Deep vein thrombosis
Deep vein thrombosis 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, 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. DVT and PE comprise the cardiovascular disease of venous thromboembolism.
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 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 the period following birth. VTE has a strong genetic component, accounting for approximately 50-60% 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 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 ≥ aged 85 annually. Asian, Asian-American, Native American, and Hispanic individuals have a lower VTE risk than white or Black people. It is more common in men than in women. 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 a blood thinner or aspirin combined with intermittent pneumatic compression.
Signs and symptoms
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 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, dilation of surface veins, warmth, discoloration, a "pulling sensation", and even cyanosis with fever. DVT can also exist without causing any symptoms. Signs and symptoms help in determining 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 in a vein close to the skin. It can co-occur with DVT and can be felt as a "palpable cord". Migratory thrombophlebitis is a noted finding in those with pancreatic cancer and is associated with DVT.
Potential complications
A pulmonary embolism occurs when a blood clot from a deep vein detaches from a vein, travels through the right side of the heart, and becomes lodged as an embolus in a pulmonary artery that supplies deoxygenated blood to 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, and fainting. The chest pain can be pleuritic 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 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 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.
Differential diagnosis
In most suspected cases, DVT is ruled out after evaluation. Cellulitis 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.Classification
DVT and PE are the two manifestations of the cardiovascular disease venous thromboembolism. 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 for more than 28 days. Differences between these two types of DVT can be seen with ultrasound. An episode of VTE after an initial one 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. DVT in a leg below the knee is termed distal DVT, 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 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 is not always clear.
Causes
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 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 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 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 increase risk. SLE itself is frequently associated with secondary antiphospholipid syndrome.
Cancer can grow in and around veins, causing venous stasis, and can also stimulate higher 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 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.
File:Coagulation in vivo.png|thumb|350px|The coagulation system, often described as a "cascade", includes a group of proteins that regulate clotting. DVT risk can be altered by abnormalities in the cascade. The regulators, antithrombin and activated protein C, are shown in green above the clotting factors they affect.|alt=Imagine showing the coagulation, which includes a group of proteins that regulate clotting. DVT risk can be altered by abnormalities in the cascade.
Dozens of genetic risk factors have been identified, and they account for approximately 50 to 60% of 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 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 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 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, cancer, and recent surgery.