymptomatic DVT occurred in 10% of the passengers who did not wear compression socks, whilst the group wearing compression had no DVTs. The authors concluded that wearing elastic compression hosiery reduces the incidence of DVT in long haul airline passengers. However it is worth noting that an
asymptomatic DVT incidence of 10% is much higher than the expected
symptomatic rate (alternatively estimated at less than 0.25%) and wearing compression stockings was also associated with
symptomatic superficial thrombophlebitis in 4%.
Plane travellers who travel on the window seat have double risk of DVT.
Prevention consists of adequate hydration (drinking, abstaining from
alcoholic beverageAn alcoholic beverage is a drink containing ethanol, commonly known as alcohol. Alcoholic beverages are divided into three general classes: beers, wines, and spirits. They are legally consumed in most countries, and over 100 countries have laws regulating their production, sale, and consumption...
s and
caffeineCaffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...
), moving around and calf muscle exercises. Any traveller with significant risk factors should seek medical advice and be considered for prophylaxis.
AspirinAspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. It was discovered by Arthur Eichengrun, a chemist with the German company Bayer...
alone is not recommended. Severe risk for thrombosis can prompt a physician to prescribe injections with
low molecular weight heparinIn medicine, low-molecular-weight heparin is a class of medication used as an anticoagulant in diseases that feature thrombosis, as well as for prophylaxis in situations that lead to a high risk of thrombosis....
(LMWH), a form of prophylaxis already in common use in hospital patients.
Anticoagulation
Anticoagulation is the usual treatment for DVT. In general, patients are initiated on a brief course (i.e., less than a week) of
heparinHeparin , also known as unfractionated heparin, a highly sulfated glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule...
treatment while they start on a 3- to 6-month course of
warfarinWarfarin is an anticoagulant. It is most likely to be the drug popularly referred to as a "blood thinner," yet this is a misnomer, since it does not affect the thickness or viscosity of blood...
(or related
vitamin KVitamin K is a group of structurally similar, fat soluble vitamins that are needed for the posttranslational modification of certain proteins required for blood coagulation and in metabolic pathways in bone and other tissue. They are 2-methyl-1,4-naphthoquinone derivatives...
inhibitors).
Low molecular weight heparinIn medicine, low-molecular-weight heparin is a class of medication used as an anticoagulant in diseases that feature thrombosis, as well as for prophylaxis in situations that lead to a high risk of thrombosis....
(LMWH) is preferred, though unfractionated
heparinHeparin , also known as unfractionated heparin, a highly sulfated glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule...
is given in patients who have a contraindication to LMWH (e.g., renal failure or imminent need for invasive procedure). In patients who have had
recurrent DVTs (two or more), anticoagulation is generally "life-long." The
Cochrane CollaborationThe Cochrane Collaboration is a group of over 28,000 volunteers in more than 100 countries who review the effects of health care interventions tested in biomedical randomized controlled trials. A few more recent reviews have also studied the results of non-randomized, observational studies...
has meta-analyzed the risk and benefits of prolonged anti-coagulation.
Once the thrombosis is treated with RBC-thinning agents, the affected area has a fair chance of returning to its normal proportions. However, thinning agents do not lessen the chance of embolism to the pulmonary or coronary arteries. Thus, while the area affected with deep venous thrombosis (i.e. the legs) may cease coagulation, pulmonary embolism is still as possible. In a 2008 Cochrane review, it was found that anticoagulation used in combination with leg compression is a more effective therapy than anticoagulation alone.
An abnormal
D-dimerD-dimer is a fibrin degradation product , a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis. It is so named because it contains two crosslinked D fragments of the fibrinogen protein....
level at the end of treatment might signal the need for continued treatment among patients with a first unprovoked proximal deep-vein thrombosis.
Despite the fact that no one disputes this, based on a meta analysis done by the Cochrane Collaboration where they found only one randomized trial of anti coagulation vs placebo in the treatment of VTE in which there was no significant difference between the two.
Current recommendations for initial treatment of acute DVT include initiation of a vitamin K antagonist (VKA) together with LMWH or UFH on the first treatment day. Heparin may be discontinued when the
international normalized ratioThe prothrombin time and its derived measures of prothrombin ratio and international normalized ratio are measures of the extrinsic pathway of coagulation. This test is also called "ProTime INR" and "INR PT". They are used to determine the clotting tendency of blood, in the measure of warfarin...
(INR) is stable and greater than 2.0. For the duration and intensity of treatment for acute DVT of the leg, the recommendations include the following:
- for patients with a first episode of DVT secondary to a transient (reversible) risk factor, long-term treatment with a VKA for 3 months.
- for patients with a first episode of idiopathic
Idiopathic is an adjective used primarily in medicine meaning arising spontaneously or from an obscure or unknown cause. From Greek ἴδιος, idios + πάθος, pathos , it means approximately "a disease of its own kind". It is technically a term from nosology, the classification of disease...
DVT, treatment with a VKA for at least 6 to 12 months. The dose of VKA is adjusted to maintain INR in the range of 2.0 to 3.0.
- for the prevention of the post-thrombotic syndrome, the use of an elastic compression stocking is recommended.
Thrombolysis
ThrombolysisThrombolysis is the breakdown of blood clots by pharmacological means. It is colloquially referred to as clot busting for this reason...
is generally reserved for extensive clot, e.g. an iliofemoral thrombosis. Although a meta-analysis of randomized controlled trials by the
Cochrane CollaborationThe Cochrane Collaboration is a group of over 28,000 volunteers in more than 100 countries who review the effects of health care interventions tested in biomedical randomized controlled trials. A few more recent reviews have also studied the results of non-randomized, observational studies...
shows improved outcomes with thrombolysis, there may be an increase in serious bleeding complications.
In July 2008, the American College of Chest Physicians (ACCP) published new evidence-based clinical guidelines for the treatment of venous thromboembolic (VTE) disease which for the first time suggested the use of pharmacomechanical thrombolysis in the treatment of certain cases of acute DVT. Complete 2008 ACCP VTE guidelines can be downloaded at no charge at:
TheNewGuidelines.org
Thrombectomy
Thrombus can be removed with a mechanical thrombectomy device. Combination therapy that uses mechanical thrombectomy to deliver localized thrombolytics has recently received considerable attention as a treatment for DVT.
Compression stockings
Elastic
compression stockingsCompression stockings and socks are specialised hosiery items designed to increase blood circulation. Their main theraputic purpose is to provide graduated pressure on the lower leg and foot and, in some cases, the thigh, to alleviate circulatory problems such as edema, phlebitis and...
should be routinely applied "beginning within 1 month of diagnosis of proximal DVT and continuing for a minimum of 1 year after diagnosis". Starting within one week may be more effective. They reduce the risk of postthrombotic syndrome. The stockings in almost all trials were
stronger than routine anti-embolism stockings and created either 20–30 mm Hg or 30–40 mm Hg. Most trials used knee-high stockings. A meta-analysis of randomized controlled trials by the
Cochrane CollaborationThe Cochrane Collaboration is a group of over 28,000 volunteers in more than 100 countries who review the effects of health care interventions tested in biomedical randomized controlled trials. A few more recent reviews have also studied the results of non-randomized, observational studies...
showed reduced incidence of post-thrombotic syndrome. The
number needed to treatThe number needed to treat is an epidemiological measure used in assessing the effectiveness of a health-care intervention, typically a treatment with medication. The NNT is the average number of patients who need to be treated to prevent one additional bad outcome...
is relatively high, at 4 to 5 patients needing to have been treated to prevent one case of post-thrombotic syndrome.
Compression Systems
Intermittent pneumatic compression (IPC) can be of benefit to patients deemed to be at risk of deep vein thrombosis. IPC is an accepted treatment method for preventing blood clots or deep venous thromboses (DVTs) and complications of venous stasis in persons after trauma, orthopaedic surgery, neurosurgery, or in disabled persons who are unable to walk or mobilise effectively.
Intermittent pneumatic compression (IPC) uses an air pump to inflate and deflate an airtight bag wrapped around the leg. This technique is also used to stop blood clots developing during surgery. However, the review of trials found conflicting evidence about whether or not IPC is better than compression bandages and hosiery. Intermittent pneumatic compression (IPC) is better for healing leg ulcers than no compression but it is uncertain if it improves healing when bandages or hosiery are already used
Inferior vena cava filter
Inferior vena cava filterAn inferior vena cava filter, also IVC filter or Greenfield Filter a type of vascular filter, is a medical device that is implanted by interventional radiologists or vascular surgeons into the inferior vena cava to prevent fatal pulmonary emboli .IVC filters are used in case of contraindication to...
reduces pulmonary embolism and is an option for patients with an absolute contraindiciation to anticoagulant treatment (e.g., cerebral hemorrhage) or those rare patients who have objectively documented recurrent PEs while on anticoagulation, an inferior vena cava filter (also referred to as a
Greenfield filter) may prevent pulmonary embolisation of the leg clot. However these filters are themselves potential of thrombosis, IVC filters are viewed as a temporizing measure for preventing life-threatening pulmonary embolism.
Hospitalization
Treatment at home is an option according to a meta-analysis by the
Cochrane CollaborationThe Cochrane Collaboration is a group of over 28,000 volunteers in more than 100 countries who review the effects of health care interventions tested in biomedical randomized controlled trials. A few more recent reviews have also studied the results of non-randomized, observational studies...
. Hospitalization should be considered in patients with more than two of the following risk factors as these patients may have more risk of complications during treatment:
- bilateral DVT
- renal insufficiency
- low body weight (<70 kg/154 lbs)
- recent immobility
- chronic heart failure
- cancer
Prognosis
In the one to two year period after the initial development of symptoms of deep vein thrombosis (DVT), post-thrombotic syndrome occurs in between as little as a fifth, and as much as half of cases. A "severe" post-thrombotic syndrome likewise varies in frequency between a twentieth and a tenth of individuals diagnosed with DVT. This malady is sometimes characterized by varicose ulceration.
Epidemiology
DVTs occur in about 1 per 1000 persons per year. It is estimated that approximately 350,000 to 600,000 Americans each year suffer from DVT and pulmonary embolism and at least 100,000 deaths may be directly or indirectly related to these diseases.
DVT is much less common in the pediatric population. About 1 in 100,000 people under the age of 18 experiences deep vein thrombosis, possibly due to a child's high rate of heartbeats per minute, relatively active lifestyle when compared with adults, and fewer
comorbiditiesIn medicine, comorbidity is either the presence of one or more disorders in addition to a primary disease or disorder, or the effect of such additional disorders or diseases.- In medicine :...
(e.g. malignancy).
In pregnant women, it has an incidence of 0.5 to 7 per 1,000 pregnancies, and is the second most common cause of
maternal deathMaternal death, or maternal mortality, also "obstetrical death" is the death of a woman during or shortly after a pregnancy. In 2010, researchers from the University of Washington and the University of Queensland in Brisbane, Australia, estimated global maternal mortality in 2008 at 342,900 , of...
in developed countries after bleeding.
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