Deep venous thrombosis

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29/10/2012 Deep Venous Thrombosis

1/29 emedicine.medscape.com/article/1911303-ov erv iew

Deep Venous Thrombosis

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

Updated: Dec 16, 2011

Background

Deep 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 Eber papyrus, which dates from 1550 BC and documents the potentially fatal hemorrhage that may ensue fromsurgery on varicose veins In 1644, Schenk first observed venous thrombosis when he described an occlusion in

the inferior vena cava 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

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DVT most commonly involves the deep veins of the leg or arm, often resulting in potentially life-threatening emboli

to the lungs or debilitating valvular dysfunction and chronic leg swelling Over the past 25 years, the

pathophysiology of DVT 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

Each year in the United States, more than 200,000 people develop venous thrombosis; of those, 50,000 cases arecomplicated by PE.[1] Lower-extremity DVT is the most common venous thrombosis, with a prevalence of 1 caseper 1000 population In addition, it is the underlying source of 90% of acute PEs, which cause 25,000 deaths peryear in the United States (National Center for Health Statistics [NCHS], 2006) (See Epidemiology.)

Conclusive diagnosis has historically required invasive and expensive venography, which is still considered the

criterion standard The diagnosis may also be obtained noninvasively by means of ultrasonographic examination.(See Workup.)

Early recognition and appropriate treatment of DVT and its complications can save many lives (See Treatment

and Management.) 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.[2, 3, 4, 5, 6]

Anatomy

The peripheral venous system functions both as a reservoir to hold extra blood and as a conduit to return blood

from the periphery to the heart and lungs Unlike arteries, which possess 3 well-defined layers (a thin intima, a

well-developed muscular media, and a fibrous adventitia), most veins are composed of a single tissue layer Onlythe largest veins possess internal elastic membranes, and this layer is thin and unevenly distributed, providing

little buttress against high internal pressures The correct functioning of the venous system depends on a complexseries of valves and pumps that are individually frail and prone to malfunction, yet the system as a whole performsremarkably 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.These suprafascial collecting veins can dilate to accommodate large volumes of blood with little increase in backpressure so that the volume of blood sequestered within the venous system at any moment can vary by a factor of

2 or more without interfering with the normal function of the veins Suprafascial collecting veins belong to the

superficial venous system

Outflow from collecting veins is via secondary conduit veins that have thicker walls and are less distensible Most

of these veins are subfascial and are surrounded by tissues that are dense and tightly bound These subfascial

veins belong to the deep venous system, through which all venous blood must eventually pass through on its wayback to the right atrium of the heart The lower limb deep venous system is typically thought of as 2 separate

systems, one below the 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

tibial veins, draining the sole of the foot; and the peroneal veins, draining the lateral aspect of the foot Venous

sinusoids within the calf muscle coalesce to form soleal and gastrocnemius intramuscular venous plexuses, whichjoin the peroneal veins in the mid calf These veins play an important role in the muscle pump function of the calf.Just below the 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 asthe “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 pumpinghas started, the pressure is neutral and equal everywhere throughout the system and the calf fills with blood,

typically 100-150 mL When the calf contracts, the feeding perforator vein valves are forced closed and the outflowvalves are forced open driving the blood proximally When the calf is allowed to relax, the veins and sinusoids refillfrom the superficial venous system via perforating veins, and the outflow valve is then forced shut, preventing

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retrograde flow With each “contraction,” 40-60% of the calf’s venous volume is driven proximally.[7]

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

is sometimes 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 notpart of the superficial venous system This incorrect term does not appear in any definitive anatomic atlas, yet it

has come into common use in vascular laboratory practice Confusion arising from use of the inappropriate namehas been responsible for many cases of clinical mismanagement and death.) In theproximal thigh,the femoral veinand the deep femoral vein unite to form the common femoral vein, which passes upwards above the groin crease tobecome the iliac vein

The external iliac vein is the continuation of the femoral vein as it passes upward behind the inguinal ligament Atthe level of the sacroiliac joint, it unites with the hypogastric vein to form the common iliac vein The left commoniliac is longer than the right and more oblique in its course, passing behind the right common iliac artery This

anatomic asymmetry sometimes results in compression of the left common iliac vein by the right common iliac

artery to produce May-Thurner syndrome, a left-sided iliac outflow obstruction with localized adventitial fibrosis andintimal proliferation, often with associated deep venous thrombosis At the level of the fifth lumbar vertebra, the 2common iliac veins come together at an acute angle to form the inferior vena cava

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

Pathophysiology

Over 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

to be 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

thrombus that forms may then grow and propagate Endothelial (intimal) damage in the blood vessel may be

intrinsic or secondary to external trauma It may result from accidental injury or surgical insult A hypercoagulablestate can occur due to a biochemical imbalance between circulating factors This may result from an increase incirculating tissue activation 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 the

development of venous thrombosis The origin of venous thrombosis is frequently multifactorial, with components ofthe Virchow triad assuming variable importance in individual patients, but the end result is early thrombus

interaction with the endothelium This interaction stimulates local cytokine production and facilitates leukocyte

adhesion to the endothelium, both of which promote venous thrombosis Depending on the relative balance

between activated coagulation and thrombolysis, thrombus propagation occurs

Decreased vein wall contractility and vein valve dysfunction contribute to the development of chronic venous

insufficiency The rise in ambulatory venous pressure causes a variety of clinical symptoms of varicose veins,

lower extremity edema, and venous ulceration

Development of thrombosis

Thrombosis is the homeostatic mechanism whereby blood coagulates or clots, a process crucial to the

establishment of hemostasis after a wound It may be initiated via several pathways, usually consisting of

cascading activation of enzymes that magnify the effect of an initial trigger event A similar complex of events

results in fibrinolysis, or the dissolution of thrombi The balance of trigger factors and enzymes is complex

Microscopic thrombus formation and thrombolysis (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 relevant deep venous thrombosis is the persistent formation of macroscopic

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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

production of a fibrin clot These steps are controlled by a number of relatively inactive cofactors or zymogens,

which, when activated, promote or accelerate the clotting process These reactions usually occur at the

phospholipid surface of platelets, endothelial cells, or macrophages Generally, the initiation of the coagulation

process can be divided into 2 distinct pathways, an intrinsic system and an extrinsic system (see the image

below)

Coagulation pathw ay.

The extrinsic system operates as the result of activation by tissue lipoprotein, usually released as the result of

some mechanical injury or trauma The intrinsic system usually involves circulating plasma factors Both of thesepathways come together at the level of factor X, which is activated to form factor Xa This in turn promotes the

conversion of prothrombin to thrombin (factor II) This is the key step in clot formation, for active thrombin is

necessary for the transformation 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 restorethe normal blood flow by lysing the fibrin deposit Circulating fibrinolysins perform this function Plasmin digests

fibrin and also 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 factor

inhibition pathways When trauma occurs, or when surgery is performed, circulating ATIII is decreased This hasthe effect of potentiating the coagulation process Studies have demonstrated that levels of circulating ATIII is

decreased more, and stay reduced longer, after total hip replacement (THR) than after general surgical cases (seethe image below)

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 A disturbance in this equilibrium may result in the coagulation process occurring at an inopportune

time or location or in an excessive manor Alternatively, failure of the normal coagulation mechanisms may lead tohemorrhage

Thrombus usually forms behind valve cusps or at venous branch points, most of which begin in the calf

Venodilation may disrupt the endothelial cell barrier and expose the subendothelium Platelets adhere to the

subendothelial surface by means of von Willebrand factor or fibrinogen in the vessel wall Neutrophils and plateletsare activated, releasing procoagulant and inflammatory mediators Neutrophils also adhere to the basement

membrane and migrate into the subendothelium Complexes form of the surface of platelets and increase the rate

of thrombin generation and fibrin formation Stimulated leukocytes irreversibly bind to endothelial receptors and

extravasate into the vein wall by means of mural chemotaxis Because mature thrombus composed of platelets,

leukocytes and fibrin develops, and an active thrombotic and inflammatory process occurs at the inner surface ofthe vein, and an active inflammatory response occurs in the wall of the vein.[8, 9]

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.[10, 11] 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.[12, 13] Although, patients that are immobilized for

long periods of time seem to be at high risk for the development of venous thrombosis, an additional stimulus is

required to develop DVT

Evolution of venous insufficiency

Over time, thrombus organization begins with the infiltration of inflammatory cells into the clot This results in a

fibroelastic intimal thickening at the site of thrombus attachment in most patients and a fibrous synechiae in up to11%.[14] In many patients, this interaction between vessel wall and thrombus leads to valvular dysfunction and

overall vein wall fibrosis Histological examination of vein wall remodeling after venous thrombosis has

demonstrated an imbalance in connective tissue matrix regulation and a loss of regulatory venous contractility thatcontributes to the development of chronic venous insufficiency.[15, 16] Some form of chronic venous insufficiency

develops in 29-79% of patients with an acute DVT, while ulceration is noted in 4-6%.[17, 18] The risk has been

reported to be 6 times greater in those patients with recurrent thrombosis.[19]

Over a few months, most acute DVTs evolve to complete or partial recanalization, and collaterals develop (see theimages below).[20, 21, 22, 23, 24, 25] Although blood flow may be restored, residual evidence of thrombus or stenosis

is observed in half the patients after 1 year Furthermore, the damage to the underlying valves and those

compromised by peripheral dilation and insufficiency usually persists and may progress Venous stasis, venous

reflux, and chronic edema are common in patients who have had a large DVT.[26]

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Low er-extremity venogram show s outlining of an acute deep venous thrombosis in the popliteal vein w ith contrast enhancement.

Low er-extremity venogram show s a nonocclusive chronic thrombus The superficial femoral vein (lateral vein) has the appearance of 2 parallel veins, w hen in fact, it is 1 lumen containing a chronic linear thrombus Although the chronic clot is not obstructive after it

recanalizes, it effectively causes the venous valves to adhere in an open position, predisposing the patient to reflux in the involved

segment.

The acute effect of an occluded outflow vein may be minimal if adequate collateral pathways exist As an

alternative, it may 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 thevalves nonfunctional (because the leaflets no longer coapt), and it forces the blood retrograde through the perforatorbranches and into the superficial system This high-pressure flow may cause dilation of the superficial (usually

low-pressure) system and produce superficial venous incompetence In clinical terms, the increased incidence ofreflux in the ipsilateral greater saphenous vein increases 8.7-fold on follow-up of DVT.[20] This chain of events (ie,obstruction to antegrade flow producing 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

valves and venous wall are altered by organization and ingrowth of smooth muscle cells and production of

neointima This process leaves damaged, incompetent, underlying valves, predisposing them to venous reflux Themural inflammatory reaction breaks down collagen and elastin, leaving a noncompliant venous wall.[20, 21, 22, 23, 24,

oxygenation, and ulceration may result After venous insufficiency occurs, no treatment is ideal; elevation and use

of compression stockings may compensate, or surgical thrombectomy or venous bypass may be attempted.[27,

28, 29, 30]

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With anticoagulation alone, as many as 75% of patients with symptomatic DVT present with PTS at 5-10

years.[30, 31] However, the incidence of venous ulceration is far less, at 5% Of the half million patients with venousulcers in the United States, 17-45% report having a history of DVT.[32]

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

thrombi represent 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 slowsand even stops in some areas, predisposing patients to thrombosis.[33]

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

symptomatic calf vein DVT extend to the proximal veins.[34] 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 untreated proximal thrombi is 29-50%.[35, 34] Most PEs are first diagnosed at autopsy.[36, 37]

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.[38] Paget in England andvon Schrötter in Germany independently described effort thrombosis more than 100 years ago In this primary form

of the disease, an underlying chronic venous compressive abnormality caused by the musculoskeletal structures

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

This contrast-enhanced study w as obtained through a Mediport placed through the chest w all through the internal jugular vein to

facilitate chemotherapy A thrombus has propagated peripherally from the tip of the catheter in the superior vena cava into both

subclavian veins.

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Superior vena cava syndrome in a patient w ith lung cancer CT scan demonstrates a hypoattenuating thrombus that fills the superior

vena cava The patient w as treated w ith anticoagulation alone.

In 75% of patients with secondary thrombosis, hypercoagulability and/or indwelling central venous catheters are

important contributing factors In fact, with the advent of central venous catheters, upper-extremity and

brachiocephalic venous thrombosis has become a more common problem.[39, 40, 41, 42]

For more information on upper-extremity DVT, see the eMedicine article in the Radiology Journal

pulmonary emboli; however, the single largest autopsy series ever performed to specifically to look for the source

of fatal PE was performed by Havig in 1977, who found that one third of the fatal emboli arose directly from the calfveins.[45]

Etiology

Numerous 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 acute provoking 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 venous

obstruction Immobility can be as transient as that occurring during a transcontinental airplane flight or that during

an operation under general anesthesia It can also be extended, as during hospitalization for pelvic, hip, or spinalsurgery, or due to stroke or paraplegia Individuals in these circumstances warrant surveillance, prophylaxis, andtreatment if they develop DVT.[46, 47]

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

Increased central venous pressure, either mechanical or functional, may reduce the flow in the veins of the leg

Mass effect on the iliac veins or inferior vena cava from neoplasm, pregnancy, stenosis, or congenital anomaly

increases outflow 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

venous stasis In iliocaval thromboses, an underlying anatomic contributor is identified in 60-80% of patients Thebest-known anomaly is compression of left common iliac vein at the anatomic crossing of the right common iliacartery The vein normally 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 called May-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

or atrophy of paired supracardinal and subcardinal veins Anomalous embryologic development may result in

absence of the normal cava These variations may increase the risk of symptoms because small-caliber vesselsmay be most subject to obstruction In patients younger than 50 years who have deep venous thrombosis, the

incidence of a caval anomaly is as high as 5%.[48]

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incidence of a caval anomaly is as high as 5%.[48]

A double or duplicated inferior vena cava results from lack of atrophy in part of the left supracardinal vein, resulting

in a duplicate structure to the left of the aorta The common form is a partial paired inferior vena cava that connectsthe left common iliac and left renal veins When caval interruption, such as placement of a filter, is planned, thesealternate pathways must be considered As an alternative, the inferior vena cava may not develop The most

common alternate route for blood flow is through the azygous vein, which enlarges to compensate If a venous

stenosis is present at the communication of iliac veins and azygous vein, back pressure can result in

insufficiency, stasis, or thrombosis.[49]

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

venous drainage to the atrium is patent Because this pathway involves small hemorrhoidal vessels, thrombosis ofthese veins can 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 and

extension 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 retroperitoneal

fibrosis.[50, 51]

Mechanical injury to vein

Mechanical injury to the vein wall appears to provide an added stimulus for venous thrombosis Hip arthroplasty

patients 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

the calf.[52] 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

be obscure, 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 acuteurinary tract or 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

logistic regression analysis found the following factors to be significantly and independently associated with an

increased risk for VTE, most of which were asymptomatic and diagnosed by venography of both lower

extremities[53] :

Presence of an acute infectious disease

Age older than 75 years

Cancer

History of prior VTE

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

of all DVT (with an incidence of 1 case per 100 population).[36, 54]

The single most powerful risk marker remains a prior history of DVT with as many as 25% of acute venous

thrombosis occurring in such patients.[55] Pathologically, remnants of previous thrombi are often seen within the

specimens of new acute 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 coagulation cascade Deficiencies of protein C, protein S, or antithrombin III account for

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mutations within the coagulation cascade Deficiencies of protein C, protein S, or antithrombin III account for

approximately 5-10% of all cases of DVT.[56]

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

thrombogenic risk factors occurring in the elderly than in those younger than 40 years.[55, 57] Venous stasis, asseen in immobilized patients and paralyzed limbs, also contributes to the development of venous thrombosis

Autopsy studies parallel the duration of bed rest to the incidence of venous thrombosis, with 15% of patients in

those studies dying within 7 days of bedrest to greater than 80% in those dying after 12 weeks.[10] Within strokepatients, DVT is found in 53% of paralyzed limbs, compared with only 7% on the nonaffected side.[58]

Malignancy is noted in as many as 30% of patients with venous thrombosis.[55, 59] The thrombogenic mechanismsinvolve abnormal coagulation, as evidenced by 90% of cancer patients having some abnormal coagulation

factors.[60] Chemotherapy may increase the risk of venous thrombosis by affecting the vascular endothelium,

coagulation cascades, and tumor cell lysis The incidence has been shown to increase in those patients

undergoing longer courses of therapy for breast cancer, from 4.9% for 12 weeks of treatment to 8.8% for 36

weeks.[61] Additionally, DVT complicates 29% of surgical procedures done for malignancy.[62]

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%,

whereas orthopedic hip surgery can occur in up to 50% of patients.[63] 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 various disease states.[64] For more information, see the eMedicine article Deep Venous

Thrombosis Prophylaxis in Orthopedic Surgery in the Orthopedic Surgery Journal

Based on radioactive labeled fibrinogen, about half of lower extremity thrombi develop intraoperatively.[65]

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

surgical venous thrombosis

XI, and prothrombin Resistance of procoagulant factors to an intact anticoagulation system has also recently

been described with the recognition of factor V Leiden mutation, representing 10-65% of patients with DVT.[69] Inthe setting of venous stasis, these factors are allowed to accumulate in thrombosis prone sites, where mechanicalvessel injury has occurred, stimulating the endothelium to become prothrombotic.[70]

Factor V Leiden is a mutation that results in a form of factor Va that resists degradation by activated protein C,

leading to a hypercoagulable state Its importance lies in the 5% prevalence in the American population and its

association with a 3-fold to 6-fold increased risk for VTE Antiphospholipid syndrome is considered a disorder ofthe immune system, where antiphospholipid antibodies (cardiolipin or lupus anticoagulant antibodies) are

associated with a syndrome of hypercoagulability Although not a normal blood component, the antiphospholipidantibody may be asymptomatic It is present in 2% of the population, and it may be detected in association withinfections or the administration of certain drugs, including antibiotics, cocaine, hydralazine, procainamide, and

quinine.[67]

Tests for these genetic defects are often not performed in patients with recurrent venous thrombosis because

therapy remains symptomatic In most patients with these genetic defects, lifetime anticoagulation therapy withwarfarin or low molecular weight heparin (LMWH) is recommended after recurrent DVT without an alternative

identifiable etiology documented The risk of recurrent DVT is multiplied 1.4-2 times, with the most common

genetic polymorphisms predisposing individuals to DVT However, the low incidence of factor V Leiden and

prothrombin G20210A may not warrant aggressive prophylaxis Therefore, genetic testing might not be warranted

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until a second event occurs.[71]

Other conditions that can induce hypercoagulability

Other diseases and states can induce hypercoagulability in patients without other underlying risks for DVT Theycan predispose patients to DVT, though their ability to cause DVT without intrinsic hypercoagulability is in

question The conditions include malignancy, dehydration, and use of medications (eg, estrogens) Acute

hypercoagulable states also occur, as in disseminated intravascular coagulopathy (DIC) resulting from infection orheparin-induced thrombocytopenia.[72]

Summary of risk factors

A summary of risk factors is as follows:

Age

Immobilization longer than 3 days

Pregnancy and the postpartum period

Major surgery in previous 4 weeks

Long plane or car trips (>4 h) in previous 4 weeks

Cancer

Previous DVT

Stroke

Acute myocardial infarction (AMI)

Congestive heart failure (CHF)

Lower extremity fractures

Systemic lupus erythematosus (SLE) and the lupus anticoagulant

Behçet syndrome

Homocystinuria

Polycythemia rubra vera

Thrombocytosis

Inherited disorders of coagulation/fibrinolysis

Antithrombin III deficiency

Protein C deficiency

Protein S deficiency

Prothrombin 20210A mutation

Factor V Leiden

Dysfibrinogenemias and disorders of plasminogen activation

Intravenous (IV) drug abuse

Oral contraceptives

Estrogens

Heparin-induced thrombocytopenia (HIT)

Epidemiology

DVT 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 studiesare limited by the inherent inaccuracy of clinical diagnosis Existing data that probably underestimate the true

incidence of DVT suggest that about 80 cases per 100,000 population occur annually Approximately 1 person in

20 develops a DVT in the course of his or her lifetime About 600,000 hospitalizations per year occur for DVT in theUnited States

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In elderly persons, the incidence is increased 4-fold The in-hospital case-fatality rate for VTE is 12%, rising to

21% in elderly persons In hospitalized patients, the incidence of venous thrombosis is considerably higher andvaries from 20-70% Venous ulceration and venous insufficiency of the lower leg, which are long-term

complications of DVT, affect 0.5% of the entire population Extrapolation of these data reveals that as many as 5million people have venous stasis and 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

in both 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

Prevalence of deep venous thrombosis by race

From a demographic viewpoint, Asian and Hispanic populations have a lower risk of VTE, whereas whites and

blacks have a higher risk (2.5-4 times higher)

Prognosis

Most DVT is occult and usually resolves spontaneously without complication The principal long-term morbidity

from DVT is PTS, which complicates about a quarter of cases of symptomatic proximal DVT; most cases developwithin 2 years afterward

Death from DVT is attributed to massive PE, which causes as many as 300,000 deaths annually in the United

States.[73] PE is the leading cause of preventable in-hospital mortality The Longitudinal Investigation of

Thromboembolism Etiology (LITE) that combined data from two prospective cohort studies, the Atherosclerosis

Risk in Communities (ARIC) and the Cardiovascular Health Study (CHS) determined the incidence of symptomaticDVT and pulmonary embolism in 21,680 participants aged 45 years or older who were followed for 7.6 years.[74]

Kaushal (Kevin) Patel, MD Vascular Surgeon, Kaiser Permanente Los Angeles Medical Center

Disclosure: Nothing to disclose

Coauthor(s)

Marc 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

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

Trang 13

John J Borsa, MD is a member of the following medical societies: American College of Radiology, American

Society of Neuroradiology, Cardiovascular and Interventional Radiological Society of Europe, Radiological

Society of North America, Royal College of Physicians and Surgeons of Canada, and Society of InterventionalRadiology

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

Medical Center

Hearns W Charles, MD is a member of the following medical societies: American College of Radiology,

American Roentgen Ray Society, Radiological Society of North America, and Society of Cardiovascular and

Interventional Radiology

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,

American Heart Association, American Medical Association, American Roentgen Ray Society, Association ofUniversity Radiologists, and Radiological Society of North America

Linda J Chun, MD Resident Physician, Department of Surgery, Los Angeles Medical Center, Kaiser

Permanente

Douglas M Coldwell, MD, PhD Professor of Radiology, Director, Division of Vascular and Interventional

Radiology, 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,

and Special Operations Medical Association

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

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

Orthopaedic Surgeons, 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

School of 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

Luis G Fernandez, MD, KHS, FACS, FASAS, FCCP, FCCM, FICS Assistant Clinical Professor of Surgery

Trang 14

and Family 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 Surgical Critical Care Unit, Trinity Mother Francis Health System; Brigadier General, Texas MedicalRangers, 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 of Legal Medicine, American College of Surgeons, American Society of Abdominal Surgeons, AmericanSociety of General Surgeons, American Society of General Surgeons, American Society of Law, Medicine &

Ethics, American Trauma Society, Association for Surgical Education, Association of Military Surgeons of the

US, Chicago Medical Society, Illinois State Medical Society, International College of Surgeons, New York

Academy of Sciences, Pan American Trauma Society, Society of Critical Care Medicine, Society of

Laparoendoscopic Surgeons, Southeastern Surgical Congress, Texas Medical Association, and Undersea andHyperbaric 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,

American Institute of Ultrasound in Medicine, American Medical Association, Association for Academic

Surgery, Phi Beta Kappa, 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 Gastrointestinal

Medicine, 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 Gastroenterological

Association, 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

Alimentary Tract

Disclosure: AMGEN Royalty Consulting; ARdelyx Ownership interest Board membership

Harris Gellman, MD Consulting Surgeon, Broward Hand Center; Voluntary Clinical Professor of Orthopedic

Surgery and Plastic Surgery, Departments of Orthopedic Surgery and Surgery, University of Miami, Leonard MMiller School 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 of the 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

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