rivaroxaban showed statically less intracranial bleeding or fatal bleeding.

Apixaban is currently FDA approved for the prevention of complications of atrial fibrillation, for

prophylaxis of DVT following hip or knee replacement surgery, for the treatment of DVT/PE, and for

reduction in the risk of recurrence of DVT/PE. This agent has been evaluated in six studies involving

VTE, noninferior in two, superior in three, and a failure in one. In a recent study, Apixaban was given

for 7 days of initial treatment for DVT, followed by a lower dose bid versus standard enoxaparin

followed by warfarin for 6 months. Apixaban was noninferior to standard therapy with less bleeding.59

Apixaban was also studied as extended treatment of VTE.60 After a standard duration of treatment, an

additional 12 months of apixaban therapy compared to placebo revealed a significant decrease in the

rate of VTE without an increase in bleeding. This is the only new oral agent that has revealed

superiority to standard therapy without an increase in bleeding in atrial fibrillation patients. Edoxaban

administered once daily after initial treatment with heparin was noninferior to high-quality standard

therapy and caused significantly less bleeding in a broad spectrum of patients with VTE, including those

with severe PE.61 Problems with these new agents include the difficulty at the present time to reliably

reverse the anticoagulant effects of these drugs with only one approved medication available at the

present time, the fact that there is little data available on bridging of these agents when other

procedures need to be performed, and the fact that they are nongeneric. Their usefulness for VTE will

dramatically improve when adequate reversal agents become clinically available.62 The use of P-selectin

inhibitors, an area of ongoing research, uses an anti-inflammatory approach to limit thrombus

amplification without causing anticoagulation.

NONPHARMACOLOGIC TREATMENTS

Postthrombotic syndrome (PTS) results from loss of competence of the venous valves as a result of DVT

or persistent venous obstruction, or a combination of both. It can cause significant morbidity in the

form of pain, swelling, skin breakdown, and ulcerations. A Cochrane meta-analysis found a strong effect

(OR 0.31) for prevention of PTS using graduated compression stockings beginning within 2 weeks of

onset of DVT, with important data highlighted from two open-labeled randomized single-center studies

that utilized stockings of 30 to 40 mm Hg for 2 years after DVT.63 From these data, stockings of 30 to

40 mm Hg gradient should be recommended to most patients with DVT, for a minimum of 2 years postDVT, and longer if they have symptoms of PTS. There is a new study that would suggest that stockings

may not prevent PTS after a first proximal DVT.64 However, there are a number of specific

considerations in this study that will need to be repeated before the recommendation of stockings after

DVT is reversed. In addition, ambulation with good compression does not increase the risk of PE, while

significantly decreasing the incidence and severity of the PTS.65,66 Early ambulation has the potential to

decrease PTS and improve patients’ quality of life (QOL). Thus, patients should be encouraged to

ambulate as part of their post-DVT care recommendations.31

IVC Filters

The traditional indications for the use of IVC filters include a complication of anticoagulation, a

contraindication to anticoagulation, and failure of anticoagulation. Protection from PE has been greater

than 95% using cone-shaped wire-based permanent IVC filters.67 Cone-shaped filters have a lower

incidence of IVC thrombosis compared with basket-shaped filters, and a recent study between the two

filter types was stopped early because of the high rate of IVC thrombosis with the basket-shaped

device.68 The success achieved with filters has expanded the indications, including free-floating

thrombus longer than 5 cm, when bleeding risk with anticoagulation is excessive, when the risk of PE is

felt to be very high, and to allow for the use of perioperative epidural anesthesia.69–71 Filters can be

permanent or optional (retrievable). If a retrievable filter is left in to become a permanent filter, the

long-term fate of that filter has yet been defined.

Filters are usually placed in an infrarenal location. However, they may also be placed in the

suprarenal location or in the superior vena cava. Indications for suprarenal placement include high-lying

clot, pregnancy, women of childbearing potential, or a previous device that has failed or become filled

with clot. Sepsis is not a contraindication to the use of wire-based filters since the trapped material can

be sterilized with antibiotics. Although filters have been placed under x-ray guidance, percutaneous

techniques for filter insertion using bedside external ultrasound or intravascular ultrasound are now

being recommended. Transabdominal external ultrasound is difficult in the face of morbid obesity,

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overlying bowel gas, or open abdominal wounds. In these instances, intravascular ultrasound has been

found to be more successful.72 Other than one randomized prospective study on the use of filters as

treatment of DVT (which is not how filters are traditionally used), evidence for the use of filters is

given a 2C level of evidence.73,74

Thrombolytic and Surgical Procedures for Deep VTE

For DVT treatment, the goals are to prevent extension or recurrence of DVT, prevent PE, and minimize

the late squeal of thrombosis, namely CVI. Standard anticoagulants accomplish the first two goals but

not the third goal. The PTS (venous insufficiency related to venous thrombosis) occurs in up to 30% of

patients after DVT and even greater with more proximal iliofemoral DVT.27 Experimentally, prolonged

contact of the thrombus with the vein wall increases damage.75 The thrombus initiates an inflammatory

response in the vein wall that can lead to vein wall fibrosis and valvular dysfunction. Systemic

thrombosis in two small series revealed a decrease in the incidence of CVI with streptokinase, as

opposed to systemic unfractionated heparin (UFH). However, results depend on complete thrombolysis.

Because of this inability to predict complete lysis, combined with its bleeding potential thrombolysis is

recommended infrequently. However, urokinase administered directly into venous thrombi has led to an

increase in enthusiasm and the publication of a national thrombolysis registry.76,77 In 473 patients, 287

of whom underwent follow-up, 312 urokinase infusions in 303 limbs were reported. Venous thrombi

occurred in the iliofemoral segment in 71% of cases alone, without IVC involvement in 79%, and

including the IVC in 21% of cases. Patients had acute disease in approximately two-thirds of cases, 16%

had chronic disease, and 19% had combined acute and chronic disease. Approximately 30% had prior

DVT. Complete thrombolysis was achieved in 31% and partial lysis in 52% of cases. The mean amount

of urokinase used was 7.8 million units, and the mean time of infusion was 53.4 hours. Successful lysis

was predicted by acute DVT and no history of prior DVT. Complications included major bleeding

necessitating blood products in 11% and minor bleeding in 16%. Mortality rate was 0.4%, intracranial

hemorrhage rate was 0.2%, and subdural hemorrhage rate was 0.2%. Total lysis was noted in only 31%

of the entire series; however, in patients with acute iliofemoral DVT, no previous symptoms, and the

use of the popliteal vein access site, total lysis was more frequent. At 12 months, patency was 79% if

lysis was complete, 58% with greater than 50% lysis, and 32% with less than 50% lysis. Absence of

valvular reflux was found in 72% of cases with complete lysis, whereas overall valvular reflux was seen

in 58% of cases.

Importantly, aggressive therapies have been found to improve QOL. A small randomized study

demonstrated that thrombolysis is superior to anticoagulation in patients with iliofemoral DVT.78

Results appear to be optimized further by combining catheter-directed thrombolysis with mechanical

devices, including the AngioJetTM rheolytic catheter, and the EKOS MicroSonicTM accelerated

thrombolysis catheter. In addition, new devices (such as the Angiovac) are being developed specifically

for large veins. With these devices, thrombolysis is hastened, the amount of thrombolytic agent is

decreased, and bleeding is thus decreased. Importantly, a number of small studies have reported a

decrease in PTS with catheter-directed thrombolysis for iliofemoral DVT79 and long-term results have

demonstrated patency rates over 80% with competent valves.80 Postthrombotic morbidity correlates

with residual thrombus.81 In addition, the use of venous stents for iliac venous obstruction has been

shown to decrease the incidence of PTS and CVI.82 To more fully elucidate the role of aggressive

therapy in proximal iliofemoral venous thrombosis, a study is in progress, supported by the National

Institutes of Health, to compare catheter-directed pharmacomechanical thrombolysis to standard

anticoagulation for significant iliofemoral venous thrombosis, with both arms also undergoing

ambulation and stocking use. This study, the Attract Trial, will evaluate anatomic, physiologic, and QOL

endpoints in addition to vascular laboratory endpoints and a careful evaluation of complications.

Thrombolytic therapy for PE remains controversial. Although agents lyse thrombus effectively,

recurrence rates and patient mortality rate were not reduced. However, the original studies were not

powered to address this outcome. Results are best if patients are young, the embolus is less than 48

hours old, and the embolus is large. Streptokinase, urokinase, and tissue plasminogen activator have all

been used.83 All agents rapidly dissolve clot, but by 7 days, the advantages for all three agents decrease.

The benefit of thrombolytic agents for PE thus appears to be greatest in patients who would die as a

result of massive PE in the first hour after the PE occurs, which can occur in up to 10% of cases.

However, more recent data suggest that thrombolysis may be useful in patients with right ventricular

dysfunction without hemodynamic instability and it has been suggested that thrombolysis will improve

outcomes if patients have evidence of right-sided heart changes.84–89 In addition, thrombolysis therapy

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has been recommended in patients without hypertension who are judged to have a low risk of

bleeding.73

Contributions to thrombolytic therapy include:

Absolute

neurosurgery within 3 months

active internal bleeding

recent (<2 months) cerebrovascular accident

intracranial disease

recent gastrointestinal bleeding

Relative Major

recent (<10 days) major surgery, obstetric delivery, or organ biopsy

left-sided heart thrombus

active peptic ulcer or gastrointestinal abnormality

recent major trauma

uncontrolled hypertension (systolic >180 mm Hg; diastolic >110 mm Hg)

recent eye surgery

Relative Minor

minor surgery or trauma

recent cardiopulmonary resuscitation

atrial fibrillation with mitral valve disease

bacterial endocarditis

hemostatic defects (i.e., renal or liver disease)

Venous Thrombectomy

Iliofemoral venous thrombectomy has been advocated to prevent impending venous gangrene. This

technique results in mechanical clearing of the venous circulation and may be combined with a

temporary arteriovenous fistula. Thrombectomy uses a Fogarty balloon catheter passed from the

femoral vein during Valsalva maneuvers. An arteriovenous fistula is constructed so that it can be taken

down by nonsurgical techniques. Complete venography in the operating room is recommended, as backbleeding is unreliable for the assessment of complete thrombus clearance. Thrombosis recurrence rates

less than 20% have been reported. The incidence of PE during the first week after thrombectomy is

equivalent to the incidence with anticoagulation only. The frequency of clinical success has been

reported to be between 42% and 93%.90 The largest series of 77 legs with a follow-up period of

between 5 and 13 years revealed maintenance of patency, but a steady decline in valvular competence

over time.91

In the only comparative study of iliofemoral venous thrombosis treatment comparing thrombectomy

with anticoagulation (31 patients) versus anticoagulation alone (32 patients), iliofemoral vein patency

was improved (76% vs. 35%), femoropopliteal patency was improved (52% vs. 26%), and the clinical

outcome was better at 6 months (40% asymptomatic vs. 7%).91 At 10 years, the number of patients

available for follow-up had decreased to 13 in the thrombectomy group and 17 in the anticoagulationalone group. Patency remained improved in the thrombectomy group (83% vs. 41%), and absence of

popliteal reflux was found in 78% of the thrombectomy-plus-anticoagulation group compared with 43%

of the anticoagulation group alone.

Pulmonary Embolectomy

Surgical approaches for PE are indicated for patients with massive PE with hypotension who require

large doses of vasopressors. These are often patients in whom thrombolytic agents have been

unsuccessful. Open pulmonary embolectomy is associated with high rates of morbidity and mortality.

Today, open pulmonary embolectomy is limited to those who require manual cardiac massage for

hypotension or those in whom catheter pulmonary embolectomy fails. However, there may be a more

expanded role for pulmonary embolectomy in the future.92

Superficial Thrombophlebitis

SVT is a well-recognized clinical entity, characterized by a painful erythematous and palpable cord-liked

structure, usually compromising the lower extremities but capable of affecting any superficial vein in

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the body. Thrombophlebitis is believed to have a multifactorial etiology, in which Virchow triad of

altered blood flow, changes in the vessel wall, and abnormal coagulation are recognized to play a

significant role. SVT has been considered a benign disease requiring only conservative management

with compression, nonsteroidal anti-inflammatory medications, and lower extremity elevation. Recently

SVT, especially above the knee superficial thrombophlebitis, has been reported to coexist with DVT, to

propagate to popliteal or femoral level and to even cause PE.93–97 A medical approach using

anticoagulant therapy appears as the treatment of choice when there is above-knee SVT with deep

venous system involvement.

The incidence of SVT occurs in approximately 125,000 people in the United States per year.98

However, the actual incidence is likely far greater as these statistics may be outdated and many cases go

unreported. Approximately 54% to 65% of the reported cases affect females with an average age of 58

years.93,99 The most frequent predisposing risk factor for SVT is varicose veins, occurring in 62% of

patients. Other risk factors include immobilization, trauma, postoperative states, age >60 years,

obesity, tobacco use, history of DVT or SVT, pregnancy, puerperium, autoimmune disease, use of oral

contraceptives or hormonal replacement therapy, and hypercoagulable state.93,99,100 Hypercoagulable

screening should be considered in patients with ascending or worsening thrombophlebitis despite initial

treatment.101,102 Malignancy has been reported as a risk factor for developing SVT, affecting 13% to

18% of patients.96,103

The overall recurrence of SVT was described as 18% over 15 months, equally frequent in varicose and

nonvaricose phlebitis. Deep venous reflux increases the recurrence rate to 33%, while hypercoagulable

states increase the recurrence rate to 42% over the same period of time.104

The clinical symptoms and signs for SVT are overt. Duplex ultrasound imaging of the affected

extremity should be performed to rule out extension of the process into the deep venous system or

concomitant DVT.101,105 Duplex ultrasound shows the extent of the SVT, its relation to the veins

connecting with the deep vein system, and the presence of concomitant DVT. In addition, duplex

ultrasound allows checking the competence of the valves in the superficial and deep veins.105

Complete thrombophilia workup is not routinely recommended. However, it may be indicated in

selected patients with recurrent primary thrombophlebitis or aggressive thrombophlebitis.105 Screening

for underlying diseases, including malignancy or vasculitis, is performed if signs or symptoms suggest

the presence of such a problem.105

Treatment

Several therapeutic approaches have been proposed for patients with SVT. These include ligation or vein

stripping of the affected vein, elastic stockings, NSAIDs to reduce pain and inflammation, and variable

doses of unfractionated heparin or LMWH followed by oral anticoagulant therapy. There is no consensus

on the optimal treatment of SVT in clinical practice.

The course of treatment for SVT should be tailored accordingly to its location and concomitant DVT if

there is any associated infectious process. Thrombus location in trunks of either the great or small

saphenous vein (SSV) may have the highest risk of extension into the deep vein system and thus require

more aggressive treatment than other locations. The treatment for primary SVT localized in the distal

great saphenous vein (GSV) and tributaries veins consists of ambulation, warm soaks, compression, and

NSAID agents.106,107 If the patient presents risk factors for DVT, pharmacologic prophylaxis should be

considered seriously.105

Titon et al. were among the first to compare different approaches on the medical treatment of SVT.108

In a multicenter study, 117 patients were randomized into 3 groups: fixed dose LMWH calcium

nadroparin (n = 38), adjusted-dose LMWH calcium nadroparin (n = 39), and the NSAID naproxen (n =

40) for 6 days. At day 7, heat and redness were significantly less (P < .001) in both groups treated with

LMWH compared with those given the NSAID. In addition, at 8 weeks, persistence of symptoms and

signs was less frequent in the LMWH-treated groups (P = 0.007). Efficacy did not differ between the

fixed and weight-adjusted doses of LMWH.

The management of SVT was further addressed in a randomized, double-blind study describing 427

patients with documented acute symptomatic SVT of the legs.109 Patients were randomly assigned to

receive 40 mg of enoxaparin sodium subcutaneously; 1.5 mg/kg of enoxaparin sodium subcutaneously;

oral tenoxicam 20 mg; or placebo, all once daily for 8 to 12 days. LMWH was associated with a lower

incidence of SVT extension and/or recurrence, compared with placebo (OR, 0.32; 95% confidence

interval [CI], 0.16 to 0.65, and OR 0.33; 95% CI, 0.16 to 0.68, respectively), without major bleeding or

HIT. There was no statistical difference with respect to 12-day outcomes between the active treatment

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groups. However, there was a trend in favor of the LMWH.

The Vesalio Investigator Group compared two regimens of LMWH with each other.110 A total of 164

patients were enrolled and randomized into 2 groups: prophylaxis group (n = 81) and treatment group

(n = 83). After completion of 3 months, the cumulative rate of SVT progression and VTE complications

did not differ between the prophylactic (8.6%; 95% CI, 3.5 to 17.0) and therapeutic (7.2%; 95% CI, 2.8

to 15.1) groups. No patient in either group developed major bleeding, while one patient in each group

developed a clinically asymptomatic HIT. Clinical symptoms improved to a similar extent in both

groups, and similar rates of minor extension or recurrent thrombophlebitis were observed during the

follow-up period.

Prophylactic dose intravenous (IV) UFH was used as a comparator treatment in two studies.111

Relative to elastic stocking alone, prophylactic IV UFH plus elastic stockings was associated with an

86% reduction in SVT extension and/or recurrence (OR 0.14; 95% CI, 0.03 to 0.67). Marchiori et al.112

compared high-dose versus low-dose IV UFH. A nonsignificant 86% reduction in VTE (OR 0.14; 95% CI

0.02 to 1.23) and a 37% (OR 0.63; 95% CI, 0.21 to 1.88) lower rate of SVT extension and/or recurrence

were observed in those patients treated with high-dose UFH. There were no episodes of major bleeding

and HIT.

LMWH was compared with saphenofemoral disconnection for the treatment of proximal GSV

thrombophlebitis in a prospective, randomized clinical study.113 In this study, 84 consecutive patients

diagnosed as presenting SVT alone were divided into 2 groups treated with saphenofemoral

disconnection under local anesthesia with a short hospital stay (n = 45) or enoxaparin on an outpatient

basis for 4 weeks (n = 39). In all, 30 patients per group completed the study requirements. In the

surgical group, 2 patients (6.7%) presented complications of the surgical wound, 1 (3.3%) had SVT

recurrence, and 2 (6.7%) had nonfatal PE. In the enoxaparin group, there was no progression of the

thrombosis to the deep venous system or PE, there were 2 cases (6.7%) of minor bleeding and 3 (10%)

recurrences of SVT. Even when the study found no statistically significant difference between the 2

groups in the treatment of SVT, the LMWH group demonstrated a significant socioeconomic advantage

and confirmed the efficacy of LMWH treatment in resolving symptoms and signs and preventing DVT

and PE.

Prophylactic-dose LMWH has the advantage over other equally efficacious techniques in resolving

symptoms and signs and preventing DVT and PE in cases without concomitant DVT. Patients treated

with LMWH do not require hospitalization, present less adverse effects, do not require laboratory

monitoring in most situations, and have a low risk of bleeding, and treatment is less expensive if

hospitalization is not required. It is generally felt that medical management with anticoagulants versus

surgical treatment is somewhat superior for minimizing complications and preventing subsequent DVT

and PE development. On the contrary, surgical treatment with ligation at the SFJ combined with

stripping (with or without perforator interruption) appears to minimize superficial venous thrombus

extension, which ultimately provides improved pain relief.114

Septic thrombophlebitis requires treatment with broad-spectrum IV antibiotics. If rapid resolution of

the cellulitis occurs, no treatment beyond a short course of antibiotics and standard treatment for the

superficial thrombophlebitis are required. However, if the patient becomes septic, excision of the

infected vein is required. With positive blood cultures, an extended course of antibiotics specific for the

identified organism is indicated additionally.

The majority of episodes of uncomplicated superficial thrombophlebitis respond to conservative

management. However, the recurrence rate for superficial thrombophlebitis has been estimated

between 15% and 20%.115–117 Finally, in the CALISTO study, fondaparinux was found effective in

limiting a series of endpoints including death, PE, DVT, and extension or recurrence at days 47 and 77

after SVT diagnosis. This was in patients with axial vein SVT of at least 5-cm length with the thrombus

at least 3 cm from the SFJ. Less extensive SVT requires only symptom control with oral or topical

NSAIDs.14

2801

Figure 98-1. Duplex image demonstrating the superficial compartment, which contains the saphenous compartment with great

saphenous vein (GSV) (straight arrow) lying within and the deep compartment with femoral vessels (curved arrow) lying within.

CHRONIC VENOUS DISEASE

Normal Venous Anatomy

The lower extremity venous system is composed of deep, perforating, and superficial veins (Fig. 98-

1).118 The common femoral, femoral, deep (profunda) femoral veins in addition to the popliteal and

tibial/peroneal veins make up the deep system. The once named “superficial” femoral vein has been

changed to simply “femoral vein” to prevent the confusion the term “superficial” implied when

treatment of an actual DVT is required. The deep veins lie beneath the investing fascia of the muscles of

the leg and thigh (the deep compartment). The saphenous veins have similarly undergone a change in

name to the GSV and SSV to standardize the abbreviations that were otherwise extremely confusing. It

has also become clear that the GSV and SSV lie within the subcutaneous tissue and surrounded by a

separate saphenous compartment. The saphenous nerve lies within the GSV compartment below the

knee, which places the nerve at risk of injury during surgery or percutaneous intervention, but if the

associated sensory loss occurs, it appears to have little impact on the patient’s QOL in the long term.119

The sural nerve lies in close proximity to the SSV and within its compartment. The superficial veins that

lie outside the saphenous compartment, but parallel to the GSV or SSV, are called accessory saphenous

veins. The term communicating vein is now reserved for those veins that interconnect with other veins of

the same system, and the term perforating vein is reserved for those that penetrate the muscular fascia to

connect superficial to deep.118 In the past, perforating veins with rather constant anatomic location have

been named after their discoverer (e.g., Crockett’s, Boyd’s perforators), but more descriptive terms

designating location are now preferred.118 An excellent international consensus committee description

of the standardized venous anatomy nomenclature of the leg and pelvic can be found in an article by

Caggiati and colleagues.120

The variability of the lower extremity venous system is well known, but only certain anatomic

variations are of importance for current surgical practice. The popliteal and femoral veins have variable

anatomy and are often duplicated much like the tibial veins. The deep femoral vein often connects

directly or through tributaries to the popliteal vein. Although duplication of the GSV has been estimated

to be present in up to 50% of patients in some studies, it is becoming evident that duplication of the

true GSV lying within the saphenous compartment is much less common.121,122 The SFJ often has at

least four branches in addition to the GSV, but the arrangement and precise location of the branches are

quite variable. The most cephalic branch is generally the superficial epigastric vein and is of some

importance in new techniques for managing GSV reflux since the vein acts as a landmark for

percutaneous interventions and there is a desire to have it remain patent following the procedure. The

SSV is rarely duplicated (4%).123 Although the SSV appears to pierce the deep fascia in the upper third

of the calf, in reality the membranous layer forming the roof of the SSV compartment is thickened while

the muscular fascia disappears, which positions the SSV between the gastrocnemius muscle bellies.123 In

only 62% of limbs does the SSV actually end in the popliteal fossa and can well end above the crease of

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the knee.123 The anatomy of the perforating veins becomes extremely important when considering

surgery aimed at preventing reflux into the lower leg. Certainly, removing the GSV will not prevent the

impact of perforator reflux if one ignores the fact that the posterior tibial perforators (Cockett

perforators of old) connect the posterior accessory GSV with the posterior tibial veins rather than the

GSV proper. Similarly, not recognizing that paratibial perforators exist can result in an unsuccessful

intervention aimed at preventing calf perforator reflux.124

With the exception of foot veins, the valves promote blood flow from superficial to deep and from

caudal to cephalad in direction. The valves are made of a fine connective tissue skeleton covered by

endothelium and are generally bicuspid, delicate, and extremely strong. The tibial and peroneal veins

contain about 7 to 19 valves each. The popliteal vein contains one or two valves and the femoral vein

has generally three. About 70% of common femoral veins have a valve located within 1 cm of the

inguinal ligament. Twenty-five percent of external iliac and 10% of the internal iliac veins have a

valve.125 The common iliac vein generally has no valves. The GSV usually has more than six valves

(range, 4 to 25) with at least one valve within a few centimeters of the SFJ and the SSV has an average

of 7 to 10 valves range, 4 to 13.126 Perforating veins and even larger venules have venous valves.125

Variable numbers of venous lakes (1 to 18 sinuses) are found in the soleus muscle. These sinuses are

valveless, floppy channels linked to small-valved venous channels that prevent reflux to the superficial

system. The sinuses empty into the posterior tibial vein in the proximal calf. Within the gastrocnemius

muscle, there are interlacing valved venous networks that coalesce to form a pair of venous channels

that empty into the popliteal vein. These intramuscular venous chambers store venous blood and are

crucial to calf muscle pump function.

The veins of the abdomen and pelvis begin at the inguinal ligament as the external iliac vein that is

joined medially by the internal iliac to form the common iliac vein. The internal iliac vein drains the

pelvis via connections such as the obturator, gluteal, and internal pudendal veins and their

interconnections. To the right of the fifth lumbar vertebrae and aorta, the common iliac veins join to

form the IVC. Compression of the left iliac vein by the right common iliac artery can lead to a venous

obstructive condition called May-Thurner syndrome. The IVC typically ascends to the right of the aorta

and vertebral column terminating in the right atrium. Its direct tributaries are the lumbar veins, the

right gonadal vein, the renal veins, the right suprarenal vein, the right inferior phrenic vein, and the

hepatic veins. Other named veins generally join one of these tributaries to empty into the IVC. Because

of the embryonic evolutions that lead to the “normal” IVC and its branches, variations are common.

Duplication of the IVC occurs in 0.2% to 0.3% of cases, transposition or a left-sided IVC can occur in

0.2% to 0.5% of cases, and a retroaortic left renal (1.2% to 2.4%), and circumaortic left renal vein

(1.5% to 8.7%) have also been reported.127 In the face of IVC occlusion, veins of the chest and

abdominal wall, the azygos and hemiazygos systems, and vertebral plexuses may play a prominent role

in venous drainage of the lower extremities and abdominal/retroperitoneal cavity.

Normal Venous Physiology

Under conditions of low volume or external pressure, many veins lying within muscle are demonstrated

by duplex scanning to collapse in an elliptical configuration consistent with a thin vein wall and the lack

of in situ external support.128 With muscular relaxation, veins within these compartments change from

an elliptical to a circular configuration to accept venous blood being emptied from the superficial

system and delivered to the lower extremity by arterial inflow. Compliance is very high; in fact,

increasing the venous volume (VV) by over two and one half times results in only a 0- to 15-mm Hg

increment rise in pressure.129 This allows a significant amount of blood (at least 500 mL in the standing

position) to become sequestered in the lower limb without a significant buildup of intraluminal

pressure. However, once a vein reaches its full circular shape, further increases in VV result in a

proportional increase in intraluminal pressure. The capacitance of the venous system has been met and

sustained venous hypertension results in decompensation noted as edema. Normally, modest exercise of

the muscles will expel the contained blood volume present in the veins and reset the capacitance of the

venous system.

In contrast to intramuscular veins, duplex scanning demonstrates that large axial veins (e.g., femoral,

popliteal) collapse in a circular manner. Supported/tethered on all sides by connective tissue, these

veins are subject to equal external pressures along the vein wall and expand or collapse in a direct

response to changes in volume.130 Their compliance mimics that of an artery in that pressure changes

are more reflective of volume changes. They are conduit rather than compliance vessels.

The calf muscle and possibly the thigh muscles act as a pump, the “peripheral heart,” which can

2803

generate pressures of up to 300 mm Hg during exercise.125 Muscle contraction propels the blood toward

the heart and lungs via the cephalad conduit veins. The valves in the proximal superficial and deep veins

open to allow blood to move forward in response to an increased distal pressure gradient. The

perforating vein valves close to prevent venous blood reflux from deep to superficial veins, thereby

preventing high pressures generated in the deep system from affecting superficial structures (i.e., skin,

soft tissues). In addition, blood moves centrally during exercise by compression of the superficial veins

between the deep fascia and skin, but the pressure generated is only 100 to 150 mm Hg.125 As the calf

muscle relaxes, the flow/pressure gradient falls and proximal vein valve closure prevents reflux

(retrograde flow). Arterial blood then slowly fills the venous system; valves in the foot veins and

perforating veins open to allow the deep veins to fill from the superficial system replenishing the calf

muscle pump venous sinuses.

The vein valve functions in a four-phase cycle: opening, equilibrium, closing, and closed phase.

During equilibrium, flow separation occurs at the valve edge, the flow splits into two streams with one

of the streams directed into the valve sinus possibly aiding in a self-cleaning step (preventing stasis).

When maximally open, the two cusps create about a 35% narrowing of the outflow lumen, which may

aid in outflow.131 Interestingly, the majority of the cycle has the valve in the open position. Valve

closure normally occurs within 0.5 to 1.0 second in response to retrograde blood flow and the loss of a

pressure/flow gradient.132,133 Closure time is somewhat dependent on the stimulus to closure and a flow

velocity of at least 30 cm/second is required.134

An IV catheter placed into a foot vein can measure changes in venous pressure over time and with

movement. These measurements reflect normal venous hemodynamics in the distal superficial venous

system.125 When lying flat, a person’s normal lower extremity IV pressure is about 15 mm Hg, but with

standing the pressure rises to reflect the hydrostatic pressure of a column of blood from the heart to the

foot catheter most reflective of the patient’s height (generally ±90 mm Hg). A hemodynamic study of

venous function involves pressure measurements obtained during controlled exercise. The venous filling

time is the time required to arrive at a steady-state pressure after standing. Ten steps (1/second) causes

a drop in pressure, and the lowest pressure, called the ambulatory venous pressure (AVP), is generally

less than 45 mm Hg. The venous refilling time is the time required, following exercise and standing at

rest, to reach the baseline erect pressure. It is normally greater than 20 seconds. This rather simplistic

measurement reflects a complex interaction of the venous conduits, the property of the veins, and the

action of the peripheral pump.135 If one measures the venous pressure in deeper veins and in more

central locations, the measurements would be considerably different, but such measurements are not

commonly obtained in clinical practice.

Prevalence and Impact

3 Chronic venous disease (CVD) is a common, costly malady in Western countries. If one considers the

entire spectrum of the disease, it affects more than 30 million Americans (more than half women).136,137

Varicose veins are observed in 15% to 25% of the adult population.138,139 Chronic venous insufficiency is

defined as venous pathology that results in advanced clinical symptoms (edema to venous ulceration).

Skin changes suggestive of venous disease are noted in 6 to 7 million US citizens, and venous ulcers

occur in up to 2% of those with CVI (approximately 500,000 patients).136,140 Population studies confirm

these earlier clinical observations.141 A population-based study that included Duplex imaging and

utilized a modified CEAP classification (see later) demonstrated that in San Diego, 5.8% of those studied

presented with edema while 6.2% had skin changes and/or prior or active venous ulcers.139 The annual

cost to treat venous ulcers alone is estimated at $1 billion.142,143 It is interesting that similar findings are

noted throughout Europe.144–150 Relevant risk factors for varicose veins are advanced age, a positive

family history, female gender, multiparity, and obesity when based on epidemiologic

studies,136,139,144,145,147,148,151 while the risk factors for CVI are advanced age, positive family history,

and obesity.139,144,148,149

Pathophysiology and Etiology

Three pathophysiologic states exist: obstruction, valvular insufficiency, and calf muscle pump

malfunction. These conditions reflect a failure of one or more of the components of the normal venous

system and are not mutually exclusive.

Venous obstruction causes an increased resistance to blood exiting the lower extremity. There are

current data to suggest that venous occlusive disease in combination with venous insufficiency is found

in 55% of patients with CVI, especially those with the most severe symptoms.152 Clearly in the past,

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