Deep Vein Thrombosis


Deep vein thrombosis, or deep venous thrombosis, (DVT) is the formation of a blood clot (thrombus) in a deep vein, predominantly in the1) ___. Non-specific signs may include pain, swelling, redness, warmness, and engorged superficial veins. Pulmonary embolism, a potentially life-threatening complication, is caused by the detachment (embolization) of a clot that travels to the lungs. Together, DVT and pulmonary embolism constitute a single disease process known as venous thromboembolism. Post-thrombotic syndrome, another complication, significantly contributes to the health-care cost of DVT.


Prevention options for at-risk individuals include early and frequent walking, calf exercises, anticoagulants, aspirin, graduated compression stockings, and intermittent pneumatic compression. In 1856, German pathologist Rudolf Virchow postulated the interplay of three processes resulting in venous thrombosis, now known as Virchow’s triad: a decreased blood flow rate (venous stasis), increased tendency to clot (hypercoagulability), and changes to the blood vessel wall. DVT formation typically begins inside the valves of the calf 2) ___, where the blood is relatively oxygen deprived, which activates certain biochemical pathways. Several medical conditions increase the risk for DVT, including cancer, trauma, and antiphospholipid syndrome. Other risk factors include older age, surgery, immobilization (as with bed rest, orthopedic casts, and sitting on long flights), combined oral contraceptives, pregnancy, the postnatal period, and genetic factors such as a non-O blood type. The frequency of occurrence (incidence) increases dramatically from childhood to old 3) ___. In adulthood, about 1 in 1000 adults develops DVT annually.


Individuals suspected of having DVT may be assessed using a clinical prediction rule such as the Wells score. A D-dimer test may also be used to assist with excluding the diagnosis (because of its high sensitivity) or to signal a need for further testing. Diagnosis is most commonly done with ultrasound of the suspected veins. Anticoagulation is the standard 4) ___; typical medications include a low-molecular-weight heparin and a vitamin K antagonist. Wearing graduated compression stockings appears to reduce the risk of post-thrombotic syndrome. Common signs and symptoms of DVT include pain or tenderness, swelling, warmth, redness or discoloration, and distention of surface veins, although about half of those with the condition have no symptoms. Signs and symptoms alone are not sufficiently sensitive or specific to make a diagnosis, but when considered in conjunction with known 5) ___ factors can help determine the likelihood of DVT. In most suspected cases, DVT is ruled out after evaluation, and symptoms are more often due to other causes, such as cellulitis, Baker’s cyst, musculoskeletal injury, or lymphedema. Other differential diagnoses include hematoma, tumors, venous or arterial aneurysms, and connective tissue disorders. A severe and uncommon form of DVT, phlegmasia cerulea dolens, may develop in association with a life-threatening illness. It is characterized by an acute and almost total venous occlusion of the entire extremity outflow, including the iliac and femoral veins. The leg is usually painful, cyanosed 6) ___ (from lack of oxygen), and edematous (filled with fluid), which may result in venous gangrene.




The incision for a completed knee replacement surgery, a procedure that can predispose people to a DVT


The three factors of Virchow’s triad are: venous stasis, hypercoagulability stasis, and changes in the endothelial blood vessel lining (such as physical damage or endothelial activation) – contribute to DVT and are used to explain its formation. 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 DVT, though many at high risk never develop it. Acquired risk factors include the strong risk factor of older age, which alters blood composition to favor clotting. Other important acquired risk factors include major surgery and trauma, both of which may increase the risk because of tissue factor from outside the vascular system entering the blood. In orthopedic surgery, venous stasis may be temporarily provoked by a cessation of blood flow as part of the procedure. Cancer can grow in and around veins, causing venous stasis, and can also stimulate increased levels of tissue factor. Pregnancy causes blood to favor clotting, and in the postpartum, placental tearing releases substances that favor 7) ___. Oral contraceptives and hormonal replacement therapy increase the risk through a variety of mechanisms, including altered blood coagulation protein levels and reduced fibrinolysis.


The disease term venous thromboembolism (VTE) includes the development of either DVT or pulmonary embolism (PE). Genetic factors that increase the risk of VTE include deficiencies of three proteins that normally prevent blood from clotting – protein C, protein S, and antithrombin – in addition to non-O blood type and mutations in the factor V and prothrombin genes. Having a non-O blood type approximately doubles VTE risk. Non-O blood type is common in all races, 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. 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. In upper-extremity DVT, the most important risk factor is having a central venous catheter, and thoracic outlet syndrome also increases risk.


DVT often develops in the calf veins and “grows“ in the direction of venous flow, towards the 8) ___. When DVT does not grow, it can be cleared naturally and dissolved into the blood (fibrinolysis). Veins in the calf or thigh are most commonly affected, including the femoral vein, the popliteal vein, and the iliofemoral vein (as with May-Thurner syndrome). Extensive lower-extremity DVT can reach into the iliac vein of the pelvis or the inferior vena cava. Occasionally the veins of the arm are affected. The mechanism behind arterial thrombosis, such as with heart attacks, is more established than the steps that cause venous thrombosis. With arterial thrombosis, blood vessel wall damage is required, as it initiates coagulation, but clotting in the veins mostly occurs without any such damage.


The beginning of venous thrombosis is thought to be caused by tissue factor, which leads to conversion of prothrombin to thrombin, followed by fibrin deposition. Red blood cells and fibrin are the main components of venous thrombi, and the fibrin appears to attach to the blood vessel wall lining (endothelium), a surface that normally acts to prevent clotting. Platelets and white blood cells are also components. Platelets are not as prominent in venous clots as they are in arterial ones, but they may play a role.  Inflammation is associated with VTE, and white blood cells play a role in the formation and resolution of venous clots. 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 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.


DVT diagnosis requires the use of imaging devices such as ultrasound. Clinical assessments, which predict DVT likelihood, can help determine if a D-dimer test is useful. In those not highly likely to have DVT, a normal D-dimer result can rule out a diagnosis. Acute DVT is characterized by pain and swelling and is usually occlusive, which means that it obstructs 9) ___ flow, whereas non-occlusive DVT is less symptomatic. The label of chronic has been applied to symptomatic DVT that persists longer than 10 or 14 days. DVT that has no symptoms, but is found only by screening, is labeled asymptomatic or incidental. DVT in the legs is proximal (or iliofemoral) when above the knee and distal (or calf) when below the knee.  DVT below the popliteal vein, a proximal vein behind the knee, is classified as distal and has limited clinical significance compared to proximal DVT. An initial episode of DVT is called incident and any subsequent DVT is termed recurrent.  Bilateral DVT refers to clots in both legs while unilateral means that only a single leg is affected. For a suspected first leg DVT in a low-probability situation, the American College of Chest Physicians (ACCP) recommends testing either D-dimer levels with moderate or high sensitivity or compression ultrasound of the proximal veins. Depending upon the risk for DVT, different preventative measures are used. Walking and calf exercises reduce venous stasis because leg muscle contractions compress the veins and pump blood up towards the heart.


In 2011, three large randomized controlled trials – the Norwegian CaVent trial, the North American ATTRACT trial, and the Dutch CAVA trial – were initiated to study the effectiveness and safety of catheter-directed thrombolysis.  In 2012, two studies found a clinical benefit in taking 10) ___to prevent recurrent VTE.


ANSWERS: 1) legs; 2) veins; 3) age; 4) treatment; 5) risk; 6) blue; 7) clotting; 8) heart; 9) blood; 10) aspirin



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