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116-424: 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 enlarged veins in the affected area, but some DVTs have no symptoms. The most common life-threatening concern with DVT is the potential for a clot to embolize (detach from

232-408: A placebo medication. There is stronger evidence to suggest that LMWH helps prevent symptomatic VTE, however this treatment approach also comes with a higher risk of a major bleed compared to a placebo medication or no treatments to prevent VTE. For people who are having surgery for cancer, it is recommended that they receive anticoagulation therapy (preferably LMWH) in order to prevent a VTE. LMWH

348-484: A prediction rule such as the Wells score . A D-dimer test can also be used to assist with excluding the diagnosis or to signal a need for further testing. Diagnosis is most commonly confirmed by ultrasound of the suspected veins. VTE becomes much more common with age. The condition is rare in children, but occurs in almost 1% of those ≥ age 85 annually. Asian, Asian-American, Native American, and Hispanic individuals have

464-428: A stroke in the presence of a heart defect . This is called a paradoxical embolism because the clot abnormally travels from the pulmonary circuit to the systemic circuit while inside the heart. The defect of a patent foramen ovale is thought to allow clots to travel through the interatrial septum from the right atrium into the left atrium. In most suspected cases, DVT is ruled out after evaluation. Cellulitis

580-411: A "palpable cord". Migratory thrombophlebitis ( Trousseau's syndrome) is a noted finding in those with pancreatic cancer and is associated with DVT. A pulmonary embolism (PE) occurs when a blood clot from a deep vein (a DVT) detaches from a vein ( embolizes ), travels through the right side of the heart, and becomes lodged as an embolus in a pulmonary artery that supplies deoxygenated blood to

696-544: A 50% reduction in PE, a 70% increase in DVT, and an 18% increase in 30 day mortality when compared to no IVC placement. Other studies including a systematic review and meta-analysis did not find a difference in mortality with IVC placement. If someone develops a PE despite being anticoagulated, care should be given to optimize anticoagulation treatment and address other related concerns before considering IVC filter placement. Patients with

812-423: A D-dimer value. With this prediction rule, three points or less means a person is at low risk for DVT. A result of four or more points indicates an ultrasound is needed. Instead of using a prediction rule, experienced physicians can make a DVT pre-test probability assessment using clinical assessment and gestalt, but prediction rules are more reliable. Compression ultrasonography for suspected deep vein thrombosis

928-420: A VTE avoid medications to prevent thrombosis ( thromboprophylaxis ). For people undergoing chemotherapy for cancer that do not require a hospital stay ( those undergoing ambulatory care ), there is low certainty evidence to suggest that treatment with direct factor Xa inhibitors may help prevent symptomatic VTEs, however this treatment approach may also lead to an increase in the risk of a major bleed compared to

1044-728: A background genetic risk comparable to the factor V Leiden and prothrombin G20210A mutations. Blood alterations including dysfibrinogenemia , low free protein S, activated protein C resistance , homocystinuria , hyperhomocysteinemia , high fibrinogen levels, high factor IX levels, and high factor XI levels are associated with increased risk. Other associated conditions include heparin-induced thrombocytopenia , catastrophic antiphospholipid syndrome , paroxysmal nocturnal hemoglobinuria , nephrotic syndrome , chronic kidney disease , polycythemia vera , essential thrombocythemia , intravenous drug use, and smoking. Some risk factors influence

1160-448: A blood thinner or aspirin combined with intermittent pneumatic compression . Symptoms classically affect a leg and typically develop over hours or days, though they can develop suddenly or over a matter of weeks. The legs are primarily affected, with 4–10% of DVT occurring in the arms. Despite the signs and symptoms being highly variable, the typical symptoms are pain, swelling , and redness. However, these symptoms might not manifest in

1276-575: A condition known as varicose veins . Muscle action is needed not only to keep blood flowing through the veins but also to stimulate the lymphatic system to fulfil its "overflow" function. Long-haul flights , lengthy bed-rest , immobility caused by disability and so on, are all potential causes of water retention. Even very small exercises such as rotating ankles and wiggling toes can help to reduce it. Certain medications are prone to causing water retention. These include estrogens , thereby including drugs for hormone replacement therapy or

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1392-478: A heart-healthy lifestyle might lower their risk of venous thrombosis. Clinical policy from the American College of Physicians states a lack of support for any performance measures that incentivize physicians to apply universal prophylaxis without regard to the risks. Evidence supports the use of heparin in people following surgery who have a high risk of thrombosis to reduce the risk of DVTs; however,

1508-843: A high risk of VTE recurrence are typically anticoagulated as if they had proximal DVT. Those at a low risk for recurrence might receive a four- to six-week course of anticoagulation, lower doses, or no anticoagulation at all. In contrast, those with proximal DVT should receive at least 3 months of anticoagulation. Some anticoagulants can be taken by mouth, and these oral medicines include warfarin (a vitamin K antagonist ), rivaroxaban (a factor Xa inhibitor ), apixaban (a factor Xa inhibitor), dabigatran (a direct thrombin inhibitor ), and edoxaban (a factor Xa inhibitor). Other anticoagulants cannot be taken by mouth. These parenteral (non-oral) medicines include low-molecular-weight heparin , fondaparinux , and unfractionated heparin . Some oral medicines are sufficient when taken alone, while others require

1624-528: A high risk of bleeding, or they have active bleeding. Retrievable IVCFs are recommended if IVCFs must be used, and a plan should be created to remove the filter when it is no longer needed. While topical treatments for superficial venous thrombosis are widely used, the evidence is strongest for the heparin-like drug fondaparinux (a factor Xa inhibitor), which reduces extension and recurrence of superficial venous thrombosis as well as progression to symptomatic embolism. After an episode of unprovoked VTE,

1740-454: A higher dose of LMWH. In pregnancy, warfarin and DOACs are not considered suitable and LMWH is recommended. For those with a small pulmonary embolism and few risk factors, no anticoagulation is needed. Anticoagulation is, however, recommended in those who do have risk factors. Thrombolysis is the administration of medication (a recombinant enzyme) that activates plasmin , the body's main enzyme that breaks down blood clots. This carries

1856-438: A history of DVT might be managed by primary care , general internal medicine , hematology , cardiology , vascular surgery , or vascular medicine . Patients suspected of having an acute DVT are often referred to the emergency department for evaluation. Interventional radiology is the specialty that typically places and retrieves IVC filters, and vascular surgery might do catheter directed thrombosis for some severe DVTs. For

1972-474: A life expectancy of 1 year or more, and a low risk of bleeding." A mechanical thrombectomy device can remove DVT clots, particularly in acute iliofemoral DVT (DVT of the major veins in the pelvis), but there is limited data on its efficacy. It is usually combined with thrombolysis, and sometimes temporary IVC filters are placed to protect against PE during the procedure. Catheter-directed thrombolysis with thrombectomy against iliofemoral DVT has been associated with

2088-699: A lower VTE risk than Whites or Blacks. Populations in Asia have VTE rates at 15 to 20% of what is seen in Western countries. Using blood thinners is the standard treatment. Typical medications include rivaroxaban , apixaban , and warfarin . Beginning warfarin treatment requires an additional non-oral anticoagulant, often injections of heparin . Prevention of VTE for the general population includes avoiding obesity and maintaining an active lifestyle. Preventive efforts following low-risk surgery include early and frequent walking. Riskier surgeries generally prevent VTE with

2204-410: A lung embolism mainly if the head of the clot is poorly attached to the vein wall and is situated near the sapheno-femoral junction . When a blood clot breaks loose and travels in the blood, this is called a thromboembolism . The abbreviation DVT/PE refers to a VTE where a deep vein thrombosis (DVT) has moved to the lungs (PE or pulmonary embolism). Since the veins return blood to the heart , if

2320-589: A non-O blood type roughly doubles VTE risk. Non-O blood type is common globally, making it an important risk factor. Individuals without O blood type have higher blood levels of von Willebrand factor and factor VIII than those with O blood type, increasing the likelihood of clotting. Those homozygous for the common fibrinogen gamma gene variant rs2066865 have about a 1.6 times higher risk of VTE. The genetic variant prothrombin G20210A , which increases prothrombin levels, increases risk by about 2.5 times. Additionally, approximately 5% of people have been identified with

2436-412: A non-contrast MRI are also diagnostic possibilities. 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, availability, and other limitations, this test is rarely performed. Treatment for DVT

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2552-461: A parenteral anticoagulant together with warfarin is given, which is followed by warfarin-only therapy. Warfarin is taken to maintain an international normalized ratio (INR) of 2.0–3.0, with 2.5 as the target. The benefit of taking warfarin declines as the duration of treatment extends, and the risk of bleeding increases with age. Periodic INR monitoring is not necessary when first-line direct oral anticoagulants are used. Overall, anticoagulation therapy

2668-446: A piece of a blood clot formed in a vein breaks off it can be transported to the right side of the heart, and from there into the lungs . A piece of thrombus that is transported in this way is an embolus : the process of forming a thrombus that becomes embolic is called a thromboembolism . An embolism that lodges in the lungs is a pulmonary embolism (PE). A pulmonary embolism is a very serious condition that can be fatal depending on

2784-482: A positive D-dimer test. While the Wells score is the predominant and most studied clinical prediction rule for DVT, it does have drawbacks. The Wells score requires a subjective assessment regarding the likelihood of an alternate diagnosis and performs less well in the elderly and those with a prior DVT. The Dutch Primary Care Rule has also been validated for use. It contains only objective criteria but requires obtaining

2900-642: A prior DVT increases the risk of a subsequent DVT. Major surgery and trauma increase risk because of tissue factor from outside the vascular system entering the blood. Minor injuries, lower limb amputation, hip fracture , and long bone fractures are also risks. In orthopedic surgery , venous stasis can be temporarily provoked by a cessation of blood flow as part of the procedure. Inactivity and immobilization contribute to venous stasis, as with orthopedic casts , paralysis, sitting, long-haul travel, bed rest, hospitalization, catatonia , and in survivors of acute stroke . Conditions that involve compromised blood flow in

3016-495: A reduction in the severity of post-thrombotic syndrome at an estimated cost-effectiveness ratio of about $ 138,000 per gained QALY . Phlegmasia cerulea dolens might be treated with catheter-directed thrombolysis and/or thrombectomy. In DVT in the arm, the first (topmost) rib can be surgically removed as part of the typical treatment when the DVT is due to thoracic outlet syndrome or Paget–Schroetter syndrome . This treatment involves initial anticoagulation followed by thrombolysis of

3132-555: A result of heart failure , or local conditions such as varicose veins , thrombophlebitis , insect bites, and dermatitis . Non-pitting edema is observed when the indentation does not persist. It is associated with such conditions as lymphedema , lipedema , and myxedema . Edema caused by malnutrition defines kwashiorkor , an acute form of childhood protein-energy malnutrition characterized by edema, irritability, anorexia, ulcerating dermatoses , and an enlarged liver with fatty infiltrates. When possible, treatment involves resolving

3248-511: A risk of bleeding and is therefore reserved for those who have a form of thrombosis that may cause major complications. In pulmonary embolism, this applies in situations where heart function is compromised due to lack of blood flow through the lungs ("massive" or "high risk" pulmonary embolism), leading to low blood pressure . Deep vein thrombosis may require thrombolysis if there is a significant risk of post-thrombotic syndrome . Thrombolysis may be administered by intravenous catheter directly into

3364-602: A risk of bleeding, complexity, and the cost of the procedure. Although, while anticoagulation is the preferred treatment for DVT, thrombolysis is a treatment option for those with the severe DVT form of phlegmasia cerula dorens ( bottom left image ) and in some younger patients with DVT affecting the iliac and common femoral veins. Of note, a variety of contraindications to thrombolysis exist. In 2020, NICE kept their 2012 recommendations that catheter-directed thrombolysis should be considered in those with iliofemoral DVT who have "symptoms lasting less than 14 days, good functional status,

3480-419: A role in venous thrombi formation. NET components are pro-thrombotic through both the intrinsic and extrinsic coagulation pathways. NETs provide "a scaffold for adhesion" of platelets, red blood cells, and multiple factors that potentiate platelet activation. In addition to the pro-coagulant activities of neutrophils, multiple stimuli cause monocytes to release tissue factor. Monocytes are also recruited early in

3596-420: A role. In cancer, tissue factor is produced by cancer cells. Cancer also produces unique substances that stimulate factor Xa , cytokines that promote endothelial dysfunction , and plasminogen activator inhibitor-1 , which inhibits the breakdown of clots (fibrinolysis). Often, DVT begins in the valves of veins. The blood flow pattern in the valves can cause low oxygen concentrations in the blood ( hypoxemia ) of

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3712-425: A triple-lumen PICC line), cancer, and recent surgery. Blood has a natural tendency to clot when blood vessels are damaged ( hemostasis ) to minimize blood loss. Clotting is activated by the coagulation cascade and the clearing of clots that are no longer needed is accomplished by the process of fibrinolysis . Reductions in fibrinolysis or increases in coagulation can increase the risk of DVT. DVT often develops in

3828-629: A valve sinus. Hypoxemia, which is worsened by venous stasis, activates pathways—ones that include hypoxia-inducible factor-1 and early-growth-response protein 1 . Hypoxemia also results in the production of reactive oxygen species , which can activate these pathways, as well as nuclear factor-κB , which regulates hypoxia-inducible factor-1 transcription . Hypoxia-inducible factor-1 and early-growth-response protein 1 contribute to monocyte association with endothelial proteins, such as P-selectin , prompting monocytes to release tissue factor-filled microvesicles , which presumably begin clotting after binding to

3944-412: Is phlegmasia cerulea dolens . It is life-threatening, limb-threatening, and carries a risk of venous gangrene . Phlegmasia cerulea dolens can occur in the arm but more commonly affects the leg. If found in the setting of acute compartment syndrome , an urgent fasciotomy is warranted to protect the limb. Superior vena cava syndrome is a rare complication of arm DVT. DVT is thought to be able to cause

4060-662: Is post-thrombotic syndrome , which can cause pain, swelling, a sensation of heaviness, itching, and in severe cases, ulcers . Recurrent VTE occurs in about 30% of those in the ten years following an initial VTE. The mechanism behind DVT formation typically involves some combination of decreased blood flow , increased tendency to clot , changes to the blood vessel wall , and inflammation. Risk factors include recent surgery, older age, active cancer , obesity , infection, inflammatory diseases, antiphospholipid syndrome , personal history and family history of VTE, trauma, injuries, lack of movement, hormonal birth control , pregnancy , and

4176-453: Is a frequent mimic of DVT, with its triad of pain, swelling, and redness. Symptoms concerning for DVT are more often due to other causes, including cellulitis, ruptured Baker's cyst , hematoma , lymphedema , and chronic venous insufficiency . Other differential diagnoses include tumors, venous or arterial aneurysms , connective tissue disorders , superficial vein thrombosis , muscle vein thrombosis, and varicose veins . DVT and PE are

4292-537: Is a possibility. Those who finish warfarin treatment after idiopathic VTE with an elevated D-dimer level show an increased risk of recurrent VTE (about 9% vs about 4% for normal results), and this result might be used in clinical decision making. Thrombophilia test results rarely play a role in the length of treatment. Treatment for acute leg DVT is suggested to continue at home for uncomplicated DVT instead of hospitalization. Factors that favor hospitalization include severe symptoms or additional medical issues. Early walking

4408-427: Is classified as recurrent. Bilateral DVT refers to clots in both limbs while unilateral means only a single limb is affected. DVT in a leg above the knee is termed proximal DVT ( proximal ). DVT in a leg below the knee is termed distal DVT ( distal ), also called calf DVT when affecting the calf, and has limited clinical significance compared to proximal DVT. Calf DVT makes up about half of DVTs. Iliofemoral DVT

4524-635: Is complex, and many circumstances can affect how these therapies are managed. The duration of anticoagulation therapy (whether it will last 4 to 6 weeks, 6 to 12 weeks, 3 to 6 months, or indefinitely) is a key factor in clinical decision making . When proximal DVT is provoked by surgery or trauma a 3-month course of anticoagulation is standard. When a first VTE is proximal DVT that is either unprovoked or associated with transient non-surgical risk factor, low-dose anticoagulation beyond 3 to 6 months might be used. In those with an annual risk of VTE in excess of 9%, as after an unprovoked episode, extended anticoagulation

4640-464: Is considered "likely" (about a 28% chance), while those with a lower score are considered "unlikely" to have DVT (about a 6% chance). In those unlikely to have DVT, a diagnosis is excluded by a negative D-dimer blood test. In people with likely DVT, ultrasound is the standard imaging used to confirm or exclude a diagnosis. Imaging is also needed for hospital inpatients with suspected DVT and those initially categorized as unlikely to have DVT but who have

4756-425: Is depends on the person's height, in the average adult person, it is 8 mm Hg while lying down and 100 mm Hg while standing. In venous insufficiency, venous stasis results in abnormally high venous pressure (venous hypertension) and greater permeability of blood capillaries (capillary hyperpermeability), to drain the blood through the lymphatic system. The lymphatic system slowly removes excess fluid and proteins from

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4872-622: Is described as involving either the iliac , or common femoral vein ; elsewhere, it has been defined as involving at a minimum the common iliac vein , which is near the top of the pelvis. DVT can be classified into provoked and unprovoked categories. For example, DVT that occurs in association with cancer or surgery can be classified as provoked. However, the European Society of Cardiology in 2019 urged for this dichotomy to be abandoned to encourage more personalized risk assessments for recurrent VTE. The distinction between these categories

4988-531: Is frequently associated with secondary antiphospholipid syndrome. Cancer can grow in and around veins, causing venous stasis, and can also stimulate increased levels of tissue factor. Cancers of the blood, lung, pancreas, brain, stomach, and bowel are associated with high VTE risk. Solid tumors such as adenocarcinomas can contribute to both VTE and disseminated intravascular coagulation . In severe cases, this can lead to simultaneous clotting and bleeding. Chemotherapy treatment also increases risk. Obesity increases

5104-694: 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. 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

5220-903: Is more concerning if it starts suddenly, or pain or shortness of breath is present. Treatment depends on the underlying cause. If the underlying mechanism involves sodium retention , decreased salt intake and a diuretic may be used. Elevating the legs and support stockings may be useful for edema of the legs. Older people are more commonly affected. The word is from the Ancient Greek οἴδημα oídēma meaning 'swelling'. An edema will occur in specific organs as part of inflammations, tendinitis or pancreatitis , for instance. Certain organs develop edema through tissue specific mechanisms. Examples of edema in specific organs: A rise in hydrostatic pressure occurs in cardiac failure. A fall in osmotic pressure occurs in nephrotic syndrome and liver failure . Causes of edema that are generalized to

5336-400: Is mostly visible in the legs , feet and ankles , but water also collects in the lungs , where it causes a chronic cough . This condition is usually treated with diuretics ; otherwise, the water retention may cause breathing problems and additional stress on the heart. Another cause of severe water retention is kidney failure , where the kidneys are no longer able to filter fluid out of

5452-568: Is needed and should include a physical examination , a review of medical history , and universal cancer screening done in people of that age. A review of prior imaging is considered worthwhile, as is "reviewing baseline blood test results including full blood count , renal and hepatic function , PT and APTT ." It is not recommended practice to obtain tumor markers or a CT of the abdomen and pelvis in asymptomatic individuals. NICE recommends that further investigations are unwarranted in those without relevant signs or symptoms. Thrombolysis

5568-412: Is not always clear. Traditionally, the three factors of Virchow's triad — venous stasis , hypercoagulability , and changes in the endothelial blood vessel lining—contribute to VTE and were used to explain its formation. More recently, inflammation has been identified as playing a clear causal role. Other related causes include activation of immune system components, the state of microparticles in

5684-518: Is not well understood. With arterial thrombosis, blood vessel wall damage is required for thrombosis formation, as it initiates coagulation , but the majority of venous thrombi form without any injured epithelium. Red blood cells and fibrin are the main components of venous thrombi, and the thrombi appear to attach to the blood vessel wall endothelium , normally a non-thrombogenic surface, with fibrin. Platelets in venous thrombi attach to downstream fibrin, while in arterial thrombi, they compose

5800-529: Is overweight or obese lose weight reduce DVT risk. Avoiding both smoking and a Western pattern diet are thought to reduce risk. Statins have been investigated for primary prevention (prevention of a first VTE), and the JUPITER trial , which used rosuvastatin , has provided some tentative evidence of effectiveness. Of the statins, rosuvastatin appears to be the only one with the potential to reduce VTE risk. If so, it appears to reduce risk by about 15%. However,

5916-421: Is recommended for at least 7–10 days following cancer surgery, and for one month following surgery for people who have a high risk of VTEs. Specifically for patients with various types of lymphoma, there is a risk assessment model, ThroLy , to help providers determine how likely a thromboembolic event is to occur. American evidence-based clinical guidelines were published in 2016 for the treatment of VTE. In

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6032-427: Is seen in untreated chronic venous insufficiency and is the most common type of edema (approx. 90%). It is a combination venous/lymphatic disorder that originates in defective "leaky" veins that allows the blood to back flow ( venous reflux ), slowing the return of the blood to the heart ( venous stasis ). The venous pressure in the legs changes dramatically while standing compared to lying down. How much pressure there

6148-632: Is suggested over bedrest. Graduated compression stockings—which apply higher pressure at the ankles and a lower pressure around the knees can be trialed for symptomatic management of acute DVT symptoms, but they are not recommended for reducing the risk of post-thrombotic syndrome , as the potential benefit of using them for this goal "may be uncertain". Nor are compression stockings likely to reduce VTE recurrence. They are, however, recommended in those with isolated distal DVT. If someone decides to stop anticoagulation after an unprovoked VTE instead of being on lifelong anticoagulation, aspirin can be used to reduce

6264-399: Is termed a paradoxical embolism . When this affects the blood vessels of the brain it can cause stroke . Venous thrombi are caused mainly by a combination of venous stasis and hypercoagulability —but to a lesser extent endothelial damage and activation . The three factors of stasis, hypercoagulability, and alterations in the blood vessel wall represent Virchow's triad , and changes to

6380-683: Is the build-up of fluid in the body's tissue , a type of swelling. Most commonly, the legs or arms are affected. Symptoms may include skin that feels tight, the area feeling heavy, and joint stiffness. Other symptoms depend on the underlying cause. Causes may include venous insufficiency , heart failure , kidney problems , low protein levels , liver problems , deep vein thrombosis , infections, kwashiorkor , angioedema , certain medications, and lymphedema . It may also occur in immobile patients (stroke, spinal cord injury, aging), or with temporary immobility such as prolonged sitting or standing, and during menstruation or pregnancy . The condition

6496-410: Is the injection of an enzyme into the veins to dissolve blood clots, and while this treatment has been proven effective against the life-threatening emergency clots of stroke and heart attacks, randomized controlled trials have not established a net benefit in those with acute proximal DVT. Drawbacks of catheter-directed thrombolysis (the preferred method of administering the clot-busting enzyme) include

6612-444: Is the standard diagnostic method, and it is highly sensitive for detecting an initial DVT. A compression ultrasound is considered positive when the vein walls of normally compressible veins do not collapse under gentle pressure. Clot visualization is sometimes possible, but is not required. Three compression ultrasound scanning techniques can be used, with two of the three methods requiring a second ultrasound some days later to rule out

6728-417: Is typically either low-molecular-weight heparin (LMWH) or unfractionated heparin , or increasingly with direct acting oral anticoagulants (DOAC). Those initially treated with heparins can be switched to other anticoagulants ( warfarin , DOACs), although pregnant women and some people with cancer receive ongoing heparin treatment. Superficial venous thrombosis or phlebitis affects the superficial veins of

6844-547: Is warranted when the clots are either proximal, distal and symptomatic, or upper extremity and symptomatic. Providing anticoagulation, or blood-thinning medicine, is the typical treatment after patients are checked to make sure they are not subject to bleeding . However, treatment varies depending upon the location of DVT. For example, in cases of isolated distal DVT, ultrasound surveillance (a second ultrasound after 2 weeks to check for proximal clots), might be used instead of anticoagulation. Although, those with isolated distal DVT at

6960-481: The Wells score (see column in the table below) to determine if a potential DVT is "likely" or "unlikely" is typically the first step of the diagnostic process. The score is used in suspected first lower extremity DVT (without any PE symptoms) in primary care and outpatient settings, including the emergency department . The numerical result (possible score −2 to 9) is most commonly grouped into either "unlikely" or "likely" categories. A Wells score of two or more means DVT

7076-404: The blood and turn it into urine . Kidney disease often starts with inflammation , for instance in the case of diseases such as nephrotic syndrome or lupus . This type of water retention is usually visible in the form of swollen legs and ankles . Cirrhosis (scarring) of the liver is a common cause of edema in the legs and abdominal cavity. Phlebetic lymphedema (or phlebolymphedema)

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7192-490: The combined oral contraceptive pill , as well as non-steroidal anti-inflammatory drugs and beta-blockers . Premenstrual water retention , causing bloating and breast tenderness , is common. Six factors can contribute to the formation of edema: Generation of interstitial fluid is regulated by the forces of the Starling equation . Hydrostatic pressure within blood vessels tends to cause water to filter out into

7308-430: The enzyme protein kinase C . Edema may be described as pitting edema , or non-pitting edema . Pitting edema is when, after pressure is applied to a small area, the indentation persists after the release of the pressure. Peripheral pitting edema, as shown in the illustration, is the more common type, resulting from water retention. It can be caused by systemic diseases, pregnancy in some women, either directly or as

7424-462: The number needed to treat to prevent one initial VTE is about 2000, limiting its applicability. Acutely ill hospitalized patients are suggested to receive a parenteral anticoagulant, although the potential net benefit is uncertain. Critically ill hospitalized patients are recommended to either receive unfractionated heparin or low-molecular weight heparin instead of foregoing these medicines. Venous thrombosis The initial treatment for VTE

7540-475: The period following birth . VTE has a strong genetic component, accounting for approximately 50 to 60% of the variability in VTE rates. Genetic factors include non-O blood type , deficiencies of antithrombin , protein C , and protein S and the mutations of factor V Leiden and prothrombin G20210A . In total, dozens of genetic risk factors have been identified. People suspected of having DVT can be assessed using

7656-445: The prevention of blood clots in the general population, incorporating leg exercises while sitting down for long periods, or having breaks from a sitting position and walking around, having an active lifestyle, and maintaining a healthy body weight are recommended. Walking increases blood flow through the leg veins. Excess body weight is modifiable unlike most risk factors, and interventions or lifestyle modifications that help someone who

7772-494: The subclavian vein and staged first rib resection to relieve the thoracic outlet compression and prevent recurrent DVT. The placement of an inferior vena cava filter (IVC filter) is possible when either the standard treatment for acute DVT, anticoagulation, is absolutely contraindicated (not possible), or if someone develops a PE despite being anticoagulated. However, a 2020 NICE review found "little good evidence" for their use. A 2018 study associated IVC filter placement with

7888-709: The DOACs dabigatran , rivaroxaban , apixaban , or edoxaban rather than warfarin or low molecular weight heparin (LMWH). For those with cancer, LMWH is recommended, although DOACs appear safe in the majority of situations. For long-term treatment in people with cancer, LMWH is probably more effective at reducing VTEs when compared to vitamin K antagonists. People with cancer have a higher risk of experiencing reoccurring VTE episodes ("recurrent VTE"), even while taking preventative anticoagulation medication. These people should be given therapeutic doses of LMWH medication, either by switching from another anticoagulant or by taking

8004-594: The UK, guidelines by the National Institute for Health and Care Excellence (NICE) were published in 2012, updated in 2020. These guidelines do not cover rare forms of thrombosis, for which an individualized approach is often needed. Central and branch retinal vein occlusion does not benefit from anticoagulation in the way that other venous thromboses do. If diagnostic testing cannot be performed swiftly, many are commenced on empirical treatment. Traditionally this

8120-413: The blood, acts to temper the process of thrombus growth. This is the preferred process. Aside from the potentially deadly process of embolization, a clot can resolve through organization, which can damage the valves of veins, cause vein fibrosis, and result in non-compliant veins. Organization of a thrombus into the vein can occur at the third stage of its pathological development, in which collagen becomes

8236-425: The blood, the concentration of oxygen, and possible platelet activation. Various risk factors contribute to VTE, including genetic and environmental factors, though many with multiple risk factors never develop it. Acquired risk factors include the strong risk factor of older age, which alters blood composition to favor clotting. Previous VTE, particularly unprovoked VTE, is a strong risk factor. A leftover clot from

8352-622: The body. The excessive extracellular fluid (interstitial fluid) in edemas is to a substantial degree caused by an increased permeability of the smallest blood vessels ( capillaries ). This permeability is modulated by numerous biochemical chain reactions and can therefore be unbalanced by many influences. Involved in these processes are, among others, the transmembrane proteins occludin , claudins , tight junction protein ZO-1 , cadherins , catenins and actinin , which are directed by intracellular signal chains, in particular in connection with

8468-501: The calf veins and "grows" in the direction of venous flow, towards the heart. DVT most frequently affects veins in the leg or pelvis including the popliteal vein (behind the knee), femoral vein (of the thigh), and iliac veins of the pelvis. Extensive lower-extremity DVT can even reach into the inferior vena cava (in the abdomen). Upper extremity DVT most commonly affects the subclavian, axillary, and jugular veins . The process of fibrinolysis, where DVT clots can be dissolved back into

8584-516: The characteristic component. The first pathological stage is marked by red blood cells, and the second is characterized by medium-textured fibrin. In arterial thrombosis, blood vessel wall damage is required, as it initiates coagulation , but clotting in the veins mostly occurs without any such mechanical damage. The beginning of venous thrombosis is thought to arise from "activation of endothelial cells, platelets, and leukocytes, with initiation of inflammation and formation of microparticles that trigger

8700-412: The clot ("catheter-directed thrombolysis"); this requires a lower dose of the medication and may carry a lower bleeding risk but evidence for its benefit is limited. Inferior vena cava filters (IVCFs) are not recommended in those who are on anticoagulants. IVCFs may be used in clinical situations where a person has a high risk of experiencing a pulmonary embolism, but cannot be on anticoagulants due to

8816-531: The coagulation system" via tissue factor. Vein wall inflammation is likely the inciting event. Importantly, the activated endothelium of veins interacts with circulating white blood cells (leukocytes). While leukocytes normally help prevent blood from clotting (as does normal endothelium), upon stimulation, leukocytes facilitate clotting. Neutrophils are recruited early in the process of venous thrombi formation. They release pro-coagulant granules and neutrophil extracellular traps (NETs) or their components, which play

8932-487: The colloidal or oncotic pressure difference by allowing protein to leave the vessel more easily. Another set of vessels known as the lymphatic system acts like an "overflow" and can return much excess fluid to the bloodstream . But even the lymphatic system can be overwhelmed, and if there is simply too much fluid, or if the lymphatic system is congested, then the fluid will remain in the tissues, causing swellings in legs , ankles , feet, abdomen or any other part of

9048-403: The condition in a vicious cycle. Swollen legs , feet and ankles are common in late pregnancy . The problem is partly caused by the weight of the uterus on the major veins of the pelvis . It usually clears up after delivery of the baby, and is mostly not a cause for concern, though it should always be reported to a doctor. Lack of exercise is another common cause of water retention in

9164-434: The core. As a whole, platelets constitute less of venous thrombi when compared to arterial ones. The process is thought to be initiated by tissue factor -affected thrombin production, which leads to fibrin deposition. The valves of veins are a recognized site of VT initiation. Due to the blood flow pattern, the base of the valve sinus is particularly deprived of oxygen ( hypoxic ). Stasis exacerbates hypoxia, and this state

9280-438: The diagnosis. Whole-leg ultrasound is the option that does not require a repeat ultrasound, but proximal compression ultrasound is frequently used because distal DVT is only rarely clinically significant. Ultrasound methods including duplex and color flow Doppler can be used to further characterize the clot and Doppler ultrasound is especially helpful in the non-compressible iliac veins. CT scan venography , MRI venography, or

9396-414: The dimensions of the embolus. While venous thrombosis of the legs is the most common form, venous thrombosis may occur in other veins. These may have particular specific risk factors: Systemic embolism of venous origin can occur in patients with an atrial or ventricular septal defect , or an arteriovenous connection in the lung, through which an embolus may pass into the arterial system. Such an event

9512-432: The edema may occur before there is any significant protein in the urine ( proteinuria ) or fall in plasma protein level. Most forms of nephrotic syndrome are due to biochemical and structural changes in the basement membrane of capillaries in the kidney glomeruli, and these changes occur, if to a lesser degree, in the vessels of most other tissues of the body. Thus the resulting increase in permeability that leads to protein in

9628-494: The effect on PEs or overall mortality is not known. In hospitalized non-surgical patients, mortality does not appear to change. It does not appear, however, to decrease the rate of symptomatic DVTs. Using both heparin and compression stockings appears better than either one alone in reducing the rate of DVT. In hospitalized people who have had a stroke and not had surgery, mechanical measures ( compression stockings ) resulted in skin damage and no clinical improvement. Data on

9744-465: The effectiveness of compression stockings among hospitalized non-surgical patients without stroke is scarce. The American College of Physicians (ACP) gave three strong recommendations with moderate quality evidence on VTE prevention in non-surgical patients: In adults who have had their lower leg casted, braced, or otherwise immobilized for more than a week, LMWH may decrease the risk and severity of deep vein thrombosis, but does not have any effect on

9860-478: The endothelial surface. D-dimers are a fibrin degradation product , a natural byproduct of fibrinolysis that is typically found in the blood. An elevated level can result from plasmin dissolving a clot—or other conditions. Hospitalized patients often have elevated levels for multiple reasons. Anticoagulation , the standard treatment for DVT, prevents further clot growth and PE, but does not act directly on existing clots. A clinical probability assessment using

9976-484: The endothelial surface. Numerous medications have been shown to reduce the risk of a person having a VTE, however careful decision making is required in order to decide if a person's risk of having a VTE outweighs the risks associated with most thromboprophylaxis treatment approaches (medications to prevent venous thrombosis). It is recommended that people should be assessed at their hospital discharge for persistent high-risk of venous thrombosis and that people who adopt

10092-429: The gastrointestinal organs), cerebral venous sinus thrombosis , renal vein thrombosis , and ovarian vein thrombosis. Superficial venous thromboses cause discomfort but generally not serious consequences, as do the deep vein thromboses (DVTs) that form in the deep veins of the legs or in the pelvic veins. Nevertheless, they can progress to the deep veins through the perforator veins or, they can be responsible for

10208-444: The highest incidence rate is found among those ≥70 years of age (390 per 100,000 in men and 370 per 100,000 in women), whereas the highest incidence ratios compared to those without affected siblings occurred at much younger ages (ratio of 4.3 among men 20 to 29 years of age and 5.5 among women 10 to 19 years of age). In contrast to the understanding for how arterial thromboses occur, as with heart attacks , venous thrombosis formation

10324-435: The incidence of pulmonary embolism . Following the completion of warfarin in those with prior VTE, the use of long-term aspirin has been shown to be beneficial. People who have cancer have a higher risk of VTE and may respond differently to anticoagulant preventative treatments and prevention measures. The American Society of Hematology strongly suggests that people undergoing chemotherapy for cancer who are at low risk of

10440-401: The legs. Exercise helps the leg veins work against gravity to return blood to the heart . If blood travels too slowly and starts to pool in the leg veins , the pressure can force too much fluid out of the leg capillaries into the tissue spaces. The capillaries may break, leaving small blood marks under the skin . The veins themselves can become swollen, painful and distorted –

10556-421: The likelihood of DVT, but they are not used alone for diagnosis. At times, DVT can cause symptoms in both arms or both legs, as with bilateral DVT. Rarely, a clot in the inferior vena cava can cause both legs to swell. Superficial vein thrombosis , also known as superficial thrombophlebitis , is the formation of a blood clot (thrombus) in a vein close to the skin . It can co-occur with DVT and can be felt as

10672-408: The location of DVT within the body. 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. Common risk factors for having an upper extremity DVT include having an existing foreign body (such as a central venous catheter, a pacemaker, or

10788-556: The lower limbs of those unable to walk. In those who are able to walk, DVT can reduce one's ability to do so. The pain can be described as throbbing and can worsen with weight-bearing, prompting one to bear more weight with the unaffected leg. Additional signs and symptoms include tenderness, pitting edema ( see image ), dilation of surface veins, warmth, discoloration, a "pulling sensation", and even cyanosis (a blue or purplish discoloration) with fever. DVT can also exist without causing any symptoms. Signs and symptoms help in determining

10904-453: The lower part of the leg, usually from the calf down. Hydrops fetalis is a condition in a baby characterized by an accumulation of fluid in at least two body compartments. The pumping force of the heart should help to keep a normal pressure within the blood vessels . But if the heart begins to fail (a condition known as congestive heart failure ) the pressure changes can cause very severe water retention. In this condition water retention

11020-565: The lungs for oxygenation. Up to one-fourth of PE cases are thought to result in sudden death. When not fatal, PE can cause symptoms such as sudden onset shortness of breath or chest pain , coughing up blood ( hemoptysis ), and fainting ( syncope ). The chest pain can be pleuritic (worsened by deep breaths) and can vary based upon where the embolus is lodged in the lungs. An estimated 30–50% of those with PE have detectable DVT by compression ultrasound . A rare and massive DVT that causes significant obstruction and discoloration (including cyanosis)

11136-422: The potential of blood to clot, as does pregnancy. In the postpartum , placental tearing releases substances that favor clotting. Oral contraceptives and hormonal replacement therapy increase the risk through a variety of mechanisms, including altered blood coagulation protein levels and reduced fibrinolysis . Dozens of genetic risk factors have been identified, and they account for approximately 50 to 60% of

11252-413: The process. Tissue factor, via the tissue factor– factor VIIa complex, activates the extrinsic pathway of coagulation and leads to conversion of prothrombin to thrombin, followed by fibrin deposition. Fresh venous clots are red blood cell and fibrin rich. Platelets and white blood cells are also components. Platelets are not as prominent in venous clots as they are in arterial ones, but they can play

11368-401: The risk of further episodes after completing treatment remains elevated, although this risk diminishes over time. Over ten years, 41% of men and 29% of women can expect to experience a further episode. For each episode, the risk of death is 4%. Edema Edema ( American English ), also spelled oedema ( British English ), and also known as fluid retention , dropsy and hydropsy ,

11484-408: The risk of recurrence, but it is only about 33% as effective as anticoagulation in preventing recurrent VTE. Statins have also been investigated for their potential to reduce recurrent VTE rates, with some studies suggesting effectiveness. An unprovoked VTE might signal the presence of an unknown cancer, as it is an underlying condition in up to 10% of unprovoked cases. A thorough clinical assessment

11600-480: The route of administration of UFH ( subcutaneous or intravenous ). LMWH is usually administered by a subcutaneous injection , and a person's blood clotting factors do not have to be monitored as closely as with UFH. Once the diagnosis is confirmed, a decision needs to be made about the nature of the ongoing treatment and its duration. USA recommendations for those without cancer include anticoagulation (medication that prevents further blood clots from forming) with

11716-499: The same dose of estrogen and duration of use, the rate ratio of deep vein thrombosis for combined oral contraceptives with norethisterone is 0.98, with norgestimate 1.19, with desogestrel (DSG) 1.82, with gestodene 1.86, with drospirenone (DRSP) 1.64, and with cyproterone acetate 1.88. Venous thromboembolism occurs in 100–200 per 100,000 pregnant women every year. Regarding family history, age has substantial effect modification . For people with two or more affected siblings,

11832-403: The tissue. This leads to a difference in protein concentration between blood plasma and tissue. As a result, the colloidal or oncotic pressure of the higher level of protein in the plasma tends to draw water back into the blood vessels from the tissue. Starling's equation states that the rate of leakage of fluid is determined by the difference between the two forces and also by the permeability of

11948-573: The two manifestations of the cardiovascular disease venous thromboembolism (VTE). VTE can occur as DVT only, DVT with PE, or PE only. About two-thirds of VTE manifests as DVT only, with one-third manifesting as PE with or without DVT. VTE, along with superficial vein thrombosis, are common types of venous thrombosis. DVT is classified as acute when the clots are developing or have recently developed, whereas chronic DVT persists more than 28 days. Differences between these two types of DVT can be seen with ultrasound. An episode of VTE after an initial one

12064-451: The underlying cause. Many cases of heart or kidney disease are treated with diuretics . Treatment may also involve positioning the affected body parts to improve drainage. For example, swelling in feet or ankles may be reduced by having the person lie down in bed or sit with the feet propped up on cushions. Intermittent pneumatic compression can be used to pressurize tissue in a limb, forcing fluids—both blood and lymph —to flow out of

12180-472: The upper or lower extremity and only require anticoagulation in specific situations, and may be treated with anti-inflammatory pain relief only. There are other less common forms of venous thrombosis, some of which can also lead to pulmonary embolism. Venous thromboembolism and superficial vein thrombosis account for about 90% of venous thrombosis. Other rarer forms include retinal vein thrombosis , mesenteric vein thrombosis (affecting veins draining blood from

12296-548: The urine can explain the edema if all other vessels are more permeable as well. As well as the previously mentioned conditions, edemas often occur during the late stages of pregnancy in some women. This is more common with those of a history of pulmonary problems or poor circulation also being intensified if arthritis is already present in that particular woman. Women who already have arthritic problems most often have to seek medical help for pain caused from over-reactive swelling. Edemas that occur during pregnancy are usually found in

12412-412: The use of an additional parenteral blood thinner. Rivaroxaban and apixaban are the typical first-line medicines, and they are sufficient when taken orally. Rivaroxaban is taken once daily, and apixaban is taken twice daily. Warfarin, dabigatran, and edoxaban require the use of a parenteral anticoagulant to initiate oral anticoagulant therapy. When warfarin is initiated for VTE treatment, a 5-day minimum of

12528-545: The variability in VTE rates. As such, family history of VTE is a risk factor for a first VTE. Factor V Leiden , which makes factor V resistant to inactivation by activated protein C , mildly increases VTE risk by about three times. Deficiencies of three proteins that normally prevent blood from clotting— protein C , protein S , and antithrombin —contribute to VTE. These deficiencies in antithrombin , protein C , and protein S are rare but strong, or moderately strong, risk factors. They increase risk by about 10 times. Having

12644-556: The veins are May–Thurner syndrome , where a vein of the pelvis is compressed, and venous thoracic outlet syndrome , which includes Paget–Schroetter syndrome , where compression occurs near the base of the neck. Infections, including sepsis , COVID-19 , HIV , and active tuberculosis , increase risk. Chronic inflammatory diseases and some autoimmune diseases , such as inflammatory bowel disease , systemic sclerosis , Behçet's syndrome , primary antiphospholipid syndrome , and systemic lupus erythematosus (SLE) increase risk. SLE itself

12760-436: The veins in the lower legs towards the upper body; however, as it is not as efficient as an unimpaired circulatory system, swelling (edema) is visible, particularly in the ankles and lower leg. The chronic increased fluid in the lymphatic system and capillary hyperpermeability causes an inflammatory response which leads to tissue fibrosis of both veins and lymphatic system, opening of arteriovenous shunts, all of which then worsens

12876-427: The veins), travel as an embolus through the right side of the heart, and become lodged in a pulmonary artery that supplies blood to the lungs . This is called a pulmonary embolism (PE). DVT and PE comprise the cardiovascular disease of venous thromboembolism (VTE). About two-thirds of VTE manifests as DVT only, with one-third manifesting as PE with or without DVT. The most frequent long-term DVT complication

12992-472: The vessel wall are the least understood. Various risk factors increase the likelihood of any one individual developing a thrombosis: The overall absolute risk of venous thrombosis per 100,000 woman years in current use of combined oral contraceptives is approximately 60, compared to 30 in non-users. The risk of thromboembolism varies with different types of birth control pills; Compared with combined oral contraceptives containing levonorgestrel (LNG), and with

13108-583: The vessel wall open up then permeability to water is increased first, but as the gaps increase in size permeability to protein also increases with a fall in reflection coefficient. Changes in the variables in Starling's equation can contribute to the formation of edemas either by an increase in hydrostatic pressure within the blood vessel, a decrease in the oncotic pressure within the blood vessel or an increase in vessel wall permeability. The latter has two effects. It allows water to flow more freely and it reduces

13224-404: The vessel wall to water, which determines the rate of flow for a given force imbalance. Most water leakage occurs in capillaries or post capillary venules , which have a semi-permeable membrane wall that allows water to pass more freely than protein. (The protein is said to be reflected and the efficiency of reflection is given by a reflection constant of up to 1.) If the gaps between the cells of

13340-429: The whole body can cause edema in multiple organs and peripherally. For example, severe heart failure can cause pulmonary edema , pleural effusions, ascites and peripheral edema . Such severe systemic edema is called anasarca . In rare cases, a parvovirus B19 infection may cause generalized edemas. Although a low plasma oncotic pressure is widely cited for the edema of nephrotic syndrome, most physicians note that

13456-469: Was heparin, but several of the DOACs are licensed for treatment without initial heparin use. If heparin is used for initial treatment of VTE, fixed doses with low-molecular-weight heparin (LMWH) may be more effective than adjusted doses of unfractionated heparin (UFH) in reducing blood clots. No differences in mortality, prevention of major bleeding, or preventing VTEs from recurring were observed between LMWH and UFH. No differences have been detected in

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