DVT

Deep Venous Thrombosis Author: Kaushal (Kevin) Patel, MD; Chief Editor: Barry E Brenner, MD, PhD, FACEP more...

Updated: Jan 14, 2013

Practice Essentials

Signs and symptoms

Symptoms of deep venous thrombosis (DVT) may include the following:

Edema: Most specific symptomLeg pain: Occurs in 50% of patients but is nonspecificTenderness: Occurs in 75% of patientsWarmth or erythema of the skin over the area of thrombosisClinical symptoms of pulmonary embolism (PE) as the primary manifestation

As many as 46% with patients with classic symptoms have negative venograms,[1] and as many as 50% of those withimage-documented venous thrombosis lack specific symptoms.[1, 2]

No single physical finding or combination of symptoms and signs is sufficiently accurate to establish the diagnosis ofDVT, but physical findings in DVT may include the following:

Calf pain on dorsiflexion of the foot (Homans sign)A palpable, indurated, cordlike, tender subcutaneous venous segmentVariable discoloration of the lower extremityBlanched appearance of the leg because of edema (relatively rare)

Potential complications of DVT include the following:

As many as 40% of patients have silent PE when symptomatic DVT is diagnosed[3]

Paradoxic emboli (rare)Recurrent DVTPostthrombotic syndrome (PTS)

See Clinical Presentation for more detail.

Diagnosis

The American Academy of Family Physicians (AAFP)/American College of Physicians (ACP) recommendations forworkup of patients with probable DVT are as follows:[4]

Validated clinical prediction rules (eg, Wells) should be used to estimate the pretest probability of venousthromboembolism (VTE) and interpret test resultsIn appropriately selected patients with low pretest probability of DVT or PE, it is reasonable to obtain ahigh-sensitivity D-dimerIn patients with intermediate to high pretest probability of lower-extremity DVT, ultrasonography is

Medscape ReferenceReference

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recommendedIn patients with intermediate or high pretest probability of PE, diagnostic imaging studies (eg, ventilation-perfusion scan, multidetector helical CT, and pulmonary angiography) are required

The main laboratory studies to be considered include the following:

D-dimer testingCoagulation studies (eg, prothrombin time and activated partial thromboplastin time to evaluate for ahypercoagulable state

See Workup for more detail.

Management

Treatment options for DVT include the following:

Anticoagulation (mainstay of therapy): Heparins, warfarin, factor Xa inhibitors, and various emerginganticoagulantsPharmacologic thrombolysisEndovascular and surgical interventionsPhysical measures (eg, elastic compression stockings and ambulation)

Heparin products used in the treatment of DVT include the following:

Low-molecular-weight heparin (LMWH; eg, enoxaparin)Unfractionated heparin (UFH)

Factor Xa inhibitors used in the treatment of DVT include the following:

Fondaparinux – The Matisse study found this agent to be comparable to enoxaparin with respect to efficacyand safety[5]

Rivaroxaban – Rivaroxaban was approved by the US Food and Drug Administration (FDA) for thetreatment of DVT or PE and for reduction of the risk of recurrent DVT and PE after initial treatment;data from a pooled analysis of the EINSTEIN-DVT [6] and EINSTEIN-PE [7] trials suggest thatrivaroxaban is as effective in preventing VTE recurrence as enoxaparin followed by a vitamin-Kantagonist and may be associated with less bleeding [8] ; in addition, the data suggest that there areno grounds for avoiding rivaroxaban use in high-risk groups (eg, fragile patients, cancer patients,and patients with a large clot)

Endovascular therapy is performed to reduce the severity and duration of lower-extremity symptoms, prevent PE,diminish the risk of recurrent VTE, and prevent PTS. Percutaneous transcatheter treatment of DVT includes thefollowing:

Thrombus removal with catheter-directed thrombolysis – American College of Chest Physicians (ACCP)recommends thrombolytic therapy only for patients with massive iliofemoral vein thrombosis associated withlimb ischemia or vascular compromiseMechanical thrombectomyAngioplastyStenting of venous obstructions

American Heart Association (AHA) recommendations for inferior vena cava filters include the following[9] :

Confirmed acute proximal DVT or acute PE in patients contraindicated for anticoagulationRecurrent thromboembolism while on anticoagulationActive bleeding complications requiring termination of anticoagulation therapy

See Treatment and Medication for more detail.

Image library


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CT venography showing bilateral deep venous thrombosis. Arrows indicate bilateral deep venous thrombosis.

BackgroundDeep venous thrombosis (DVT) and pulmonary embolism (PE) are manifestations of a single disease entity, namely,venous thromboembolism (VTE). The earliest known reference to peripheral venous disease is found on the Eberpapyrus, which dates from 1550 BC and documents the potentially fatal hemorrhage that may ensue from surgery onvaricose veins. In 1644, Schenk first observed venous thrombosis when he described an occlusion in the inferior venacava. In 1846, Virchow recognized the association between venous thrombosis in the legs and PE.

DVT is the presence of coagulated blood, a thrombus, in one of the deep venous conduits that return blood to theheart. The clinical conundrum is that symptoms (pain and swelling) are often nonspecific or absent. However, if leftuntreated, the thrombus may become fragmented or dislodged and migrate to obstruct the arterial supply to the lung,causing potentially life-threatening PE (See Pathophysiology). See the images below.

Venous thrombus.

Pulmonary embolus.

DVT most commonly involves the deep veins of the leg or arm, often resulting in potentially life-threatening emboli tothe lungs or debilitating valvular dysfunction and chronic leg swelling. Over the past 25 years, the pathophysiology ofDVT has become much better understood, and considerable progress has been made in its diagnosis and treatment.(See Pathophysiology.)

DVT is one of the most prevalent medical problems today, with an annual incidence of 80 cases per 100,000. Eachyear in the United States, more than 200,000 people develop venous thrombosis; of those, 50,000 cases arecomplicated by PE.[10] Lower-extremity DVT is the most common venous thrombosis, with a prevalence of 1 case per1000 population. In addition, it is the underlying source of 90% of acute PEs, which cause 25,000 deaths per year inthe United States (National Center for Health Statistics [NCHS], 2006). (See Epidemiology.)

Conclusive diagnosis has historically required invasive and expensive venography, which is still considered thecriterion standard. The diagnosis may also be obtained noninvasively by means of ultrasonographic examination. (SeeWorkup.)

Early recognition and appropriate treatment of DVT and its complications can save many lives. (See Treatment andManagement.) The goals of pharmacotherapy for DVT are to reduce morbidity, prevent postthrombotic syndrome(PTS), and prevent PE. The primary agents include anticoagulants and thrombolytics. (See Medication.)

Other than the immediate threat of PE, the risk of long-term major disability from postthrombotic syndrome is high.[11,

12, 13, 14, 15]

AnatomyThe peripheral venous system functions both as a reservoir to hold extra blood and as a conduit to return blood fromthe periphery to the heart and lungs. Unlike arteries, which possess 3 well-defined layers (a thin intima, awell-developed muscular media, and a fibrous adventitia), most veins are composed of a single tissue layer. Only thelargest veins possess internal elastic membranes, and this layer is thin and unevenly distributed, providing littlebuttress against high internal pressures. The correct functioning of the venous system depends on a complex seriesof valves and pumps that are individually frail and prone to malfunction, yet the system as a whole performs remarkably


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well under extremely adverse conditions.

Primary collecting veins of the lower extremity are passive, thin-walled reservoirs that are tremendously distensible.Most are suprafascial, surrounded by loosely bound alveolar and fatty tissue that is easily displaced. Thesesuprafascial collecting veins can dilate to accommodate large volumes of blood with little increase in back pressure sothat the volume of blood sequestered within the venous system at any moment can vary by a factor of 2 or morewithout interfering with the normal function of the veins. Suprafascial collecting veins belong to the superficial venoussystem.

Outflow from collecting veins is via secondary conduit veins that have thicker walls and are less distensible. Most ofthese veins are subfascial and are surrounded by tissues that are dense and tightly bound. These subfascial veinsbelong to the deep venous system, through which all venous blood must eventually pass through on its way back to theright atrium of the heart. The lower limb deep venous system is typically thought of as 2 separate systems, one belowthe knee and one above.

The calf has 3 groups of paired deep veins: the anterior tibial veins, draining the dorsum of the foot; the posterior tibialveins, draining the sole of the foot; and the peroneal veins, draining the lateral aspect of the foot. Venous sinusoidswithin the calf muscle coalesce to form soleal and gastrocnemius intramuscular venous plexuses, which join theperoneal veins in the mid calf. These veins play an important role in the muscle pump function of the calf. Just belowthe knee, these tibial veins join to become the popliteal vein, which too can be paired on occasion.

Together, the calf’s muscles and deep vein system form a complex array of valves and pumps, often referred to as the“peripheral heart,” that functions to push blood upward from the feet against gravity. The calf-muscle pump isanalogous to the common hand-pump bulb of a sphygmomanometer filling a blood pressure cuff. Before pumping hasstarted, the pressure is neutral and equal everywhere throughout the system and the calf fills with blood, typically100-150 mL. When the calf contracts, the feeding perforator vein valves are forced closed and the outflow valves areforced open driving the blood proximally. When the calf is allowed to relax, the veins and sinusoids refill from thesuperficial venous system via perforating veins, and the outflow valve is then forced shut, preventing retrograde flow.With each “contraction,” 40-60% of the calf’s venous volume is driven proximally.[16]

The deep veins of the thigh begin distally with the popliteal vein as it courses proximally behind the knee and thenpasses through the adductor canal, at which point its name changes to the femoral vein. (This important deep vein issometimes incorrectly referred to as the superficial femoral vein in a misguided attempt to distinguish it from theprofunda femoris, or deep femoral vein, a short, stubby vein that usually has its origin in terminal muscle tributarieswithin the deep muscles of the lateral thigh but may communicate with the popliteal vein in up to 10% of patients.

The term superficial femoral vein should never be used, because the femoral vein is in fact a deep vein and is not partof the superficial venous system. This incorrect term does not appear in any definitive anatomic atlas, yet it has comeinto common use in vascular laboratory practice. Confusion arising from use of the inappropriate name has beenresponsible for many cases of clinical mismanagement and death.) In theproximal thigh,the femoral vein and the deepfemoral vein unite to form the common femoral vein, which passes upwards above the groin crease to become theiliac vein.

The external iliac vein is the continuation of the femoral vein as it passes upward behind the inguinal ligament. At thelevel of the sacroiliac joint, it unites with the hypogastric vein to form the common iliac vein. The left common iliac islonger than the right and more oblique in its course, passing behind the right common iliac artery. This anatomicasymmetry sometimes results in compression of the left common iliac vein by the right common iliac artery to produceMay-Thurner syndrome, a left-sided iliac outflow obstruction with localized adventitial fibrosis and intimal proliferation,often with associated deep venous thrombosis. At the level of the fifth lumbar vertebra, the 2 common iliac veins cometogether at an acute angle to form the inferior vena cava.

Please go to the main article on Inferior Vena Caval Thrombosis for more information.

PathophysiologyOver a century ago, Rudolf Virchow described 3 factors that are critically important in the development of venousthrombosis: (1) venous stasis, (2) activation of blood coagulation, and (3) vein damage. These factors have come tobe known as the Virchow triad.

Venous stasis can occur as a result of anything that slows or obstructs the flow of venous blood. This results in anincrease in viscosity and the formation of microthrombi, which are not washed away by fluid movement; the thrombusthat forms may then grow and propagate. Endothelial (intimal) damage in the blood vessel may be intrinsic orsecondary to external trauma. It may result from accidental injury or surgical insult. A hypercoagulable state can occurdue to a biochemical imbalance between circulating factors. This may result from an increase in circulating tissueactivation factor, combined with a decrease in circulating plasma antithrombin and fibrinolysins.

Over time, refinements have been made in the description of these factors and their relative importance to thedevelopment of venous thrombosis. The origin of venous thrombosis is frequently multifactorial, with components of


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the Virchow triad assuming variable importance in individual patients, but the end result is early thrombus interactionwith the endothelium. This interaction stimulates local cytokine production and facilitates leukocyte adhesion to theendothelium, both of which promote venous thrombosis. Depending on the relative balance between activatedcoagulation and thrombolysis, thrombus propagation occurs.

Decreased vein wall contractility and vein valve dysfunction contribute to the development of chronic venousinsufficiency. The rise in ambulatory venous pressure causes a variety of clinical symptoms of varicose veins, lowerextremity edema, and venous ulceration.

Development of thrombosis

Thrombosis is the homeostatic mechanism whereby blood coagulates or clots, a process crucial to the establishmentof hemostasis after a wound. It may be initiated via several pathways, usually consisting of cascading activation ofenzymes that magnify the effect of an initial trigger event. A similar complex of events results in fibrinolysis, or thedissolution of thrombi. The balance of trigger factors and enzymes is complex. Microscopic thrombus formation andthrombolysis (dissolution) are continuous events, but with increased stasis, procoagulant factors, or endothelial injury,the coagulation-fibrinolysis balance may favor the pathologic formation of an obstructive thrombus. Clinically relevantdeep venous thrombosis is the persistent formation of macroscopic thrombus in the deep proximal veins.

For the most part, the coagulation mechanism consists of a series of self-regulating steps that result in the productionof a fibrin clot. These steps are controlled by a number of relatively inactive cofactors or zymogens, which, whenactivated, promote or accelerate the clotting process. These reactions usually occur at the phospholipid surface ofplatelets, endothelial cells, or macrophages. Generally, the initiation of the coagulation process can be divided into 2distinct pathways, an intrinsic system and an extrinsic system (see the image below).

Coagulation pathway.

The extrinsic system operates as the result of activation by tissue lipoprotein, usually released as the result of somemechanical injury or trauma. The intrinsic system usually involves circulating plasma factors. Both of these pathwayscome together at the level of factor X, which is activated to form factor Xa. This in turn promotes the conversion ofprothrombin to thrombin (factor II). This is the key step in clot formation, for active thrombin is necessary for thetransformation of fibrinogen to a fibrin clot.

Once a fibrin clot is formed and has performed its function of hemostasis, mechanisms exist in the body to restore thenormal blood flow by lysing the fibrin deposit. Circulating fibrinolysins perform this function. Plasmin digests fibrin andalso inactivates clotting factors V and VIII and fibrinogen.

Three naturally occurring anticoagulant mechanisms exist to prevent inadvertent activation of the clotting process.These include the heparin-antithrombin III (ATIII), protein C and thrombomodulin protein S, and the tissue factorinhibition pathways. When trauma occurs, or when surgery is performed, circulating ATIII is decreased. This has theeffect of potentiating the coagulation process. Studies have demonstrated that levels of circulating ATIII is decreasedmore, and stay reduced longer, after total hip replacement (THR) than after general surgical cases (see the imagebelow).

Postoperative antithrombin III levels.

Furthermore, patients who have positive venograms postoperatively tend to be those in whom circulating levels ofATIII are diminished (see the image below).


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Antithrombin III levels and deep venous thrombosis formation.

Under normal circumstances, a physiologic balance is present between factors that promote and retard coagulation. Adisturbance in this equilibrium may result in the coagulation process occurring at an inopportune time or location or inan excessive manor. Alternatively, failure of the normal coagulation mechanisms may lead to hemorrhage.

Thrombus usually forms behind valve cusps or at venous branch points, most of which begin in the calf. Venodilationmay disrupt the endothelial cell barrier and expose the subendothelium. Platelets adhere to the subendothelial surfaceby means of von Willebrand factor or fibrinogen in the vessel wall. Neutrophils and platelets are activated, releasingprocoagulant and inflammatory mediators. Neutrophils also adhere to the basement membrane and migrate into thesubendothelium. Complexes form of the surface of platelets and increase the rate of thrombin generation and fibrinformation. Stimulated leukocytes irreversibly bind to endothelial receptors and extravasate into the vein wall by meansof mural chemotaxis. Because mature thrombus composed of platelets, leukocytes and fibrin develops, and an activethrombotic and inflammatory process occurs at the inner surface of the vein, and an active inflammatory responseoccurs in the wall of the vein.[17, 18]

Studies have shown that low flow sites, such as the soleal sinuses, behind venous valve pockets, and at venousconfluences, are at most risk for the development of venous thrombi.[19, 20] However, stasis alone is not enough tofacilitate the development of venous thrombosis. Experimental ligation of rabbit jugular veins for periods of up to 60minutes have failed to consistently cause venous thrombosis.[21, 22] Although, patients that are immobilized for longperiods of time seem to be at high risk for the development of venous thrombosis, an additional stimulus is required todevelop DVT.

Evolution of venous insufficiency

Over time, thrombus organization begins with the infiltration of inflammatory cells into the clot. This results in afibroelastic intimal thickening at the site of thrombus attachment in most patients and a fibrous synechiae in up to11%.[23] In many patients, this interaction between vessel wall and thrombus leads to valvular dysfunction and overallvein wall fibrosis. Histological examination of vein wall remodeling after venous thrombosis has demonstrated animbalance in connective tissue matrix regulation and a loss of regulatory venous contractility that contributes to thedevelopment of chronic venous insufficiency.[24, 25] Some form of chronic venous insufficiency develops in 29-79% ofpatients with an acute DVT, while ulceration is noted in 4-6%.[26, 27] The risk has been reported to be 6 times greater inthose patients with recurrent thrombosis.[28]

Over a few months, most acute DVTs evolve to complete or partial recanalization, and collaterals develop (see theimages below).[29, 30, 31, 32, 33, 34] Although blood flow may be restored, residual evidence of thrombus or stenosis isobserved in half the patients after 1 year. Furthermore, the damage to the underlying valves and those compromisedby peripheral dilation and insufficiency usually persists and may progress. Venous stasis, venous reflux, and chronicedema are common in patients who have had a large DVT.[35]

Lower-extremity venogram shows outlining of an acute deep venous thrombosis in the popliteal vein with contrast enhancement.


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Lower-extremity venogram shows a nonocclusive chronic thrombus. The superficial femoral vein (lateral vein) has the appearance of 2parallel veins, when in fact, it is 1 lumen containing a chronic linear thrombus. Although the chronic clot is not obstructive after itrecanalizes, it effectively causes the venous valves to adhere in an open position, predisposing the patient to reflux in the involvedsegment.

The acute effect of an occluded outflow vein may be minimal if adequate collateral pathways exist. As an alternative, itmay produce marked pain and swelling if flow is forced retrograde. In the presence of deep vein outflow obstruction,contraction of the calf muscle produces dilation of the feeding perforating veins, it renders the valves nonfunctional(because the leaflets no longer coapt), and it forces the blood retrograde through the perforator branches and into thesuperficial system. This high-pressure flow may cause dilation of the superficial (usually low-pressure) system andproduce superficial venous incompetence. In clinical terms, the increased incidence of reflux in the ipsilateral greatersaphenous vein increases 8.7-fold on follow-up of DVT.[29] This chain of events (ie, obstruction to antegrade flowproducing dilation, stasis, further valve dysfunction, with upstream increased pressure, dilation, and other processes)may produce hemodynamic findings of venous insufficiency.

Another mechanism that contributes to venous incompetence is the natural healing process of the thrombotic vein.The thrombotic mass is broken down over weeks to months by inflammatory reaction and fibrinolysis, and the valvesand venous wall are altered by organization and ingrowth of smooth muscle cells and production of neointima. Thisprocess leaves damaged, incompetent, underlying valves, predisposing them to venous reflux. The muralinflammatory reaction breaks down collagen and elastin, leaving a noncompliant venous wall.[29, 30, 31, 32, 33, 34]

Persistent obstructive thrombus, coupled with valvular damage, ensures continuation of this cycle. Over time, thevenous damage may become irreversible. Hemodynamic venous insufficiency is the underlying pathology ofpostthrombotic syndrome (PTS), also referred to as postphlebitic syndrome. If numerous valves are affected, flowdoes not occur centrally unless the leg is elevated. Inadequate expulsion of venous blood results in stasis and apersistently elevated venous pressure or venous hypertension. As fibrin extravasates and inflammation occurs, thesuperficial tissues become edematous and hyperpigmented. With progression, fibrosis compromises tissueoxygenation, and ulceration may result. After venous insufficiency occurs, no treatment is ideal; elevation and use ofcompression stockings may compensate, or surgical thrombectomy or venous bypass may be attempted.[36, 37, 38, 39]

With anticoagulation alone, as many as 75% of patients with symptomatic DVT present with PTS at 5-10 years.[39, 40]

However, the incidence of venous ulceration is far less, at 5%. Of the half million patients with venous ulcers in theUnited States, 17-45% report having a history of DVT.[41]

Lower-extremity deep venous thrombosis

Most small thrombi in the lower extremities tend to resolve spontaneously after surgery. In about 15% of cases,however, these thrombi may extend into the proximal femoral venous system of the leg. Untreated proximal thrombirepresent a significant source of clinically significant pulmonary emboli.

In the absence of rhythmic contraction of the leg muscles, as in walking or moving, blood flow in the veins slows andeven stops in some areas, predisposing patients to thrombosis.[42]

In the postoperative patient, as many as one half of all isolated calf vein thrombi resolve spontaneously within a fewhours, whereas approximately 15% extend to involve the femoral vein. A many as one third of untreated symptomaticcalf vein DVT extend to the proximal veins.[43] At 1-month follow-up of untreated proximal DVT, 20% regress and 25%propagate. Although calf vein thrombi are rare sources of clinically significant PE, the incidence of PE with untreatedproximal thrombi is 29-50%.[44, 43] Most PEs are first diagnosed at autopsy.[45, 46]

Upper-extremity deep venous thrombosis

The 2 forms of upper-extremity DVT are (1) effort-induced thrombosis (Paget-von Schrötter syndrome) and (2)secondary thrombosis.

Effort induced thrombosis, or Paget-von Schrötter syndrome, accounts for 25% of cases.[47] Paget in England and vonSchrötter in Germany independently described effort thrombosis more than 100 years ago. In this primary form of thedisease, an underlying chronic venous compressive abnormality caused by the musculoskeletal structures in the


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costoclavicular space is present at the thoracic inlet and/or outlet. See the images below.

This contrast-enhanced study was obtained through a Mediport placed through the chest wall through the internal jugular vein to facilitatechemotherapy. A thrombus has propagated peripherally from the tip of the catheter in the superior vena cava into both subclavian veins.

Superior vena cava syndrome in a patient with lung cancer. CT scan demonstrates a hypoattenuating thrombus that fills the superiorvena cava. The patient was treated with anticoagulation alone.

In 75% of patients with secondary thrombosis, hypercoagulability and/or indwelling central venous catheters areimportant contributing factors. In fact, with the advent of central venous catheters, upper-extremity and brachiocephalicvenous thrombosis has become a more common problem.[48, 49, 50, 51]

For more information on upper-extremity DVT, see Imaging in Deep Venous Thrombosis of the Upper Extremity.

Pulmonary embolism

PE develops as venous thrombi break off from their location of origin and travel through the right heart and into thepulmonary artery, causing a ventilation perfusion defect and cardiac strain. PE occurs in approximately 10% of patientswith acute DVT and can cause up to 10% of in hospital deaths.[52, 53] However, most patients (up to 75%) areasymptomatic. Traditionally, proximal venous thrombosis are thought to be at highest risk for causing pulmonaryemboli; however, the single largest autopsy series ever performed to specifically to look for the source of fatal PE wasperformed by Havig in 1977, who found that one third of the fatal emboli arose directly from the calf veins.[54]

EtiologyNumerous factors, often in combination, contribute to DVT. These may be categorized as acquired (eg, medication,illness) or congenital (eg, anatomic variant, enzyme deficiency, mutation). A useful categorization may be an acuteprovoking condition versus a chronic condition, as this distinction affects the length of anticoagulant therapy.

The frequent causes of DVT are due to augmentation of venous stasis due to immobilization or central venousobstruction. Immobility can be as transient as that occurring during a transcontinental airplane flight or that during anoperation under general anesthesia. It can also be extended, as during hospitalization for pelvic, hip, or spinal surgery,or due to stroke or paraplegia. Individuals in these circumstances warrant surveillance, prophylaxis, and treatment ifthey develop DVT.[55, 56]

Reduced blood flow from increased blood viscosity or central venous pressure

Increased blood viscosity may decrease venous blood flow. This change may be due to an increase in the cellularcomponent of the blood in polycythemia rubra vera or thrombocytosis or a decrease in the fluid component due todehydration.


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Increased central venous pressure, either mechanical or functional, may reduce the flow in the veins of the leg. Masseffect on the iliac veins or inferior vena cava from neoplasm, pregnancy, stenosis, or congenital anomaly increasesoutflow resistance.

Anatomic variants contributing to venous stasis

Anatomic variants that result in diminution or absence of the inferior vena cava or iliac veins may contribute to venousstasis. In iliocaval thromboses, an underlying anatomic contributor is identified in 60-80% of patients. The best-knownanomaly is compression of left common iliac vein at the anatomic crossing of the right common iliac artery. The veinnormally passes under the right common iliac artery during its normal course.

In some individuals, this anatomy results in compression of the left iliac vein and can lead to band or web formation,subsequent stasis, and left leg DVT. The reasons are poorly understood. Compression of the iliac vein is also calledMay-Thurner syndrome or Cockett syndrome.

Inferior vena cava variants are uncommon. Anomalous development is most commonly detected and diagnosed oncross-sectional imaging or venography. The embryologic evolution of the inferior vena cava is from an enlargement oratrophy of paired supracardinal and subcardinal veins. Anomalous embryologic development may result in absence ofthe normal cava. These variations may increase the risk of symptoms because small-caliber vessels may be mostsubject to obstruction. In patients younger than 50 years who have deep venous thrombosis, the incidence of a cavalanomaly is as high as 5%.[57]

A double or duplicated inferior vena cava results from lack of atrophy in part of the left supracardinal vein, resulting in aduplicate structure to the left of the aorta. The common form is a partial paired inferior vena cava that connects the leftcommon iliac and left renal veins. When caval interruption, such as placement of a filter, is planned, these alternatepathways must be considered. As an alternative, the inferior vena cava may not develop. The most common alternateroute for blood flow is through the azygous vein, which enlarges to compensate. If a venous stenosis is present at thecommunication of iliac veins and azygous vein, back pressure can result in insufficiency, stasis, or thrombosis.[58]

In rare cases, neither the inferior vena cava nor the azygous vein develops, and the iliac veins drain through internaliliac collaterals to the hemorrhoidal veins and superior mesenteric vein to the portal system of the liver. Hepatic venousdrainage to the atrium is patent. Because this pathway involves small hemorrhoidal vessels, thrombosis of these veinscan cause severe acute swelling of the legs.

Thrombosis of the inferior vena cava is a rare occurrence and is an unusual result of leg deep venous thrombosisunless an inferior vena cava filter is present and stops a large embolus in the cava, resulting in obstruction andextension of thrombosis. Common causes of caval thrombosis include tumors involving the kidney or liver, tumorsinvading the inferior vena cava, compression of the inferior vena cava by extrinsic mass, and retroperitonealfibrosis.[59, 60]

Mechanical injury to vein

Mechanical injury to the vein wall appears to provide an added stimulus for venous thrombosis. Hip arthroplastypatients with the associated femoral vein manipulation represent a high-risk group that cannot be explained by justimmobilization, with 57% of thrombi originating in the affected femoral vein rather than the usual site of stasis in thecalf.[61] Endothelial injury can convert the normally antithrombogenic endothelium to become prothrombotic bystimulating the production of tissue factor, von Willebrand factor, and fibronectin.

Injury may be obvious, such as those due to trauma, surgical intervention, or iatrogenic injury, but they may also beobscure, such as those due to remote deep venous thrombosis (perhaps asymptomatic) or minor (forgotten) trauma.Previous DVT is a major risk factor for further DVT. The increased incidence of DVT in the setting of acute urinary tractor respiratory infection may be due to an inflammation-induced alteration in endothelial function.

Common risk factors for deep venous thrombosis

The presence of risk factors plays a prominent role in the assessing the pretest probability of DVT. Furthermore,transient risk factors permit successful short-term anticoagulation, whereas idiopathic deep venous thrombosis orchronic or persistent risk factors warrant long-term therapy.

In the MEDENOX study that evaluated 1102 acutely ill, immobilized admitted general medical patients, multiple logisticregression analysis found the following factors to be significantly and independently associated with an increased riskfor VTE, most of which were asymptomatic and diagnosed by venography of both lower extremities[62] :

Presence of an acute infectious diseaseAge older than 75 yearsCancerHistory of prior VTE


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The most common risk factors are obesity, previous VTE, malignancy, surgery, and immobility. Each is found in20-30% of patients. Hospitalized and nursing home patients often have several risk factors and account for one half ofall DVT (with an incidence of 1 case per 100 population).[45, 63]

The single most powerful risk marker remains a prior history of DVT with as many as 25% of acute venous thrombosisoccurring in such patients.[64] Pathologically, remnants of previous thrombi are often seen within the specimens of newacute thrombi. However, recurrent thrombosis may actually be the result of primary hypercoagulable states.Abnormalities within the coagulation cascade are the direct result of discrete genetic mutations within the coagulationcascade. Deficiencies of protein C, protein S, or antithrombin III account for approximately 5-10% of all cases ofDVT.[65]

Age has been well studied as an independent risk factor for venous thrombosis development. Although a 30-foldincrease in incidence is noted from age 30 to age 80, the effect appears to be multifactorial, with more thrombogenicrisk factors occurring in the elderly than in those younger than 40 years.[64, 66] Venous stasis, as seen in immobilizedpatients and paralyzed limbs, also contributes to the development of venous thrombosis. Autopsy studies parallel theduration of bed rest to the incidence of venous thrombosis, with 15% of patients in those studies dying within 7 days ofbedrest to greater than 80% in those dying after 12 weeks.[19] Within stroke patients, DVT is found in 53% of paralyzedlimbs, compared with only 7% on the nonaffected side.[67]

Malignancy is noted in as many as 30% of patients with venous thrombosis.[64, 68] The thrombogenic mechanismsinvolve abnormal coagulation, as evidenced by 90% of cancer patients having some abnormal coagulation factors.[69]

Chemotherapy may increase the risk of venous thrombosis by affecting the vascular endothelium, coagulationcascades, and tumor cell lysis. The incidence has been shown to increase in those patients undergoing longercourses of therapy for breast cancer, from 4.9% for 12 weeks of treatment to 8.8% for 36 weeks.[70] Additionally, DVTcomplicates 29% of surgical procedures done for malignancy.[71]

Postoperative venous thrombosis varies depending on a multitude of patient factors, including the type of surgeryundertaken. Without prophylaxis, general surgery operations typically have an incidence of DVT around 20%, whereasorthopedic hip surgery can occur in up to 50% of patients.[72] The nature of orthopedic illnesses and diseases, trauma,and surgical repair or replacement of hip and knee joints predisposes patients to the occurrence of VTE disease.These complications are predictable and are the result of alterations of the natural equilibrium mechanisms in variousdisease states.[73] For more information, see Deep Venous Thrombosis Prophylaxis.

Based on radioactive labeled fibrinogen, about half of lower extremity thrombi develop intraoperatively.[74]

Perioperative immobilization, coagulation abnormalities, and venous injury all contribute to the development of surgicalvenous thrombosis.

Genetic factors

Genetic mutations within the blood’s coagulation cascade represent those at highest risk for the development ofvenous thrombosis. Genetic thrombophilia is identified in 30% of patients with idiopathic venous thrombosis. Primarydeficiencies of coagulation inhibitors antithrombin, protein C, and protein S are associated with 5-10% of all thromboticevents.[75, 76, 77] Altered procoagulant enzyme proteins include factor V, factor VIII, factor IX, factor XI, andprothrombin. Resistance of procoagulant factors to an intact anticoagulation system has also recently been describedwith the recognition of factor V Leiden mutation, representing 10-65% of patients with DVT.[78] In the setting of venousstasis, these factors are allowed to accumulate in thrombosis prone sites, where mechanical vessel injury hasoccurred, stimulating the endothelium to become prothrombotic.[79]

Factor V Leiden is a mutation that results in a form of factor Va that resists degradation by activated protein C, leadingto a hypercoagulable state. Its importance lies in the 5% prevalence in the American population and its association witha 3-fold to 6-fold increased risk for VTE. Antiphospholipid syndrome is considered a disorder of the immune system,where antiphospholipid antibodies (cardiolipin or lupus anticoagulant antibodies) are associated with a syndrome ofhypercoagulability. Although not a normal blood component, the antiphospholipid antibody may be asymptomatic. It ispresent in 2% of the population, and it may be detected in association with infections or the administration of certaindrugs, including antibiotics, cocaine, hydralazine, procainamide, and quinine.[76]

Tests for these genetic defects are often not performed in patients with recurrent venous thrombosis because therapyremains symptomatic. In most patients with these genetic defects, lifetime anticoagulation therapy with warfarin or lowmolecular weight heparin (LMWH) is recommended after recurrent DVT without an alternative identifiable etiologydocumented. The risk of recurrent DVT is multiplied 1.4-2 times, with the most common genetic polymorphismspredisposing individuals to DVT. However, the low incidence of factor V Leiden and prothrombin G20210A may notwarrant aggressive prophylaxis. Therefore, genetic testing might not be warranted until a second event occurs.[80]

Other conditions that can induce hypercoagulability


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Other diseases and states can induce hypercoagulability in patients without other underlying risks for DVT. They canpredispose patients to DVT, though their ability to cause DVT without intrinsic hypercoagulability is in question. Theconditions include malignancy, dehydration, and use of medications (eg, estrogens). Acute hypercoagulable statesalso occur, as in disseminated intravascular coagulopathy (DIC) resulting from infection or heparin-inducedthrombocytopenia.[81]

Summary of risk factors

A summary of risk factors is as follows:

AgeImmobilization longer than 3 daysPregnancy and the postpartum periodMajor surgery in previous 4 weeksLong plane or car trips (>4 h) in previous 4 weeksCancerPrevious DVTStrokeAcute myocardial infarction (AMI)Congestive heart failure (CHF)SepsisNephrotic syndromeUlcerative colitisMultiple traumaCNS/spinal cord injuryBurnsLower extremity fracturesSystemic lupus erythematosus (SLE) and the lupus anticoagulantBehçet syndromeHomocystinuriaPolycythemia rubra veraThrombocytosisInherited disorders of coagulation/fibrinolysisAntithrombin III deficiencyProtein C deficiencyProtein S deficiencyProthrombin 20210A mutationFactor V LeidenDysfibrinogenemias and disorders of plasminogen activationIntravenous (IV) drug abuseOral contraceptivesEstrogensHeparin-induced thrombocytopenia (HIT)

EpidemiologyDVT and thromboembolism remain a common cause of morbidity and mortality in bedridden or hospitalized patients,as well as generally healthy individuals. The exact incidence of DVT is unknown because most studies are limited bythe inherent inaccuracy of clinical diagnosis. Existing data that probably underestimate the true incidence of DVTsuggest that about 80 cases per 100,000 population occur annually. Approximately 1 person in 20 develops a DVT inthe course of his or her lifetime. About 600,000 hospitalizations per year occur for DVT in the United States.

In elderly persons, the incidence is increased 4-fold. The in-hospital case-fatality rate for VTE is 12%, rising to 21% inelderly persons. In hospitalized patients, the incidence of venous thrombosis is considerably higher and varies from20-70%. Venous ulceration and venous insufficiency of the lower leg, which are long-term complications of DVT, affect0.5% of the entire population. Extrapolation of these data reveals that as many as 5 million people have venous stasisand varying degrees of venous insufficiency.

Age distribution for deep venous thrombosis

Deep venous thrombosis usually affects individuals older than 40 years. The incidence of VTE increases with age inboth sexes. The age-standardized incidence of first-time VTE is 1.92 per 1000 person-years.

Prevalence of deep venous thrombosis by sex

The male-to-female ratio is 1.2:1, indicating that males have a higher risk of DVT than females.


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Prevalence of deep venous thrombosis by race

From a demographic viewpoint, Asian and Hispanic populations have a lower risk of VTE, whereas whites and blackshave a higher risk (2.5-4 times higher).

PrognosisMost DVT is occult and usually resolves spontaneously without complication. The principal long-term morbidity fromDVT is PTS, which complicates about a quarter of cases of symptomatic proximal DVT; most cases develop within 2years afterward.

Death from DVT is attributed to massive PE, which causes as many as 300,000 deaths annually in the UnitedStates.[82] PE is the leading cause of preventable in-hospital mortality. The Longitudinal Investigation ofThromboembolism Etiology (LITE) that combined data from two prospective cohort studies, the Atherosclerosis Riskin Communities (ARIC) and the Cardiovascular Health Study (CHS) determined the incidence of symptomatic DVTand pulmonary embolism in 21,680 participants aged 45 years or older who were followed for 7.6 years.[83]

Patient EducationFor excellent patient education resources, visit eMedicineHealth’s Lung and Airway Center.

Also, see eMedicineHealth’s patient education articles Blood Clot in the Legs, Deep Vein Thrombosis (Blood Clot inthe Leg, DVT), Phlebitis, and Pulmonary Embolism.

Contributor Information and DisclosuresAuthorKaushal (Kevin) Patel, MD Vascular Surgeon, Kaiser Permanente Los Angeles Medical Center

Disclosure: Nothing to disclose.

Coauthor(s)Linda J Chun, MD Resident Physician, Department of Surgery, Los Angeles Medical Center, Kaiser Permanente


Chief EditorBarry E Brenner, MD, PhD, FACEP Professor of Emergency Medicine, Professor of Internal Medicine, ProgramDirector for Emergency Medicine, Case Medical Center, University Hospitals, Case Western Reserve UniversitySchool of Medicine

Barry E Brenner, MD, PhD, FACEP is a member of the following medical societies: Alpha Omega Alpha, AmericanAcademy of Emergency Medicine, American College of Chest Physicians, American College of EmergencyPhysicians, American College of Physicians, American Heart Association, American Thoracic Society, ArkansasMedical Society, New York Academy of Medicine, New York Academy of Sciences, and Society for AcademicEmergency Medicine


Additional ContributorsMarc D Basson, MD, PhD, MBA, FACS Professor, Chair, Department of Surgery, Assistant Dean for FacultyDevelopment in Research, Michigan State University College of Human Medicine

Marc D Basson, MD, PhD, MBA, FACS is a member of the following medical societies: Alpha Omega Alpha,American College of Surgeons, American Gastroenterological Association, Phi Beta Kappa, and Sigma Xi


12 of 27 05/02/2013 6:21


John J Borsa, MD Consulting Staff, Department of Radiology, St Joseph Medical Center

John J Borsa, MD is a member of the following medical societies: American College of Radiology, AmericanSociety of Neuroradiology, Cardiovascular and Interventional Radiological Society of Europe, Radiological Societyof North America, Royal College of Physicians and Surgeons of Canada, and Society of Interventional Radiology


Hearns W Charles, MD Assistant Professor of Radiology, New York University School of Medicine; AttendingPhysician, Division of Vascular and Interventional Radiology, Department of Radiology, New York University MedicalCenter

Hearns W Charles, MD is a member of the following medical societies: American College of Radiology, AmericanRoentgen Ray Society, Radiological Society of North America, and Society of Cardiovascular and InterventionalRadiology


Kyung J Cho, MD, FACR William Martel Professor of Radiology, Interventional Radiology Fellowship Director,University of Michigan Health System

Kyung J Cho, MD, FACR is a member of the following medical societies: American College of Radiology, AmericanHeart Association, American Medical Association, American Roentgen Ray Society, Association of UniversityRadiologists, and Radiological Society of North America


Douglas M Coldwell, MD, PhD Professor of Radiology, Director, Division of Vascular and InterventionalRadiology, University of Louisville School of Medicine

Douglas M Coldwell, MD, PhD is a member of the following medical societies: American Association for CancerResearch, American College of Radiology, American Heart Association, American Physical Society, AmericanRoentgen Ray Society, Society of Cardiovascular and Interventional Radiology, Southwest Oncology Group, andSpecial Operations Medical Association

Disclosure: Sirtex, Inc. Consulting fee Speaking and teaching; DFINE, Inc. Honoraria Consulting

Francis Counselman, MD, FACEP Chair, Professor, Department of Emergency Medicine, Eastern VirginiaMedical School

Francis Counselman, MD, FACEP is a member of the following medical societies: Alpha Omega Alpha, AmericanCollege of Emergency Physicians, Association of Academic Chairs of Emergency Medicine (AACEM), NorfolkAcademy of Medicine, and Society for Academic Emergency Medicine


Paul E Di Cesare, MD, FACS Professor and Chair, Department of Orthopedic Sugery, University of California,Davis, School of Medicine

Paul E Di Cesare, MD, FACS is a member of the following medical societies: American Academy of OrthopaedicSurgeons, American College of Surgeons, and Sigma Xi

Disclosure: Stryker Consulting fee Consulting

Robert S Ennis, MD, FACS Associate Professor, Department of Orthopedic Surgery, University of Miami Schoolof Medicine; President, OrthoMed Consulting Services, Inc

Robert S Ennis, MD, FACS is a member of the following medical societies: American Academy of OrthopaedicSurgeons, American College of Surgeons, and Florida Orthopaedic Society


Craig F Feied, MD, FACEP, FAAEM, FACPh Professor of Emergency Medicine, Georgetown University School ofMedicine; General Manager, Microsoft Enterprise Health Solutions Group


Luis G Fernandez, MD, KHS, FACS, FASAS, FCCP, FCCM, FICS Assistant Clinical Professor of Surgery andFamily Practice, University of Texas Health Science Center; Adjunct Clinical Professor of Medicine and Nursing,University of Texas, Arlington; Chairman, Division of Trauma Surgery and Surgical Critical Care, Chief of Trauma


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Surgical Critical Care Unit, Trinity Mother Francis Health System; Brigadier General, Texas Medical Rangers,TXSG/MB

Luis G Fernandez, MD, KHS, FACS, FASAS, FCCP, FCCM, FICS is a member of the following medical societies:American Association for the Surgery of Trauma, American College of Chest Physicians, American College ofLegal Medicine, American College of Surgeons, American Society of Abdominal Surgeons, American Society ofGeneral Surgeons, American Society of General Surgeons, American Society of Law, Medicine & Ethics, AmericanTrauma Society, Association for SurgicalEducation, Association of Military Surgeons of the US, Chicago MedicalSociety, Illinois State Medical Society, International College of Surgeons, New York Academy of Sciences, PanAmerican Trauma Society, Society of Critical Care Medicine, Society of Laparoendoscopic Surgeons, SoutheasternSurgical Congress, Texas Medical Association, and Undersea and Hyperbaric Medical Society


Douglas M Geehan, MD Associate Professor, Department of Surgery, University of Missouri at Kansas City

Douglas M Geehan, MD is a member of the following medical societies: American College of Surgeons, AmericanInstitute of Ultrasound in Medicine, American Medical Association, Association for Academic Surgery, Phi BetaKappa, Society of American Gastrointestinal and Endoscopic Surgeons, and Society of Critical Care Medicine


John Geibel, MD, DSc, MA Vice Chair and Professor, Department of Surgery, Section of GastrointestinalMedicine, and Department of Cellular and Molecular Physiology, Yale University School of Medicine; Director,Surgical Research, Department of Surgery, Yale-New Haven Hospital

John Geibel, MD, DSc, MA is a member of the following medical societies: American GastroenterologicalAssociation, American Physiological Society, American Society of Nephrology, Association for Academic Surgery,International Society of Nephrology, New York Academy of Sciences, and Society for Surgery of the AlimentaryTract

Disclosure: AMGEN Royalty Consulting; ARdelyx Ownership interest Board membership

Harris Gellman, MD Consulting Surgeon, Broward Hand Center; Voluntary Clinical Professor of OrthopedicSurgery and Plastic Surgery, Departments of Orthopedic Surgery and Surgery, University of Miami, Leonard M MillerSchool of Medicine

Harris Gellman, MD is a member of the following medical societies: American Academy of Medical Acupuncture,American Academy of Orthopaedic Surgeons, American Orthopaedic Association, American Society for Surgery ofthe Hand, and Arkansas Medical Society


Craig Greben, MD Assistant Professor of Radiology, Hofstra University School of Medicine; Chief, Division ofVascular and Interventional Radiology, North Shore University Hospital

Craig Greben, MD is a member of the following medical societies: Society of Cardiovascular and InterventionalRadiology


Lars Grimm, MD, MHS House Staff, Department of Diagnostic Radiology, Duke University Medical Center


Michael A Grosso, MD Consulting Staff, Department of Cardiothoracic Surgery, St Francis Hospital

Michael A Grosso, MD is a member of the following medical societies: American College of Surgeons, Society ofThoracic Surgeons, and Society of University Surgeons


George Hartnell, MBChB Professor of Radiology, Tufts University School of Medicine; Director of Cardiovascularand Interventional Radiology, Department of Radiology, Baystate Medical Center

George Hartnell, MBChB is a member of the following medical societies: American College of Cardiology,American College of Radiology, American Heart Association, Association of University Radiologists, British Instituteof Radiology, British Medical Association, Massachusetts Medical Society, Radiological Society of North America,Royal College of Physicians, Royal College of Radiologists, andSociety of Cardiovascular and InterventionalRadiology


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Eric K Hoffer, MD Director, Vascular and Interventional Radiology, Associate Professor of Radiology, Section ofAngiography and Interventional Radiology, Dartmouth-Hitchcock Medical Center

Eric K Hoffer, MD is a member of the following medical societies: American Heart Association, Radiological Societyof North America, Society for Cardiac Angiography and Interventions, and Society of Interventional Radiology


James Quan-Yu Hwang, MD, RDMS, RDCS, FACEP Staff Physician, Emergency Department, KaiserPermanente

James Quan-Yu Hwang, MD, RDMS, RDCS, FACEP is a member of the following medical societies: AmericanAcademy of Emergency Medicine, American College of Emergency Physicians, American Institute of Ultrasound inMedicine, and Society for Academic Emergency Medicine

Disclosure: 3rd Rock Ultrasound, LLC Salary Speaking and teaching; Schlesinger Associates Consulting feeConsulting; Philips Ultrasound Consulting fee Consulting

Bartholomew Kwan, MBBS, FRCPC, FRCR Staff Radiologist, Department of Medical Imaging, WOHC BramptonCivic Hospital

Bartholomew Kwan, MBBS, FRCPC, FRCR is a member of the following medical societies: American RoentgenRay Society, Cardiovascular and Interventional Radiological Society of Europe, Radiological Society of NorthAmerica, Royal College of Physicians and Surgeons of Canada, Royal College of Radiologists, and Society ofInterventional Radiology


William C Manson, MD Director of Emergency Ultrasound, Department of Emergency Medicine, Emory UniversitySchool of Medicine

William C Manson, MD is a member of the following medical societies: American College of EmergencyPhysicians, American Institute of Ultrasound in Medicine, Emergency Medicine Residents Association, and Societyfor Academic Emergency Medicine

Disclosure: The Emergency Ultrasound Course Honoraria Speaking and teaching

Girish R Mood, MBBS, MD, MRCS Fellow, Department of Vascular Medicine, Cleveland Clinic Foundation


James Naidich, MD Residency Director, North Shore University Hospital; Professor, Department of Radiology,New York University School of Medicine


Jason J Naidich, MD Assistant Professor of Radiology, New York University School of Medicine; AttendingPhysician, Division of Vascular and Interventional Radiology, North Shore University Hospital


Vincent Lopez Rowe, MD Associate Professor of Surgery, Department of Surgery, Division of Vascular Surgery,University of Southern California Medical Center

Vincent Lopez Rowe, MD is a member of the following medical societies: American College of Surgeons,American Heart Association, Pacific Coast Surgical Association, Peripheral Vascular Surgery Society, Society forClinical Vascular Surgery, Society for Vascular Surgery, and Western Vascular Surgical Society


Miguel A Schmitz, MD Consulting Surgeon, Department of Orthopedics, Klamath Orthopedic and Sports MedicineClinic

Miguel A Schmitz, MD is a member of the following medical societies: American Academy of OrthopaedicSurgeons, American Orthopaedic Society for Sports Medicine, Arthroscopy Association of North America, andNorth American Spine Society


Donald Schreiber, MD, CM Associate Professor of Surgery (Emergency Medicine), Stanford University School of


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Medicine

Donald Schreiber, MD, CM is a member of the following medical societies: American College of EmergencyPhysicians

Disclosure: Abbott Point of Care Inc Research Grant and Speakers Bureau Speaking and teaching; NanosphereInc Grant/research funds Research; Singulex Inc Grant/research funds Research; Abbott Diagnostics IncGrant/research funds None

William A Schwer, MD Professor, Department of Family Medicine, Rush Medical College; Chairman, Departmentof Family Medicine, Rush-Presbyterian-St Luke's Medical Center

William A Schwer, MD is a member of the following medical societies: American Academy of Family Physicians


Gary Setnik, MD Chair, Department of Emergency Medicine, Mount Auburn Hospital; Assistant Professor, Divisionof Emergency Medicine, Harvard Medical School

Gary Setnik, MD is a member of the following medical societies: American College of Emergency Physicians,National Association of EMS Physicians, and Society for Academic Emergency Medicine

Disclosure: SironaHealth Salary Management position; South Middlesex EMS Consortium Salary Managementposition; ProceduresConsult.com Royalty Other

Gary P Siskin, MD Professor and Chairman, Department of Radiology, Albany Medical College

Gary P Siskin, MD is a member of the following medical societies: American College of Radiology, Cardiovascularand Interventional Radiological Society of Europe, Radiological Society of North America, and Society ofInterventional Radiology


Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center Collegeof Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Wai Hong Wilson Tang, MD Associate Professor of Medicine, Section of Heart Failure and CardiacTransplantation Medicine, Cleveland Clinic Foundation

Wai Hong Wilson Tang, MD is a member of the following medical societies: American College of Cardiology,American Heart Association, Heart Failure Society of America, and International Society for Heart and LungTransplantation

Disclosure: Abbott Laboratories Grant/research funds Research Supplies; Medtronic Inc Consulting fee Consulting;St Jude Medical Consulting fee Consulting

Anthony Watkinson, MD Professor of Interventional Radiology, The Peninsula Medical School; Consultant andSenior Lecturer, Department of Radiology, The Royal Devon and Exeter Hospital, UK

Anthony Watkinson, MD is a member of the following medical societies: Radiological Society of North America,Royal College of Radiologists, and Royal College of Surgeons of England


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