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Deep vein thrombosis

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"DVT" redirects here. For other uses, see DVT (disambiguation).
Deep vein thrombosis
SpecialtyCardiology Edit this on Wikidata

A deep vein thrombosis (DVT) is a blood clot in a deep vein. A clot inside a blood vessel is called a thrombosis. DVTs predominantly occur in the legs and may have no symptoms. The non-specific signs of DVT include pain, swelling, redness, warmness, and engorged superficial veins in the leg. A DVT may go away naturally, but the most serious complication is when a thrombosis dislodges (embolizes) and travels to the lungs to become a life-threatening pulmonary embolism (PE). DVT and PE are the two manifestations of the disease venous thromboembolism (VTE). A late complication of DVT is the post-thrombotic syndrome, which can manifest itself as edema, pain or discomfort and skin problems. About 1 in a 1000 adults develop a DVT annually.

According to Virchow's triad, described initially in 1856 by the German pathologist Rudolph Virchow, venous thrombosis occurs due to three factors: decreased flow rate of the blood (venous stasis), damage or activation of the blood vessel wall, and an increased tendency of the blood to clot (hypercoagulability). DVT formation typically begins in the calves, inside vein valves, where the blood is relatively oxygen deprived. Several medical conditions increase the risk for DVT, such as cancer, trauma, and antiphospholipid syndrome. Other risk factors include older age (the strongest), surgery, immobilization (as with bed-rest, orthopedic casts, or during long-haul flights), oral contraceptives and inborn tendencies to form clots known as thrombophilia (for example, in carriers of factor V Leiden). Women have an increased risk during pregnancy (due to altered blood protein levels) and in the postnatal period, partially due to substances released by the placenta. However, some of those who develop DVT have no recognized risk factors.

Individuals suspected of having a DVT may receive a probability assessment, such as the Wells score, and a D-dimer test, which may exclude the diagnosis or signal further testing is needed. Diagnosis of DVT is most commonly done with ultrasound of the affected veins. Treatment for DVT is dominated by anticoagulation (which prevents further coagulation) with a heparin and a vitamin K antagonist. If anticoagulation is not possible, management may involve inferior vena cava filter placement to presumably prevent PE. A complication of DVT, post-thrombotic syndrome, appears to be reduced by wearing graduated compression stockings (GCS). Prevention of DVT is advised in at-risk medical and surgical inpatients with options such as early and frequent walking, anticoagulants, GCS or intermittent pneumatic compression (IPC).

Classification

The popliteal vein is at the top of the image.

DVT and pulmonary embolism (PE) are the two manifestations of venous thromboembolism (VTE), a term which represents a distinct disease state.[1] DVTs can be lower extremity (from the lower limbs), upper extremity, abdominal or pelvic in origin;[2] they can also occur in the neck.[3] DVTs in the legs are called proximal (or iliofemoral)[4] when above the knee and distal (or calf) when below the knee.[5][6] DVTs below the popliteal vein, a proximal vein behind the knee, are in distal calf veins.[7] Distal DVT has limited clinical significance compared to proxmial DVT.[8] An incident DVT is an initial episode and any subsequent DVTs are termed recurrent.[9] Bilateral DVT refers to a presence of thromboses in both legs while unilateral means only a single leg is affected.[10]

DVTs that have no symptoms, but are found only by screening, are labeled asymptomatic.[11] Pain and swelling are symptoms of acute DVT.[12] Acute DVTs are usually occlusive,[7] meaning they obstruct blood flow, whereas nonocclusive DVTs are more asymptomatic.[13] The label of chronic has been applied to symptomatic DVTs which persist longer than 10 or 14 days.[14] A DVT may also be called idiopathic when it "occurs in the absence of a known precipitating factor, such as oral contraceptives, surgery, trauma, or cancer."[15]

Signs and symptoms

Approximately half of people with DVT have symptoms. They include pain and tenderness in the leg, swelling, warmth in the leg that is swollen or painful, redness or discoloration, and dilation of surface veins.[16] However, signs and symptoms cannot be used to diagnose DVT. When taken together with the risk factors (see below), they are useful in determining the likelihood of DVT,[7] but most of those with suspected DVT do not have it after evaluation.[17] Most symptomatic individuals have another condition, and those possibilities include "cellulitis, Baker's cyst, musculoskeletal injury, [and] lymphedema".[18]

In phlegmasia alba dolens, which usually results from acute occlusion of the iliac and femoral veins, the leg is pale and cool with a diminished arterial pulse caused by spasm. A severe and uncommon form of DVT, phlegmasia cerulea dolens, often develops on top of a life-threatening illness.[13][19] It is characterized by an acute and nearly total venous occlusion of the entire extremity outflow, including the iliac and femoral veins. The leg is usually painful, cyanosed (blue from lack of oxygen) and edematous (filled with fluid). Venous gangrene may develop as a result.

In women, recurrent miscarriage may be a sign of DVT risk, as it is associated with antiphospholipid syndrome, a risk factor for DVT.[20]

Causes

The coagulation system, often described as a "cascade", consists of a group of proteins that interact in the formation of a fibrin-rich clot. DVT risk is increased by certain alterations in the cascade.

Venous thrombi are recognized to be caused mainly by a combination of venous stasis and hypercoagulability—but to a lesser extent endothelial damage and activation.[21] These three factors represent Virchow's triad, and changes to the vessel wall are the least understood.[22] Various risk factors increase the likelihood of any one individual developing a thrombosis. Risk factors do not predict all DVTs, however. Some of those with DVT have no risk factors present, and many individuals with multiple risk factors never have one.[23]

The strongest acquired risk factor is older age[22] due to changes in blood composition which favor clotting. Major surgery and trauma may increase DVT risk due to tissue factor from outside the vascular system mixing with blood. Cancer can grow in and around veins, causing venous stasis, and it can also stimulate increased levels of tissue factor. Pregnancy causes blood to favor clotting, and in the postpartum, hemoconcentration along with placental tearing (which releases substances that favor clotting) increase risk. Oral contraceptives and hormonal replacement therapy increase risk through a variety of mechanisms.[21] Inherited thrombophilias (deficiencies in the anticoagulation factors protein C, protein S, antithrombin, or mutations in the factor V and prothrombin genes) are present in about 30 to 50% of those with VTE.[24] Factor V Leiden and prothrombin G20210A, both predominantly expressed in Caucasians, are the most commonly inherited risk factors;[21] they moderately increase risk, by factors of about three to eight and two to three, respectively.[24][25] Deficiencies in antithrombin, protein C and S are "rare but strong risk factors for venous thrombosis."[21] These three thrombophilias increase relative risks for VTE or venous thrombosis by up to 10- or 20-fold.[23][24][26]

Depending upon their location in the body, DVTs are influenced by varying risk factors. In isolated distal DVT, the profile of risk factors appears distinct from proximal DVT; transient factors, such as surgery and immobilization, appear to dominate whereas thrombophilias and age do not seem to increase risk.[27] In upper extremity DVT, central venous catheters are a dominant risk factor.[28]

Risk factors

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The factor V protein is mutated in carriers of factor V Leiden, which is the most common inherited DVT risk factor.[33]

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Pathophysiology

The femoral vein (in the thigh), the iliac veins (in the pelvis), and the inferior vena cava (in the abdomen) are places of potential DVT extension.

DVTs usually develop first in the calf veins, and when they extend, they "grow" in the direction of venous flow, towards the knees.[34] When DVTs do not grow, they can be cleared naturally and dissolved into the blood.[35] There is a strong tendency for DVT to develop in the left leg (about 70 to 90% of the time) "possibly because of exacerbation of the compressive effects on the left iliac vein due to its being crossed by the right iliac artery."[36] DVT commonly affects the leg veins of the femoral vein, the popliteal vein, or the iliofemoral vein (as in May-Thurner syndrome). Occasionally the veins of the arm are affected, as with Paget-Schrötter disease. Very extensive lower extremity DVTs can extend into the iliac veins or the inferior vena cava. Rarer DVTs can affect the upper extremities or the mesenteric (intestinal) and pelvic veins.[2]

The mechanism behind arterial thrombosis, as with heart attacks, is more established than the steps that cause venous thrombosis.[37] With arterial thrombosis, blood vessel wall damage is required for thrombosis formation, as it initiates coagulation,[37] but the majority of venous thrombi form without any injured endothelium.[21] The initation of a venous thrombosis is thought to be caused by tissue factor effected thrombin production, which leads to fibrin deposition.[22] Red blood cells and fibrin are the main components of venous thrombi,[21] and the thrombi appear to attach to the blood vessel wall endothelium, normally a non-thrombogenic surface, with fibrin.[37] Platelets are more prominent in arterial thrombi when compared to venous thrombi.[21] In venous thrombi platelets attach to downstream fibrin, while in arterial thrombi, they compose the core.[37]

The valves of veins are a recognized site of VT initiation.[35] Due to the blood flow pattern, the base of the valve sinus is particularly deprived of oxygen (hypoxic). Stasis exacerbates hypoxia, and this state is linked to the activation of white blood cells (leukocytes) and the endothelium. Specifically, the two pathways of hypoxia-inducible factor-1 (HIF-1) and early growth response 1 (EGR-1) are activated by hypoxia, and they contribute to monocyte and endothelial activation. Hypoxia also causes reactive oxygen species (ROS) production that can activate HIF-1, EGR-1 and nuclear factor-κB (NF-κB), which regulates HIF-1 transcription.[22] HIF-1 and EGR-1 pathways lead to monocyte association with endothelial proteins, such as P-selectin, prompting monocytes to release tissue factor filled microvesicles, which presumably initiate fibrin deposition (via thrombin) after binding the endothelial surface.[22]

Diagnosis

Swelling in the leg from fluid (edema) can result in "pitting" after pressure is applied.
An ultrasound image demonstrating a blood clot in the left common femoral vein.
Abdominal CT scan showing a common iliac vein thrombosis. The arrow indicates the filling defect in the vein visualised using radiocontrast.
Venograms of DVT.

In 2012, the American College of Chest Physicians (ACCP) released their 9th edition of clinical guidelines,[38] which included recommendations on VTE diagnosis.[17] The recommendations were given strengths with "grades", depending upon the evidence for them.

Grade Description of 2012 ACCP grade[39]
1A Strong recommendation, high-quality evidence
1B Strong recommendation, moderate-quality evidence
1C Strong recommendation, low- or very-low-quality evidence
2A Weak recommendation, high-quality evidence
2B Weak recommendation, moderate-quality evidence
2C Weak recommendation, low- or very-low-quality evidence[40]

This article cites the 2012 ACCP recommendations, and it includes the grade in parentheses in this section and in the prevention and treatment sections below.

Probability

In those with suspected DVT, a clinical assessment of probability can be useful to determine which tests to perform.[41] The most studied clinical prediction rule is the Wells score.[17]

Wells score or criteria: (Possible score −2 to 9)

  1. Active cancer (treatment within last 6 months or palliative): +1 point
  2. Calf swelling ≥ 3 cm compared to asymptomatic calf (measured 10 cm below tibial tuberosity): +1 point
  3. Swollen unilateral superficial veins (non-varicose, in symptomatic leg): +1 point
  4. Unilateral pitting edema (in symptomatic leg): +1 point
  5. Previous documented DVT: +1 point
  6. Swelling of entire leg: +1 point
  7. Localized tenderness along the deep venous system: +1 point
  8. Paralysis, paresis, or recent cast immobilization of lower extremities: +1 point
  9. Recently bedridden ≥ 3 days, or major surgery requiring regional or general anesthetic in the past 12 weeks: +1 point
  10. Alternative diagnosis at least as likely: −2 points[18]

A Wells score can be interpreted in a binary (likely vs. unlikely) or ternary (low, moderate, or high probability) fashion. For a binary interpretation, scores of two or above are categorized as likely, while one and below means unlikely. For a ternary interpretation, scores of one and two are of moderate probability, while scores below or above are low and high probability, respectively.[18] When people are segregated into binary groups, DVT prevalence is about 6% versus 28%. Ternary groups stratify prevalences into groups of about 5%, 17%, and 53%.[17]

D-dimer

D-dimers are a fibrin degradation product, and a positive D-dimer test can result from the sensitive detection of a thrombosis being dissolved by plasmin. A positive test may also result from other conditions.[17] Thus, a positive D-dimer test means further diagnostic testing should be done to determine if a DVT is present, while a negative result can exclude a DVT diagnosis.[17] For suspected first lower extremity DVT in a low-probability situation, the typical next step is to test D-dimer levels with either moderate or high sensitivity.[42] In a moderate-probability scenario, the ACCP recommends a high-sensitivity D-dimer over ultrasound imaging (2C),[43] and in high-probability cases D-dimers are to be skipped in favor of diagnostic imaging.[44]

Imaging

Imaging studies are used to diagnose DVT. Ultrasound on the veins is the most common method, and the two standard options include proximal compression ultrasound or whole-leg ultrasound. Drawbacks to each method exist. A single proximal scan may miss a distal DVT, while whole-leg scanning can lead to distal DVT overtreatment.[17] Doppler ultrasound,[45] CT scan venography, MRI venography or MRI of the thrombosis are also possibilities.[17][42] The gold standard for judging imaging methods is contrast venography, which involves injecting a peripheral vein of the affected limb with a contrast agent and taking X-rays, to reveal whether the venous supply has been obstructed. Because of its cost, invasiveness, and other limitations this test is rarely performed.[17]

Prevention

Walking is a preventative measure, as are calf exercises.[46] Both reduce venous stasis. Leg muscle contractions compress the veins to pump blood up towards the heart. Blood flow patterns can also be improved in at risk immobile individuals with physical compression methods. Anticoagulation, which increases the risk of bleeding, is standard when the benefits are thought to exceed the risks. The annual risk of major bleeding from long-term anticoagulation is about 3%,[24] and the point at which annual VTE risk is thought to warrant long-term anticoagulation is estimated to be between 3 to 9%.[47] Usually, only when individuals exceed a 9% annual VTE risk is long-term anticoagulation a common consideration.[47] Antithrombin deficiency, a strong risk factor, only carries an annual risk of VTE of 0.8 to 1.5%;[24] as such, asymptomatic individuals with thrombophilia do not warrant long-term anticoagulation (1C).[48]

Surgery patients

Those who have major orthopedic surgery—such as total hip replacement, total knee replacement or hip fracture surgery—are at a high risk of VTE.[49] After any one of those three surgeries, in the absence of prophylaxis, the risk of symptomatic VTE in the 35 days after surgery is estimated to be about 4%.[50]

To prevent VTE in patients who have undergone non-orthopedic surgery, early ambulation (walking), mechanical prophylaxis (intermittent pneumatic compression [IPC] or graduated compression stockings [GCS]), and drugs (low-molecular-weight heparin [LMWH] and low-dose-unfractionated heparin [LDUH]) are potential treatments depending upon the risk of VTE, risk of major bleeding and patient preferences.[51] In major orthopedic surgery patients, the ACCP recommended additional drug options such as fondaparinux and aspirin, (1B), though LMWH is preferred (2B or 2C).[50] IPC is an option (1C).[50][52]

Pregnancy

See also: Hypercoagulability in pregnancy
Warfarin, a common VKA, is only recommended postpartum (after childbirth) in at risk women.

The risk of VTE is increased in pregnancy by about five-fold[24][36] due to a more hypercoaguable state, a likely adaptation against fatal postpartum hemorrhage.[30] Additionally, pregnant women with genetic susceptibility to blood coagulation are subject to a further and approximate three- to thirty-fold increased risk for VTE, depending upon the risk factor(s).[20] Only pregnant women with strong risk factors for VTE are suggested to receive targeted (INR of 2.0 to 3.0) preventative measures. Homozygous carriers of factor V Leiden or prothrombin G20210A with a family history of VTE were recommended by the ACCP to receive antepartum LMWH and either LMWH or a vitamin K antagonist (VKA) for the six weeks following childbirth (2B); those with another thrombophlia and a family history but no previous VTE were recommended to be subject to clinical vigilance during pregnancy and LMWH or (for those without protein C or S deficiency) a VKA (2C); homozygous carriers with no personal or family history of VTE were recommended to be subject to clinical vigilance during pregnancy and LMWH or a VKA for six weeks after childbirth (2B); and those with another thrombophilia but no family or personal history of VTE were suggested to receive clinical vigilance (2C).[20] Warfarin, a common VKA, is known to have teratogenic effects on the fetus if administered in early pregnancy[53][54] and is not advised in pregnant women.

Travellers

Graduated compression stockings are recommended in at-risk travelers and some hospital patients by the ACCP

In the 2012 ACCP clinical guidelines, grade 2C recommendations were offered. For at risk long-haul travelers—those with "previous VTE, recent surgery or trauma, active malignancy, pregnancy, estrogen use, advanced age, limited mobility, severe obesity, or known thrombophilic disorder"—recommendations for prevention included frequent walking, calf exercises, and aisle seating in airplanes to ease walking.[55][56] The use of "properly fitted, below-knee GCS providing 15 to 30 mm Hg of pressure at the ankle during travel" was recommended though use of aspirin or anticoagulants were not.[57] Compression stockings have sharply reduced the levels of asymptomatic DVT in airline passengers, but the effect on symptomatic VTE is unknown as no individuals studied developed symptomatic VTE.[58]

Hospital patients

In 2011, the American College of Physicians (ACP) issued a clinical practice guideline with three strong recommendations on moderate-quality evidence: that hospitalized patients be assessed for their risk of thromboembolism and bleeding before prophylaxis is started; that heparin or a related drug is used if potential benefits are thought to outweigh potential harms; and that graduated compression stockings not be used. The ACP also stated a lack of support for any performance measures that incentivize physicians to apply universal prophylaxis without regard to the risks.[1][59]

The 2012 ACCP guidelines include recommendations for non-surgical patients.[60][61] Anticoagulation is recommended for the acutely ill in cases of elevated risk when there is no bleeding nor a high risk of bleeding (1B).[62] When risks for both bleeding and thrombosis are elevated, mechanical prophylaxis is suggested (2C).[63] For the critically ill, prophylaxis is suggested, either pharmacological or mechanical depending upon the risk (2C).[64] In outpatients with cancer who have solid tumors and additional risk factors for VTE—listed as "previous venous thrombosis, immobilization, hormonal therapy, angiogenesis inhibitors, thalidomide, and lenalidomide"—and a low risk of bleeding, heparin is recommended (2B).[65]

Treatment

Anticoagulation

Anticoagulation, which prevents further coagulation, is the standard treatment for acute DVT of the leg. The ACCP recommends patients receive a parenteral anticoagulant (such as LMWH, fondaparinux or unfractionated heparin) for at least five days and to start vitamin K antagonist (VKA) treatment the same day (1B). The parenteral anticoagulant is recommended until the international normalized ratio (INR) is ≥ 2.0 for 24 hours minimum (1B); or, if the INR is > 3.0, the parental anticoagulant treatment can stop early.[66][67] LMWH and fondaparinux are recommended over unfractionated heparin (2B or C),[68] but unfractionated heparin does not present clearance issues in those with compromised kidney function.[67] The VKA is generally taken for a minimum of three months to maintain an INR of 2.0 to 3.0,[69][70] but the benefit of taking a VKA declines as the duration of treatment extends, while the risk of bleeding remains.[71] In those with an annual risk of venous thrombosis in excess of 9%, as after an unprovoked episode, long-term anticoagulation is a potential treatment.[47] Guidelines for anticoagulant management have been published, but many facets are understudied.[72] In those who have a positive D-dimer level after the end of VKA treatment for idiopathic VTE, there is an increased risk of recurrent VTE (about 9% vs. about 4% for negative results) and this result may be used in clinical decision making.[73]

A methodologically sound randomized controlled trial of anticoagulation versus placebo in the treatment of VTE has never been done, but it is unlikely to be performed due to ethical constraints. Evidence for clinical practice is derived from secondary evidence, such as "trials comparing anticoagulation versus placebo after initial anticoagulation."[74]

Graduated compression stockings

In addition to anticoagulation treatment, graduated compression stockings (GCSs)—which apply higher pressure (30 to 40 mm Hg) at the ankles and a lower pressure around the knees[67]—are recommended by the ACCP for those with symptomatic DVT (2B).[75] Use should begin as soon as possible after anticoagulation.[67] Randomized controlled trials indicate GCSs reduce the risk of post-thrombotic syndrome (PTS), although the "evidence is of moderate quality".[67][76] Trials do not indicate a reduction in recurrent VTE.[67] The number needed to treat is relatively high, at four to five patients needing to have been treated to prevent one case of PTS.[77] The recommended duration of use is for two years, though inconvenience and discomfort can reduce patient compliance.[75]

Inferior vena cava filter

An IVC filter

Inferior vena cava filters (IVC filters) are used on the presumption that they reduce pulmonary embolism, though their effectiveness and safety profile is not well established.[3] In general, they are recommended "to be restricted to certain high-risk situations until more information becomes available";[3] the ACCP recommended them in those with a contraindication to anticoagulant treatment (1B), but not in addition to anticoagulation (1B) unless an individual with an IVC filter, but without a risk for bleeding, develops acute proximal DVT (2B).[78] While IVC filters are "associated with an increased risk of DVT in the longer term"[3] they are not considered to be reason enough to maintain extended anticoagulation.[79]

Home vs. hospital

Home treatment is recommended by the ACCP for the initial treatment of those with acute leg DVT (1B) who feel "well enough to be treated at home (eg, [those without] severe leg symptoms or comorbidity)" as long as there is an adequate home environment, which is described as "well-maintained living conditions, strong support from family or friends, phone access, and ability to quickly return to the hospital if there is deterioration."[80]

Serial imaging

A follow-up imaging test (typically ultrasound) about one week post-diagnosis is an option for those with an acute isolated distal DVT without a high risk for extension (2C); if the thrombosis does not extend, no anticoagulation is recommended by the ACCP (1B).[67][81] This technique can benefit those at a high risk for bleeding. However, "patients who place a high value on avoiding the inconvenience of repeat imaging and a low value on the inconvenience of treatment and on the potential for bleeding are likely to choose initial anticoagulation over serial imaging."[81] When applied to symptomatic patients with a negative initial ultrasound result, serial testing is inefficient and "not cost effective."[7]

Thrombolysis and thrombectomy

Thrombolysis can be systemic or, depending upon medical capabilities, catheter-directed, but anticoagulation alone is preferred by the ACCP (2C). Although, those "who are most likely to benefit" from thrombolysis—"who attach a high value to prevention of post-thrombotic syndrome (PTS), and a lower value to the initial complexity, cost, and risk of bleeding"—"are likely to choose [it] over anticoagulation alone."[82]

A mechanical thrombectomy device can remove a thrombus. However, it is only considered as an option by the ACCP when the following conditions apply: "iliofemoral DVT, symptoms for < 7 days (criterion used in the single randomized trial), good functional status, life expectancy of ≥ 1 year, and both resources and expertise are available."[67] In general, anticoagulation alone is preferred (2C).[83]

Prognosis

The most frequent complication of proximal DVT is the post-thrombotic syndrome (PTS). Some signs and symptoms of PTS are pain, paresthesia and (in severe cases) leg ulcers. An estimated 20 to 50% of those with DVT will develop PTS, and 5 to 10% will develop severe PTS.[84] Distal DVT itself "is seldom if ever associated" with PTS or PE.[17] PE is the most serious complication of DVT, and the risk of PE is higher in the presence of more extensive clots. Untreated lower extremity DVT has a 3% PE-related mortality rate. Deaths associated with upper extremity DVT are extremely rare.[31]

Epidemiology

DVTs occur in about 1 per 1000 adults per year.[85] It is estimated that approximately 300,000 to 600,000 Americans suffer from VTE each year, with about 60,000 to 100,000 deaths attributable to PE.[86] Venous thrombosis is rare in the pediatric population, with an incidence of about 1 per 100,000 per year. From childhood to old age, incidence increases by a factor of about 1000, with almost 1% of the elderly population experiencing a venous thrombosis in a given year.[87] With pregnancy and postpartum, acute VTE incidence is about 1 per 1000 deliveries.[20] VTE develops in about 10 per 1000 people who receive preventative measures after total or partial knee replacement, and in about 5 per 1000 after total or partial hip replacement.[88]

With those who develop VTE, 30 to 50% have an inherited thrombophilia. The prevalence estimates for individual states are as follows: 0.5 to 9% for antithrombin deficiency, 3 to 9% for protein C deficiency, 1 to 3% for protein S deficiency, 12 to 20% for heterozygous factor V Leiden, 6 to 8% for heterozygous prothrombin G20210A, 0.2 to 4% for the homozygous case, and 2 to 4.5% for individuals doubly heterozygous for factor V Leiden and prothrombin G20210A.[24]

History

Rudolf Virchow

The first documented DVT is thought to have occurred in the 13th century, "in the right leg of a 20-year-old man."[23] At some point, the increased incidence of DVT in women after childbirth was noticed, and in the late 1700s, a public health recommendation was issued to encourage women to breast feed as a means to prevent this phenomenon; the DVT was called "milk leg", as it was thought to result from milk building up in the leg.[89]

In 1856, German physician and pathologist Rudolf Virchow published what is referred to as Virchow's triad, the three major causes of thrombosis.[23][89] The triad provides the theoretical framework for how venous thrombosis formation is currently explained.[23] While the medical literature can attribute the triad as explaining causation, the triad was focused on the effect of a foreign body in the venous system and the conditions required for clot propagation.[90]

Multiple pharmacological therapies for DVT were introduced in the 20th century. Oral anticoagulants were introduced in the 1940s, subcutaneous LDUH in 1962, and subcutaneous LMWH in 1982. Randomized clinical trials demonstrating the effectiveness of oral anticoagulation and subcutaneous LDUH were done in 1959 and 1972, respectively.[91] Diagnoses were commonly performed by impedance plethysmography in the 1970s and 1980s, but the use of Doppler ultrasound techniques, with their increased sensitivity and specificity, largely superseded this method.[92]

Research directions

As of 2011, three large randomized clinical trials (the Norwegian CaVent trial, the North American ATTRACT trial, and the Dutch CAVA trial) "on the effectiveness and safety of catheter directed thrombolysis" were underway.[69]

List of notable individuals

  • David Bloom, a US NBC TV journalist who died in Iraq after getting DVT and a PE[93]
  • Heavy D, a US rapper who died after a DVT and PE[94]

Notes

  1. ^ a b Qaseem A, Chou R, Humphrey LL; et al. (2011). "Venous thromboembolism prophylaxis in hospitalized patients: a clinical practice guideline from the American College of Physicians". Ann Intern Med. 155 (9): 625–32. doi:10.1059/0003-4819-155-9-201111010-00011. PMID 22041951. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  2. ^ a b Esther S.H. Kim and John R. Bartholomew. "Venous Thromboembolism". Cleveland Clinic. Retrieved 15 February 2011.
  3. ^ a b c d Young T, Tang H, Hughes R (2010). Young, Tim (ed.). "Vena caval filters for the prevention of pulmonary embolism". Cochrane Database Syst Rev (2): CD006212. doi:10.1002/14651858.CD006212.pub4. PMID 20166079.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ^ Hofmann LV, Kuo WT (2012). "Catheter-directed thrombolysis for acute DVT". Lancet. 379 (9810): 3–4. doi:10.1016/S0140-6736(11)61875-8. PMID 22172245.
  5. ^ Johnson SA, Stevens SM, Woller SC; et al. (2010). "Risk of deep vein thrombosis following a single negative whole-leg compression ultrasound: a systematic review and meta-analysis". JAMA. 303 (5): 438–45. doi:10.1001/jama.2010.43. PMID 20124539. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  6. ^ Welch 2010, p. 2.
  7. ^ a b c d Scarvelis D, Wells P (2006). "Diagnosis and treatment of deep-vein thrombosis". CMAJ. 175 (9): 1087–92. doi:10.1503/cmaj.060366. PMC 1609160. PMID 17060659. Erratum
  8. ^ Galanaud JP, Bosson JL, Quéré I (2011). "Risk factors and early outcomes of patients with symptomatic distal vs. proximal deep-vein thrombosis". Curr Opin Pulm Med. 17 (5): 387–91. doi:10.1097/MCP.0b013e328349a9e3. PMID 21832920.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  9. ^ Heit JA, Mohr DN, Silverstein MD; et al. (2000). "Predictors of recurrence after deep vein thrombosis and pulmonary embolism: a population-based cohort study". Arch Intern Med. 160 (6): 761–8. doi:10.1001/archinte.160.6.761. PMID 10737275. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  10. ^ Casella IB, Bosch MA, Sabbag CR (2009). "Incidence and risk factors for bilateral deep venous thrombosis of the lower limbs". Angiology. 60 (1): 99–103. doi:10.1177/0003319708316897. PMID 18504268.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  11. ^ Lloyd NS, Douketis JD, Moinuddin I; et al. (2008). "Anticoagulant prophylaxis to prevent asymptomatic deep vein thrombosis in hospitalized medical patients: a systematic review and meta-analysis". J Thromb Haemost. 6 (3): 405–14. doi:10.1111/j.1538-7836.2007.02847.x. PMID 18031292. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  12. ^ Conklin P, Soares GM, Dubel GJ; et al. (2009). "Acute deep vein thrombosis (DVT): evolving treatment strategies and endovascular therapy" (PDF). Med Health R I. 92 (12): 394–7. PMID 20066826. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
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References

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