500px 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<unk> .<unk>  often develops in the calf<unk> s and "grows" in the direction of venous flow, towards the heart.<unk>  most frequently affects<unk> s in the leg or pelvis including the popliteal<unk>  (behind the knee), femoral<unk>  (of the thigh), and iliac<unk> s of the pelvis. Extensive lower-extremity<unk>  can even reach into the inferior vena cava (in the abdomen). Upper extremity<unk>  most commonly affects the subclavian, axillary, and jugular<unk> s. The process of fibrinolysis, where<unk>  clots can be dissolved back into 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<unk> s, cause<unk>  fibrosis, and result in non-compliant<unk> s. Organization of a thrombus into the<unk>  can occur at the third stage of its pathological development, in which collagen becomes the characteristic component. The first pathological stage is marked by red blood cells, and the second is characterized by medium-textured fibrin. jugular and brachiocephalic<unk> s (not pictured). The cephalic and basilic<unk> s, however, are superficial<unk> s.|alt=An image showing major arm<unk> s In arterial thrombosis, blood vessel wall damage is required, as it initiates coagulation, but clotting in the<unk> s 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 the coagulation system" via tissue factor.<unk>  wall inflammation is likely the inciting event. Importantly, the activated endothelium of<unk> s 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 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 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 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). alt=Image depicting D-dimer production Often,<unk>  begins in the valves of<unk> s. 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. 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 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<unk> , prevents further clot growth and PE, but does not act directly on existing clots. Diagnosis A clinical probability assessment using the Wells score (see dedicated column in the table below) to determine if a potential<unk>  is "likely" or "unlikely" is typically the first step of the diagnostic process. The score is used in suspected first lower extremity<unk>  (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<unk>  is considered "likely" (about a 28% chance), while those with a lower score are considered "unlikely" to have<unk>  (about a 6% chance). In those unlikely to have<unk> , a diagnosis is excluded by a negative D-dimer blood test. In people with likely<unk> , ultrasound is the standard imaging used to confirm or exclude a diagnosis. Imaging is also needed for hospital inpatients with suspected<unk>  and those initially categorized as unlikely to have<unk>  but who have a positive D-dimer test. While the Wells score is the predominant and most studied clinical prediction rule for<unk> , 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<unk> . The Dutch Primary Care Rule has also been validated for use. It contains only objective criteria but requires obtaining a D-dimer value. With this prediction rule, three points or less means a person is at low risk for<unk> . A result of four or more points indicates an ultrasound is needed. Instead of using a prediction rule, experienced physicians can make a<unk>  pre-test probability assessment using clinical assessment and gestalt, but prediction rules are more reliable. Criteria Wells score for<unk>  Dutch Primary Care Rule Active cancer (treatment within last 6 months or palliative) +1 point +1 point Calf swelling ≥ 3 cm compared to asymptomatic calf (measured 10 cm below tibial tuberosity) +1 point +2 points Swollen unilateral superficial<unk> s (non-varicose, in symptomatic leg) +1 point +1 point Unilateral pitting edema (in symptomatic leg) +1 point — Previous documented<unk>  +1 point — Swelling of entire leg +1 point — Localized tenderness along the<unk>  venous system +1 point — Paralysis, paresis, or recent cast immobilization of lower extremities +1 point — Recently bedridden ≥ 3 days, or major surgery requiring regional or general anesthetic in the past 12 weeks +1 point +1 point Alternative diagnosis at least as likely −2 points — Positive D-dimer (≥ 0.5 mcg/mL or 1.7 nmol/L) — +6 points Absence of leg trauma — +1 point Male sex — +1 point Use of oral contraceptives — +1 point Compression ultrasonography for suspected<unk>  is the standard diagnostic method, and it is highly sensitive for detecting an initial<unk> . A compression ultrasound is considered positive when the<unk>  walls of normally compressible<unk> s 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 the diagnosis. Whole-leg ultrasound is the option that does not require a repeat ultrasound, but proximal compression ultrasound is frequently used because distal<unk>  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<unk> s. CT scan venography, MRI venography, or a non-contrast MRI are also diagnostic possibilities. The gold standard for judging imaging methods is contrast venography, which involves injecting a peripheral<unk>  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.<unk> US.An ultrasound with a blood clot visible in the left common femoral<unk> . (The common femoral<unk>  is distal to the external iliac<unk> .) Ultrasonography of<unk>  of the femoral<unk>  -annotated.Doppler ultrasonography showing absence of flow and hyperechogenic content in a clotted femoral<unk>  (labeled subsartorial) distal to the branching point of the<unk>  femoral<unk> . When compared to this clot, clots that instead obstruct the common femoral<unk>  (proximal to this branching point) cause more severe effects due to impacting a significantly larger portion of the leg. Iliac<unk> <unk> .An abdominal CT scan demonstrating an iliofemoral<unk> , with the clot in the right common iliac<unk>  of the pelvis
Deep vein thrombosis
Hematoma
Varicose veins
Cellulitis
Superficial vein thrombosis
Lymphedema
Venous thrombosis
Baker's cyst