24

Venous and Lymphatic Disease

Atish Chopra, Timothy K. Liem,
chapter and Gregory L. Moneta

Venous Anatomy 981 Risk Factors / 984 Varicose Veins 996

Structure of Veins / 981 Diagnosis / 986 Chronic Venous Insufficiency 997
Lower Extremity Veins / 981 Treatment / 987 Evaluation of Venous Insufficiency / 997
Upper Extremity Veins / 982 Prophylaxis / 992 Lymphedema 1001
Evaluation of the Other Venous Pathophysiology / 1001
Venous System 982 Thrombotic Disorders 994 Clinical Diagnosis / 1001
Clinical Evaluation / 982 Superficial Vein Thrombophlebitis / 994 Radiologic Diagnosis / 1002
Venous Thromboembolism 984 Upper Extremity Vein Thrombosis / 995 Management / 1002
Epidemiology / 984 Mesenteric Vein Thrombosis / 996
Summary 1003

VENOUS ANATOMY Lower Extremity Veins

Veins are part of a dynamic and complex system that returns
low-nutrient deoxygenated blood to the heart. Venous blood
flow is dependent on multiple factors such as gravity, venous
valves, the cardiac and respiratory cycles, blood volume, and the
calf muscle and feet pumps. Alterations in the intricate balance
of these factors can result in venous pathology.
Structure of Veins
Veins are thin-walled, highly distensible, and collapsible. Their
structure specifically supports the primary functions of veins
to transport blood toward the heart and serve as a reservoir to
prevent intravascular volume overload.
The venous intima is composed of a nonthrombogenic
endothelium with an underlying basement membrane and
an elastic lamina. The endothelium produces endothelium-
derived relaxing factors such as nitric oxide and prostacy-
clin, which help maintain a nonthrombogenic surface through
inhibition of platelet aggregation and promotion of platelet
disaggregation.1 The capacitance function of veins is facili-
tated by circumferential rings of elastic tissue, and smooth
muscle located in the media of the vein allows for changes
in vein caliber with minimal changes in venous pressure. The
adventitia is most prominent in large veins and consists of
collagen, elastic fibers, and fibroblasts. When a vein is maxi-
mally distended, its diameter may be several times greater
than that in the supine position.
In the axial veins, unidirectional blood flow is achieved
with multiple venous valves. The inferior vena cava (IVC),
common iliac veins, portal venous system, and cranial sinuses
are valveless. In the axial veins, valves are more numerous
distally in the extremities than proximally. Each valve consists
of two thin cusps of a fine connective tissue skeleton covered by
endothelium. Venous valves close in response to cephalad-to-
caudal blood flow at a velocity of at least 30 cm/s.2
Lower extremity veins are divided into superficial, deep, and
perforating veins. The superficial venous system lies above the
uppermost fascial layer of the leg and thigh and consists of the
great saphenous vein (GSV) and small saphenous vein (SSV)
and their tributaries. The GSV originates from the dorsal pedal
venous arch and courses cephalad and medially, anterior to the
medial malleolus, entering the common femoral vein approxi-
mately 4 cm inferior and lateral to the pubic tubercle. The saphe-
nous nerve accompanies the GSV medially from the ankle to
the level of the knee and supplies cutaneous sensation to the
medial leg and ankle. The SSV originates laterally from the
dorsal pedal venous arch and courses cephalad in the posterior
calf. Most often, it penetrates the popliteal fossa, between the
medial and lateral heads of the gastrocnemius muscle, to join the
popliteal vein. The termination of the SSV may be quite vari-
able, however, with a proximal extension of the SSV (the vein
of Giacomini) connecting with the deep femoral vein or GSV.
The sural nerve accompanies the SSV laterally along its course
and supplies cutaneous sensation to the lateral malleolar region.
The deep veins follow the course of major arteries in the
extremities. In the lower leg, paired veins parallel the course of
the anterior tibial, posterior tibial, and peroneal arteries, to join
behind the knee forming the popliteal vein. Venous bridges con-
nect the paired axial tibial veins in the lower leg. The popliteal
vein continues through the adductor hiatus to become the femo-
ral vein. In the proximal thigh, the femoral vein joins with the
deep femoral vein to form the common femoral vein, becoming
the external iliac vein at the inguinal ligament.
Multiple perforator veins traverse the deep fascia to
connect the superficial and deep venous systems. Potentially
clinically important perforator veins are the posterior tibial and
paratibial perforators (formerly known as the Cockett and Boyd
perforators, respectively). The posterior tibial perforator veins
drain the medial lower leg and are relatively constant. They

http://ebook2book.ir/
 Key Points
1 Thrombolytic therapy, surgical thrombectomy, and place-
ment of inferior vena cava filters are adjunctive treatments
that may be indicated in patients with extensive and compli-
cated venous thromboembolism.
4 High ligation and stripping, endovenous laser, or radiofre-
2 Deep vein thrombosis (DVT) and pulmonary embolism
are well-recognized complications after major abdominal
and orthopedic procedures. The risk is further increased in
patients with malignancy and a history of venous thrombo-
embolism. Options for DVT prophylaxis include intermit-
tent pneumatic compression, use of graduated compression
stockings, and administration of low-dose unfractionated
heparin, low molecular weight heparin, fondaparinux, and
vitamin K antagonists. Direct thrombin inhibitors and factor
5 The mainstay of treatment for chronic venous insufficiency
Xa inhibitors are approved for prophylactic use only for
orthopedic procedures and for recurrent VTE. However,
prophylaxis should be stratified based on the patient’s level
of risk.
6 Lymphedema is categorized as congenital, primary (with
3 In patients with established DVT, unfractionated heparin,
low molecular weight heparin, fondaparinux, and some factor
Xa inhibitors are options for initial antithrombotic therapy.
Vitamin-K antagonists, direct thrombin inhibitors, and factor
Xa inhibitors are utilized for long-term anticoagulation.
connect the posterior accessory GSV (formerly known as the
posterior arch vein, a tributary to the GSV) and the posterior
tibial vein. They may become varicose or incompetent in venous
insufficiency states. The posterior accessory GSV has relevance
as it represents a connection of the three ankle perforating veins,
which are likely of particular importance in the development of
a venous stasis ulcers. The paratibial perforator veins connect
the GSV to the deep veins approximately 10 cm below the knee
and 1 to 2 cm medial to the tibia. Additional perforators in the
thigh are known as the perforators of the femoral canal (also
known as Hunter’s and Dodd’s perforators).
Venous sinuses are thin-walled, large veins located within
the substance of the soleus and gastrocnemius muscles. These
sinuses are valveless and are linked by valved, small venous
channels that prevent reflux. A large amount of blood can be
stored in the venous sinuses before draining into the posterior
tibial and peroneal veins. With each contraction of the calf
muscle bed, blood is pumped out through the venous channels
into the main conduit veins to return to the heart.
Upper Extremity Veins
As in the lower extremity, there are deep and superficial veins in
the upper extremity. Deep digital veins form the palmar venous
arches of the hand and empty into the paired radial and ulnar
veins. These follow the named arteries in the arm and are known
as the venae comitantes. They become the brachial veins most
often near the antecubital fossa and then combine to contrib-
ute to forming the axillary vein. Superficial veins of the upper
extremity are the cephalic and basilic veins and their tributaries.
The cephalic vein originates at the lateral wrist and courses
over the lateral ventral surface of the forearm. In the upper
arm, the cephalic vein terminates in the infraclavicular fossa,
982 piercing the clavipectoral fascia to empty into the axillary vein.
http://ebook2book.ir/
The duration and type of long-term anticoagulation should
be stratified based on the provoked or unprovoked nature of
the DVT, the location of the DVT, previous occurrence of
DVT, and presence of concomitant malignancy.
quency ablation and sclerotherapy are effective therapies for
patients with saphenous vein valvular insufficiency. Con-
comitant varicose veins may be managed with compression
therapy, sclerotherapy, and phlebectomy. New nonthermal
ablative techniques, including the combination of sclero-
therapy with endoluminal mechanical injury as well as injec-
tion of cyanoacrylate, show early promising results.
is compression therapy. Sclerotherapy, perforator vein liga-
tion, and venous reconstruction or ablative techniques may
be indicated in patients in whom conservative management
fails or as a means to decrease ulcer recurrence.
early or delayed onset), or secondary. The goals of treatment
are to minimize edema and prevent infection. Lymphatic
massage, sequential pneumatic compression, use of com-
pression garments, and limb elevation are effective forms of
therapy.
The basilic vein runs medially along the forearm and penetrates
the deep fascia as it courses past the elbow in the upper arm.
It then joins with the deep brachial veins to become the axil-
lary vein, a landmark for identification of the axillary vein. The
median antecubital vein joins the cephalic and the basilic veins
on the ventral surface of the elbow.
The axillary vein becomes the subclavian vein at the lat-
eral border of the first rib. At the medial border of the scalenus
anterior muscle, the subclavian vein joins with the internal jugu-
lar vein to become the brachiocephalic vein, with the subclavian
vein coursing anterior to the scalenus anterior muscle. The left
and right brachiocephalic veins join to become the superior vena
cava, which empties into the right atrium.
EVALUATION OF THE VENOUS SYSTEM
Clinical Evaluation
Evaluation of the venous system begins with a detailed history
and physical examination. Risk factors for acute and chronic
venous disease are identified. They include increased age, his-
tory of venous thromboembolism (VTE), malignancy, trauma
and spinal cord injury, hospitalization and immobilization, obe-
sity, nephrotic syndrome, pregnancy, recent postpartum state,
oral contraceptive use or hormone replacement therapy, vari-
cose veins, and hypercoagulable states, as well as the postopera-
tive state. Venous pathology is often, but not always, associated
with visible or palpable signs that can be identified during the
physical examination. There is variation among individuals in
the prominence of superficial veins when the person is standing
(Fig. 24-1). The superficial veins of a lean athletic person, even
when normal, will appear large and easily visualized, but these
veins will be far less obvious in the obese individual. Signs
of superficial venous abnormalities are listed in Table 24-1.

Figure 24-1. Varicose vein demonstrating evidence of chronic
venous insufficiency.
The deep veins cannot be directly assessed clinically, and
abnormalities within them can only be inferred indirectly from
changes found on clinical examination.
Chronic venous insufficiency (CVI) may lead to character-
istic changes in the skin and subcutaneous tissues in the affected
limb. CVI results from incompetence of venous valves, venous
obstruction, or both. Most CVI involves venous reflux, and
severe CVI often reflects a combination of reflux and venous
obstruction. It is important to remember that although CVI
originates with abnormalities of the veins, the target organ of
CVI is the skin, and the underlying physiologic and biochemical
mechanisms leading to the cutaneous abnormalities associated
with CVI are poorly understood. A typical leg affected by CVI
will be edematous, with edema increasing over the course of the
day. The leg may also be indurated and pigmented with eczema
and dermatitis. These changes are associated with excessive
proteinaceous capillary exudate. Deposition of a pericapil-
lary fibrin cuff may limit nutritional exchange. In addition, an
increase in white blood cell trapping within the skin microcir-
culation in CVI patients may lead to microvascular congestion
and thrombosis. Subsequently, white blood cells may migrate
into the interstitium and release necrotizing lysosomal enzymes,
potentially leading to tissue destruction and eventual ulceration.
Fibrosis can eventually develop from impaired nutrition,
chronic inflammation, and fat necrosis (lipodermatosclerosis).
Hemosiderin deposition due to the extravasation of red cells
and subsequent lysis in the skin contributes to the characteristic
pigmentation of chronic venous disease (Fig. 24-2). Ulceration
can develop with longstanding venous hypertension and is
associated with alterations in microcirculatory and cutaneous
lymphatic anatomy and function. The most common location of
Table 24-1
Possible signs of superficial venous abnormalities
Tortuosity
Varicosity
Venous saccule
Distended subdermal venules (corona phlebectatica)
Distended intradermal venules (spider angiomata)
Warmth, erythema, tenderness (superficial thrombophlebitis)
http://ebook2book.ir/
983
CHAPTER 24 VENOUS AND LYMPHATIC DISEASE
Figure 24-2. Characteristic hyperpigmentation of chronic venous
insufficiency.
venous ulceration is approximately 3 cm proximal to the medial
malleolus, frequently referred to the “gaiter” region (Fig. 24-3).
Trendelenburg’s test is a clinical test, historically impor-
tant but now rarely used, that can help determine whether
incompetent valves are present and in which of the three
venous systems (superficial, deep, or perforator) the valves are
abnormal. There are two components to this test. First, with the
patient supine, the leg is elevated 45° to empty the veins, and
the GSV is occluded with the examiner’s hand or with a rub-
ber tourniquet. Then, with the GSV still occluded, the patient
stands, and the superficial veins are observed for blood filling.
The compression on the GSV is released, and the superficial
veins are observed for filling with blood. A positive result is the
sudden filling of veins with standing while the GSV remains
occluded, indicating incompetent perforator and deep veins.
Additionally, the GSV valves are incompetent if rapid filling
is noted following release of compression. A negative result,
indicating no clinically relevant venous reflux, is the gradual
filling of the veins from arterial inflow. Interpretation of the
findings of Trendelenburg’s test is subjective, and therefore, it
has largely been supplanted by the more objective noninvasive
vascular laboratory tests to localize sites of venous reflux.
Noninvasive Evaluation. Before the development of vascu-
lar ultrasound, noninvasive techniques to evaluate the venous
system were based on plethysmographic techniques. Although
a variety of plethysmographic techniques are used in the
984
PART II
SPECIFIC CONSIDERATIONS
Figure 24-3. Venous ulceration located proximal to the medial
malleolus.
evaluation of both acute and chronic venous disease, they are
all based on the detection of volume changes in the limb in
response to blood flow.
Duplex ultrasonography (DUS) augmented by color
flow imaging is now the most important noninvasive diagnos-
tic method in the evaluation of the venous system. DUS has
become standard for the detection of infrainguinal deep vein
thrombosis (DVT), with near 100% sensitivity and specificity in
symptomatic patients.3 It is also the preferred method of evalu-
ation for upper extremity venous thrombosis and is useful in
the evaluation of CVI by documenting the presence of valvular
reflux and venous obstruction. Overlying bowel gas and large
body habitus many times make DUS less applicable to evalu-
ation of intra-abdominal veins. Magnetic resonance venogra-
phy (MRV) and computed tomography (CT) venography are
alternative noninvasive techniques for evaluation of pelvic and
intra-abdominal veins.
Invasive Evaluation. Improved accuracy of noninvasive
techniques for diagnostic purposes has made the use of invasive
procedures more selective. Both venography and intravascular
ultrasound (IVUS) are used as adjuncts to percutaneous or open
surgical treatment of venous disorders. When planning endo-
vascular or open surgical treatment, venography may be used to
identify areas of obstruction in infrainguinal, intra-abdominal,
and upper extremity veins as well as reflux in intra-abdominal
and infrainguinal veins. IVUS, with access generally via the
common femoral vein, is used primarily to assess for occlusive
lesions of the iliac veins and appears more sensitive than venog-
raphy in detecting iliac vein obstruction.4
http://ebook2book.ir/
Complications of venography include pain, thrombosis,
or hematoma at the puncture site. Pain is lower with nonionic
low-osmolality contrast media than with conventional contrast
agents (with 18% vs. 44% of patients experiencing discomfort,
respectively).5 Systemic effects of iodinated contrast media
include allergic reaction and risk of renal failure. Postvenogra-
phy venous thrombosis occurs distal to the venous puncture site
in 1% to 9% of patients undergoing venography secondary to
intimal damage from the intravenous (IV) contrast agent.5 Com-
plications and limitations of IVUS are related to complications
at the access site and cost of the catheters.
VENOUS THROMBOEMBOLISM
Epidemiology
Despite increased awareness and use of prophylactic modalities,
DVT or pulmonary embolism (PE), venous thromboembolism
(VTE), remain important preventable sources of morbidity and
mortality, especially in the surgical patient. The incidence of
VTE is approximately 100 per 100,000 people per year in the
general population, with 20% of the diagnoses made within
3 months of a surgical procedure. Of the symptomatic patients,
one-third will present with PE and two-thirds with DVT.6,7 The
estimated number of cases of VTE may well be over 600,000
per year in the United States, making it a major U.S. health
problem.8 Furthermore, death occurs in 6% of DVT and 12% of
PE cases within 1 month of diagnosis, although not all deaths
are directly secondary to VTE, with many related to the under-
lying problem leading to the VTE event.6 However, not only
does VTE pose a veritable threat to life, it also places patients at
higher risk for recurrence and post-VTE sequelae such as pul-
monary hypertension and postthrombotic syndrome, with 4%
and up to 30% incidence, respectively.9-11
Risk Factors
Three broadly stated conditions, first described by Rudolf Vir-
chow in 1862, contribute to VTE formation: stasis of blood
flow, endothelial damage, and hypercoagulability. Of these
risk factors, relative hypercoagulability appears most impor-
tant in cases of spontaneous VTE, or so-called idiopathic VTE,
whereas stasis and endothelial damage likely play a greater
role in secondary VTE, or so-called provoked VTE, occurring
in association with transient risk factors such as immobiliza-
tion, surgical procedures, and trauma. Identifiable risk factors
for VTE generally relate to one of the conditions described by
Virchow. Often more than one risk factor is present contribut-
ing in an exponential, rather than additive, manner. Specific
risk factors for VTE are listed in Table 24-2.
The more common acquired VTE risk factors include
older age (>40 years), hospitalization and immobilization, hor-
mone replacement and oral contraceptive therapy, pregnancy
and the recently postpartum state, prior VTE, malignancy, major
surgery, obesity, nephrotic syndrome, trauma and spinal cord
injury, long-haul travel (>6 hours), varicose veins, antiphospho-
lipid syndrome, myeloproliferative disorders, and polycythemia.
Heritable risk factors include male sex, factor V Leiden muta-
tion; prothrombin 20210A gene variant; antithrombin, protein
C, and protein S deficiencies; and dysfibrinogenemias. In some
patients, the cause of the thrombophilia may have both a heri-
table and an acquired component. These mixed causes include
homocysteinemia; factors VII, VIII, IX, and XI elevation;
hyperfibrinogenemia; and activated protein C resistance in the
Table 24-2
absence of factor V Leiden.12 There may be a synergistic effect 985
when particular multiple inherited and acquired risk factors are
Risk factors for venous thromboembolism present in the same patient.
Acquired Other patient-specific factors associated with venous
Advanced age thrombosis include the traditional cardiovascular risk factors
Hospitalization/immobilization of obesity, hypertension, and diabetes. VTE is more common
Hormone replacement therapy and oral contraceptive use in whites and African Americans than Asians and Native
Pregnancy and puerperium Americans.13,14 Certain gene variants (single nucleotide
polymorphisms) are also associated with a mildly increased risk
Prior venous thromboembolism
for VTE, and their presence may interact with other risk factors
Malignancy

CHAPTER 24 VENOUS AND LYMPHATIC DISEASE

to increase the overall risk for venous thrombosis.15
Major surgery Anatomic factors may also contribute to development
Obesity of DVT. At the site where the right iliac artery crosses over
Nephrotic syndrome the left iliac vein, the left iliac vein may become chronically
Trauma or spinal cord injury compressed predisposing to iliofemoral venous thrombosis,
Long-haul travel (>6 hours) so-called May-Thurner syndrome. External compression of
Varicose veins major veins by masses of various types can also lead to venous
Antiphospholipid antibody syndrome thrombosis.
Myeloproliferative disease Many cases of VTE are potentially preventable. Accord-
Polycythemia ingly, in current clinical practice, preoperative VTE risk assess-
ment is becoming increasingly common to identify patients at
Inherited moderate and high risk. Scoring systems have been developed
Factor V Leiden that take into account the number of VTE risk factors in an
Prothrombin 20210A individual patient. These risk stratification scores, such as the
Antithrombin deficiency Rogers score16 and Caprini score,17 provide individual patient
Protein C deficiency risk stratification and recommendations for prophylactic anti-
Protein S deficiency coagulation. The ninth edition of the American College of
Factor XI elevation Chest Physicians (ACCP) Guidelines for Prevention of VTE
Dysfibrinogenemia in Non-Orthopedic Surgical Patients acknowledges both the
Rogers and Caprini scores and provides recommendations for
Mixed Etiology
VTE prophylaxis (Table 24-3). Orthopedic surgical patients
Homocysteinemia
are generally excluded from risk assessment scores because
Factors VII, VIII, IX, XI elevation of the disproportionately increased risk of VTE in orthopedic
Hyperfibrinogenemia surgery compared with the general and abdominopelvic
Activated protein C resistance without factor V Leiden surgery population.

Table 24-3
Thromboembolism risk and recommended thromboprophylaxis in surgical patients
APPROXIMATE DVT RISK WITHOUT SUGGESTED THROMBOPROPHYLAXIS
LEVEL OF RISK THROMBOPROPHYLAXIS (%) OPTIONS
Very low risk <0.5% (Rogers score <7; No specific thromboprophylaxis
General or abdominopelvic surgery Caprini score 0) Early ambulation
Low risk ∼1.5% (Rogers score 7–10; Mechanical prophylaxis
General or abdominopelvic surgery Caprini score 1–2)
Moderate risk ∼3.0% (Rogers score >10; LMWH (at recommended doses),
General or abdominopelvic surgery Caprini score 3–4) LDUH, or mechanical prophylaxis
High bleeding risk Mechanical prophylaxis
High risk ∼6% (Caprini score ≥5) LMWH (at recommended doses),
General or abdominopelvic surgery fondaparinux and mechanical prophylaxis
High bleeding risk Mechanical thromboprophylaxis
General or abdominopelvic surgery Extended-duration LMWH (4 weeks)
for cancer
DVT = deep vein thrombosis; INR = international normalized ratio; LDUH = low-dose unfractionated heparin; LMWH = low molecular weight heparin;
VTE = venous thromboembolism.
Data from Gould MK, Garcia DA, Wren SM, et al: Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of
Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines, Chest. 2012 Feb;141(2 Suppl):e227S-e277S.

http://ebook2book.ir/
986 Diagnosis
Clinical Evaluation. Early in the course of DVT development,
venous thrombosis is thought to begin in an area of relative stasis,
such as a soleal sinus vein or immediately downstream of the
cusps of a venous valve in an axial calf vein. Isolated proxi-
mal DVT without tibial vein thrombosis is unusual. Early in the
course of a DVT, there may be no or few clinical findings such
as pain or swelling. Even extensive DVT may sometimes be
present without signs or symptoms if the patient is nonambula-
tory or bedbound. History and physical examination are notori-
ously unreliable in the diagnosis of DVT. In addition, symptoms
PART II
and signs often associated with DVT, such as extremity pain
and/or swelling, are nonspecific. In large studies, DVT has been
found by venography or DUS in ≤50% of patients in whom it
was clinically suspected.18,19 Objective studies are therefore
required to confirm a diagnosis of VTE or to exclude the pres-
SPECIFIC CONSIDERATIONS
ence of VTE.
Clinical symptoms may worsen as DVT propagates and
involves the major proximal deep veins. Extensive DVT of the
major axial deep venous channels of the lower extremity with rel-
ative sparing of collateral veins causes a condition called phleg-
masia cerulea dolens (Fig. 24-4). This condition is characterized
by pain and pitting edema with associated cyanosis. When the
thrombosis extends to the collateral veins, massive fluid seques-
tration and more significant edema ensue, resulting in a condition
known as phlegmasia alba dolens.20 The affected extremity in
phlegmasia alba dolens is extremely painful and edematous and
pale secondary to arterial insufficiency from dramatically ele-
vated below lower knee compartment pressures. Both phlegmasia
cerulean dolens and phlegmasia alba dolens can be complicated
by venous gangrene and the need for amputation.
Vascular Lab and Radiologic Evaluation
Duplex Ultrasound DUS is now the most commonly per-
formed test for the detection of infrainguinal DVT, both above
and below the knee, and has a sensitivity and specificity of
>95% in symptomatic patients.3 DUS refers to the combina-
tion of real-time B-mode ultrasound with compression and flow
augmentation amneuvres combined with pulsed Doppler capa-
bility. For VTE detection, color flow imaging is an additional
extremely useful adjunct in the evaluation of possible axial
calf vein DVT and evaluation of intra-abdominal veins. DUS
provides the ability to noninvasively visualize venous anatomy,
detect occluded and partially occluded venous segments, and
demonstrate physiologic flow characteristics.
In the supine patient, normal lower extremity venous flow
is phasic (Fig. 24-5), decreasing with inspiration in response
Figure 24-4. Phlegmasia cerulea dolens of the left leg. Note the
bluish discoloration.
http://ebook2book.ir/
Figure 24-5. Duplex ultrasound scan of a normal femoral vein
with phasic flow signals.
to increased intra-abdominal pressure with the descent of the
diaphragm and then increasing with expiration as the diaphragm
rises and intra-abdominal pressure decreases. When the patient
is upright, the decrease in intra-abdominal pressure with expira-
tion cannot overcome the hydrostatic column of pressure exist-
ing between the right atrium and the calf. Muscular contractions
of the calf, along with the one-way venous valves, are then
required to promote venous return to the heart. Flow also can be
increased by leg elevation or compression and decreased by sud-
den elevation of intra-abdominal pressure (Valsalva maneuver).
In a venous DUS examination performed with the patient
supine, spontaneous flow, variation of flow with respiration, and
response of flow to Valsalva maneuver are all assessed. From
the common femoral through the popliteal vein, the primary
method of detecting DVT with ultrasound is demonstration of
the lack of compressibility of the vein with probe pressure on
B-mode imaging. Normally, in transverse section, the vein walls
should coapt with pressure. Lack of coaptation indicates throm-
bus. Axial calf vein thrombi are often best detected by abnor-
malities in color flow imaging as compressibility is difficult in
the calf.
The examination begins at the ankle and continues proxi-
mally to the groin. Each vein is visualized, and the flow signal is
assessed with distal and proximal compression. Lower extremity
DVT can be diagnosed by any of the following DUS findings:
lack of spontaneous flow (Fig. 24-6), inability to compress the
vein (Fig. 24-7), absence of color filling of the lumen by color
flow DUS, loss of respiratory flow variation, and venous disten-
tion. Again, lack of venous compression on B-mode imaging
is the primary diagnostic variable. Several studies comparing
B-mode ultrasound to venography for the detection of femo-
ropopliteal DVT in patients clinically suspected to have DVT
report sensitivities of >91% and specificities of >97%.21,22 The
ability of DUS to assess isolated calf vein DVT varies greatly,
with sensitivities ranging from 50% to 93% and specificities
approaching 100%.23,24
Impedance Plethysmography Impedance plethysmography
(IPG) was the primary noninvasive method of diagnosing DVT
before the widespread use of DUS but is infrequently used today.
Changes in electrical resistance resulting from lower extremity
blood volume changes are quantified. IPG is less accurate than
DUS for the detection of proximal DVT, with 83% sensitivity
in symptomatic patients. It is a poor detector of calf vein DVT.25

Figure 24-6. Duplex ultrasound of a femoral vein containing
thrombus demonstrating no flow within the femoral vein.
Iodine-125 Fibrinogen Uptake Iodine-125 fibrinogen uptake
(FUT) is a seldom-used technique that involves IV administra-
tion of radioactive fibrinogen and monitoring for increased
uptake in fibrin clots. An increase of 20% or more in one area
of a limb indicates an area of thrombus. FUT can detect DVT
in the calf, but high background radiation from the pelvis and
the urinary tract limits its ability to detect proximal DVT. It
also cannot be used in an extremity that has recently undergone
surgery or has active inflammation. In a prospective study, FUT
had a sensitivity of 73% and specificity of 71% for identification
of DVT in a group of symptomatic and asymptomatic patients.26
Currently, FUT is primarily a research tool of historic interest.
Venography Venography is the gold standard to which other
diagnostic modalities are compared. A small catheter is placed
in a dorsal foot vein with injection of a radiopaque contrast
agent. Radiographs are obtained in at least two projections.
A positive study result is failure to fill the deep system with
passage of the contrast medium into the superficial system or
demonstration of discrete filling defects (Fig. 24-8). A normal
study result virtually excludes the presence of DVT. In a study
of 160 patients with a normal venogram followed for 3 months,
R FVP R FVP
No compression Compression
Figure 24-7. B-mode ultrasound of the femoral vein in cross-
section. The femoral vein does not collapse with external compres-
sion (arrows).
http://ebook2book.ir/
987
CHAPTER 24 VENOUS AND LYMPHATIC DISEASE
Figure 24-8. Venogram showing a filling defect in the popliteal
vein (arrows).
only two patients (1.3%) subsequently developed DVT, and
no patients experienced symptoms of PE.27 Venography is not
routinely used in clinical practice because of its invasiveness
and complication risk. It is still, however, sometimes used in
research studies evaluating DVT prophylaxis.
Treatment
Once the diagnosis of VTE has been made, antithrombotic ther-
apy should be initiated promptly. If clinical suspicion for VTE is
high, it may be prudent to start treatment before the diagnosis is
objectively confirmed. The goals of VTE treatment are the pre-
vention of mortality and morbidity associated with PE and the
prevention of the postthrombotic syndrome (PTS). Treatment
1 regimens may include antithrombotic therapy, temporary or
permanent vena cava filter placement, catheter-directed or
systemic thrombolytic therapy, and operative thrombectomy.
Antithrombotic Therapy. Most often, antithrombotic therapy
for VTE is initiated with IV or subcutaneous (SC) unfraction-
ated heparin or SC low molecular weight heparin. Fondaparinux,
a synthetic pentasaccharide, is sometimes also used as an alter-
native to heparin to initiate therapy. An oral vitamin K antago-
nist, usually sodium warfarin, is begun shortly after initiation of
IV or SC therapy. Either SC or IV therapy is continued until
effective oral anticoagulation with warfarin is achieved as indi-
cated by an international normalized ratio (INR) ≥2 for 24 hours.
A minimum of 5 days of heparin or fondaparinux therapy is
988 recommended.28 Recently, several oral anticoagulants that
2 function by either directly inhibiting thrombin or inhibit-
ing factor Xa have additionally been approved by the
United States Food and Drug Administration (FDA) for both
treatment and prophylaxis for VTE. A principle advantage is
they do not require monitoring of laboratory parameters for use.
Unfractionated heparin (UFH) binds to antithrombin via
a specific 18-saccharide sequence. This increases antithrombin
activity over a thousandfold. The antithrombin-heparin complex
primarily inhibits factor IIa (thrombin) and factor Xa and, to
a lesser degree, factors IXa, XIa, and XIIa of the coagulation
cascade. In addition, UFH also binds to tissue factor pathway
PART II
inhibitor, which inhibits the conversion of factors X to Xa,
and factors IX to IXa. Finally, UFH catalyzes the inhibition of
thrombin by heparin cofactor II via a mechanism independent
of antithrombin.
UFH therapy is most commonly administered with an
SPECIFIC CONSIDERATIONS
initial IV bolus of 80 units/kg. Weight-based UFH dosages have
been shown to be more effective than standard fixed boluses
in rapidly achieving therapeutic levels.29 The initial bolus is
followed by a continuous IV drip at 18 units/kg per hour. The
half-life of IV UFH ranges from 45 to 90 minutes and is dose
dependent. The level of antithrombotic therapy should be moni-
tored every 6 hours using the activated partial thromboplastin
time (aPTT), with the goal range of 1.5 to 2.5 times control
values. This should correspond with plasma heparin anti-Xa
activity levels of 0.3 to 0.7 IU/mL.
Initial anticoagulation with UFH may also be administered
SC, although this route is less commonly used. Adjusted-dose
therapeutic SC UFH is initiated with 17,500 units, followed
by 250 units/kg twice daily, and dosing is adjusted to an aPTT
goal range similar to that for IV UFH. Fixed-dose unmonitored
SC UFH is started with a bolus of 333 units/kg, followed by
250 units/kg twice daily.30
Hemorrhage is the primary complication of UFH therapy.
The rate of major hemorrhage (fatal, intracranial, retroperitoneal,
or requiring transfusion of >2 units of packed red blood cells)
is approximately 5% in hospitalized patients undergoing UFH
therapy (1% in medical patients and 8% in surgical patients).30
For patients with UFH-related bleeding complications, cessation
of UFH is required, and anticoagulation may be reversed with
protamine sulfate. Protamine sulfate binds to UFH and forms an
inactive salt compound. Each milligram of protamine neutral-
izes 90 to 115 units of heparin, and the dosage should not exceed
50 mg IV over any 10-minute period. Side effects of protamine
sulfate include hypotension, pulmonary edema, and anaphylaxis.
Patients with prior exposure to protamine-containing insulin
(NPH) and patients with allergy to fish may have an increased
risk of hypersensitivity, although no direct relationship has been
established. Protamine administration should be performed judi-
ciously and terminated if any side effects occur.
In addition to hemorrhage, heparin also has other, unique,
complications. Heparin-induced thrombocytopenia (HIT)
results from heparin-associated antiplatelet antibodies (HAAbs)
directed against platelet factor 4 complexed with heparin. 31
HIT occurs in 1% to 5% of patients treated with heparin.32,33 In
patients with repeat heparin exposure (such as vascular surgery
patients), the incidence of HAAbs may be as high as 21%.34 HIT
occurs most frequently in the second week of therapy and may
lead to disastrous venous or arterial thrombotic complications.
Therefore, platelet counts should be monitored periodically in
patients receiving continuous heparin therapy.
http://ebook2book.ir/
HIT is diagnosed based on previous exposure to heparin,
platelet count less than 100,000, and/or platelet count decline of
50% following exposure. All heparin must be stopped and alter-
native anticoagulation initiated immediately to avoid thrombotic
complications, which may approach 50% over the subsequent
30 days in affected individuals.35
Another complication of prolonged high-dose heparin
therapy is osteopenia. Heparin-induced osteopenia results from
impairment of bone formation and enhancement of bone resorp-
tion by heparin.
Low molecular weight heparins (LMWHs) are derived
from the depolymerization of porcine UFH. Like UFH,
LMWHs bind to antithrombin via a specific pentasaccharide
sequence to expose an active site for the neutralization of fac-
tor Xa. However, LMWHs have fewer additional saccharide
units. This results in less inactivation of thrombin (factor IIa).
In comparison to UFH, LMWHs have increased bioavailability
(>90% after SC injection), longer half-lives (approximately 4 to
6 hours), and more predictable elimination rates.
Most patients treated with weight-based once- or twice-
daily SC LMWH injections do not require laboratory monitoring
for anticoagulant effect, a distinct advantage over continuous IV
infusions of UFH. Patients who do require monitoring include
those with significant renal insufficiency, pediatric patients,
obese patients greater than 120 kg, and pregnant patients. Moni-
toring may be performed using anti-Xa activity assays. The ther-
apeutic anti-Xa goal range depends on the type of LMWH and
the frequency of dosing. There are numerous LMWHs avail-
able, and the various preparations differ in their anti-Xa and
anti-IIa activities. Treatment dosing for one LMWH, therefore,
cannot be extrapolated for use with another. The anticoagulant
effect of LMWHs may be partially reversed (approximately
60%) with protamine sulfate.
Numerous well-designed trials comparing SC LMWH
with IV and SC UFH for the treatment of DVT have been
critically evaluated in several meta-analyses and demonstrate a
decrease in thrombotic complications, bleeding, and mortality
with LMWHs.36-38 LMWHs also are associated with a decreased
rate of HAAb formation and HIT (<2%) compared with UFH
(at least in prophylactic doses).30 However, patients with estab-
lished HIT also should not receive LMWHs because there is
cross-reactivity between the drugs.39
A major benefit of LMWHs is that it allows outpatient
treatment of VTE.40,41 In a randomized study comparing IV
UFH and the LMWH nadroparin calcium,40 there was no sig-
nificant difference in recurrent thromboembolism (8.6% for
UFH vs. 6.9% for LMWH) or major bleeding complications
(2.0% for UFH vs. 0.5% for LMWH). There was, however,
a 67% reduction in mean days in the hospital for the LMWH
group.
Fondaparinux currently is a synthetic pentasaccharide that
has been approved by the FDA for the initial treatment of DVT
and PE. Its five-polysaccharide sequence binds and activates
antithrombin, causing specific inhibition of factor Xa. In two
large noninferiority trials, fondaparinux was compared with the
LMWH enoxaparin for the initial treatment of DVT and with IV
UFH for the initial treatment of PE.42,43 The rates of recurrent
VTE ranged from 3.8% to 5%, with rates of major bleeding of
2% to 2.6%, for all treatment arms. The drug is administered SC
once daily with a weight-based dosing protocol: 5 mg, 7.5 mg,
or 10 mg for patients weighing <50 kg, 50 to 100 kg, or >100 kg,
respectively. The half-life of fondaparinux is approximately
17 hours in patients with normal renal function. There are rare
case reports of fondaparinux-induced thrombocytopenia.44
Direct thrombin inhibitors (DTIs) include parental forms
with recombinant hirudin, argatroban, and bivalirudin, as well
as an oral agent, dabigatran. These antithrombotic agents bind
to thrombin, inhibiting the conversion of fibrinogen to fibrin
as well as thrombin-induced platelet activation. These actions
are independent of antithrombin. The parental DTIs should be
reserved for (a) patients in whom there is a high clinical suspi-
cion or confirmation of HIT, and (b) patients who have a his-
tory of HIT or test positive for heparin-associated antibodies
whereas dabigatran can be used as an alternative to Warfarin
when INR monitoring is difficult or impractical. In patients with
established HIT, DTIs should be administered for at least 7 days,
or until the platelet count normalizes. Warfarin may then be
introduced slowly, overlapping therapy with a DTI for at least
5 days, or dabigatran may be continued instead of Warfarin.45
Bivalirudin is approved primarily for patients with or
without HIT who undergo percutaneous coronary intervention
and is rarely used outside of that setting.
Argatroban is indicated for the prophylaxis and treatment
of thrombosis in HIT. It also is approved for patients with, or at
risk for, HIT undergoing percutaneous coronary intervention.
Antithrombotic prophylaxis and therapy are initiated with a con-
tinuous IV infusion of 2 µg/kg per minute, without the need for a
bolus. The half-life ranges from 39 to 51 minutes, and the dosage
is adjusted to maintain an aPTT of 1.5 to 3 times normal. Large ini-
tial boluses and higher rates of continuous infusion are reserved for
patients with coronary artery thrombosis and myocardial infarc-
tion. In these patients, therapy is monitored using the activated
clotting time. Argatroban is metabolized and excreted by the liver;
therefore, dosage adjustments are needed in patients with hepatic
impairment. There is no reversal agent for argatroban.
The oral agent, dabigatran, is US FDA-approved since
2014 for the treatment of VTE and prophylaxis for recurrent
VTE. Additionally, limited approval was obtained in 2015 for
prophylaxis of VTE after hip replacement surgery. It is admin-
istered as a prodrug, dabigatran etexilate, that is converted to
the active form, dabigatran, in the liver. The half-life ranges
from 12 to 17 hours; it is therefore administered once daily for
prophylaxis and twice daily for VTE therapy. Absorption is not
dietary dependent, and no drug level monitoring is required.
Dabigatran is metabolized in the kidney, and dose adjustment
is required for renal insufficiency. Data on use in obese patients
is limited; therefore, use is not recommended for patients with
a body mass index ≥40 kg/m2 or ≥120 kg.46 Dyspepsia is a com-
mon side effect that may limit use in some patients.47 Dabigatran
may be reversed with idarucizumab in emergent situations.48 It
is contraindicated in patients with mechanical heart valves.
Direct factor Xa inhibitors, which are comprised of the
oral agents rivaroxaban, apixiban, and edoxaban, are FDA
approved for treatment in VTE and prophylaxis for recurrent
VTE. Additionally, rivaroxoban and apixiban are approved by
the FDA for VTE prophylaxis following knee and hip replace-
ment surgery. These medications function by inactivating cir-
culating and thrombus-bound factor Xa. They are metabolized
in the kidney (25–35%) and in the liver; therefore, use is not rec-
ommended in patients with renal insufficiency (creatinine clear-
ance <30 mL/min for rivaroxaban, or <15 mL/min for apixiban
and edoxaban) or severe hepatic insufficiency. As with the oral
DTI, dabigatran, data on use in obese patients is limited; there-
fore, use is not recommended in these patients. Additionally,
http://ebook2book.ir/
these agents are contraindicated in pregnancy. There are no 989
specific reversal agents available for direct factor Xa inhibi-
tors. For severe cases of hemorrhage, indirect partial reversal
may be achieved with use of prothrombin complex concentrate
administration.49
Rixaroxaban has a half-life of 7 to 17 hours. Therapy does
not require monitoring. Prophylactic dosing is 10 mg once daily,
and therapeutic dosing is 15 mg twice daily for 21 days, fol-
lowed by 20 mg once daily thereafter.
Apixiban has a half-life of 5 to 9 hours. Therapy does
CHAPTER 24 VENOUS AND LYMPHATIC DISEASE
not require monitoring, and there are no dietary restrictions. If
monitoring is desired in situations of bleeding or concern for
sub- or supratherapeutic dosing, serum anti-Xa levels can be
obtained. Prophylactic dosing is 2.5 mg twice daily, and thera-
peutic dosing is 10 mg daily for 7 days, followed by 5 mg twice
daily thereafter.
Edoxaban has a half-life of 10 to 14 hours. Therapy does
not require monitoring. Typical dosing is 60 mg once daily,
and 30 mg once daily if creatinine clearance ranges from 15 to
50 mL/min, or body weight ≤60 kg.
Vitamin K antagonists, which include warfarin and other
coumarin derivatives, are the traditional mainstay of long-term
antithrombotic therapy in patients with VTE. Warfarin inhib-
its the γ-carboxylation of vitamin K–dependent procoagulants
(factors II, VII, IX, and X) and anticoagulants (proteins C and S),
resulting in formation of less functional proteins. Warfarin usu-
ally requires several days to achieve full effect because normal
circulating coagulation proteins must first undergo their normal
degradation. Factors X and II have the longest half-lives, in the
range of 36 and 72 hours, respectively. A steady-state concen-
tration of warfarin is usually not reached for 4 to 5 days.
Warfarin therapy is monitored by measuring the INR,
calculated using the following equation:
INR = (patient prothrombin time/laboratory
normal prothrombin time)ISI
where ISI is the international sensitivity index. The ISI describes
the strength of the thromboplastin that is added to activate the
extrinsic coagulation pathway. The therapeutic target INR range
is usually 2.0 to 3.0, but the response to warfarin is variable and
depends on liver function, diet, age, and concomitant medica-
tions. In patients receiving anticoagulation therapy without con-
comitant thrombolysis or venous thrombectomy, the vitamin K
antagonist may be started on the same day as the initial paren-
teral anticoagulant, usually at doses ranging from 5 to 10 mg.
Smaller initial doses may be needed in older and malnourished
patients, in those with liver disease or congestive heart failure,
and in those who have recently undergone major surgery.49
The recommended duration of warfarin antithrombotic
therapy is stratified based on whether the DVT was provoked or
unprovoked, whether it was the first or a recurrent episode, where
the DVT is located, and whether malignancy or thrombophilia is
3 present. Current ACCP recommendations for duration of
warfarin therapy are summarized in Table 24-4.
In patients with proximal DVT, several randomized clini-
cal trials have demonstrated that shorter-term antithrombotic
therapy (4 to 6 weeks) is associated with a higher rate of VTE
recurrence than 3 to 6 months of anticoagulation.50-52 In these
trials, most of the patients with transient risk factors had a low
rate of recurrent VTE, and most recurrences were in patients
with continuing risk factors. The ACCP recommendation, there-
fore, is that 3 months of anticoagulation are sufficient to prevent
990 Table 24-4
bleeding, warfarin anticoagulation may be reversed by (a) omit-
ting or decreasing subsequent dosages, (b) administering oral or
Summary of American College of Chest Physicians parenteral vitamin K, or (c) administering fresh frozen plasma,
recommendations regarding duration of long-term prothrombin complex concentrate, or recombinant factor VIIa.49
antithrombotic therapy for deep vein thrombosis (DVT) Warfarin therapy rarely may be associated with the devel-
opment of skin necrosis and limb gangrene. These conditions
ANTITHROMBOTIC TREATMENT occur more commonly in women (4:1), and the most commonly
CLINICAL SUBGROUP DURATION affected areas are the breast, buttocks, and thighs. This com-
First episode DVT/transient VKA or LMWH for 3 months plication, which usually occurs in the first days of therapy, is
risk/surgery occasionally, but not exclusively, associated with protein C or
S deficiency and malignancy. Patients who require continued
First episode DVT/ VKA or LMWH for 3 months
anticoagulation may restart low-dose warfarin (2 mg) while
PART II

unprovoked Consider for long-term

receiving concomitant therapeutic heparin. The warfarin dosage
therapy if:
is then gradually increased over a 1- to 2-week period.49
r
1SPYJNBM
%75
r
.JOJNBM
CMFFEJOH
SJTL Systemic and Catheter-Directed Thrombolysis. Patients
r
4UBCMF
DPBHVMBUJPO
with extensive proximal, iliofemoral DVT may benefit from
SPECIFIC CONSIDERATIONS

monitoring systemic thrombolysis or catheter-directed thrombolysis (CDT).

Distal DVT/unprovoked
r
4ZNQUPNBUJD VKA for 3 months
r
"TZNQUPNBUJD
BOE
Serial imaging in 2 weeks,
no risk factors for if progression VKA for
progression 3 months
Second episode DVT/ VKA for extended therapy
unprovoked
DVT and cancer LMWH for extended therapy
over VKA
LMWH = low molecular weight heparin; VKA = vitamin K antagonist.
Data from Kearon C, Akl EA, Comerota AJ, et al: Antithrombotic
therapy for VTE disease: Antithrombotic Therapy and Prevention of
Thrombosis, 9th ed: American College of Chest Physicians Evidence-
Based Clinical Practice Guidelines, Chest. 2012 Feb;141(2 Suppl):
e419S-e496S.
recurrent VTE in patients with DVT occurring around the time
of a transient risk factor (e.g., hospitalization or orthopedic or
major general surgery).
In contrast to patients with thrombosis related to transient
risk factors, patients with unprovoked VTE are much more likely
to develop recurrence (rates as high as 40% at 10 years). In this
latter group of patients, numerous clinical trials have compared
3 to 6 months of anticoagulation therapy with extended-duration
warfarin therapy, both at low intensity (INR of 1.5 to 2.0) and at
conventional intensity (INR of 2.0 to 3.0).53-55 In patients with
idiopathic DVT, extended-duration antithrombotic therapy is
associated with a relative reduction in the rate of recurrent VTE
by 75% to >90%. In addition, conventional-intensity warfarin
reduces the risk even further compared with low-intensity war-
farin (0.7 events per 100 person-years vs. 1.9 events per 100
person-years) without an increase in bleeding complications.56
In patients with VTE in association with a hypercoagulable
condition, the optimal duration of anticoagulation therapy is influ-
enced more by the clinical circumstances at the time of the VTE
(idiopathic vs. secondary) than by the actual presence or absence
of the more common thrombophilic conditions. In patients with
VTE related to malignancy, increasing evidence suggests that
longer-term therapy with LMWH (up to 6 months) is associated
with a lower VTE recurrence than treatment using conventional
vitamin K antagonists.57,58 The primary complication of warfarin
therapy is hemorrhage, and the risk is related to the magnitude
of INR prolongation. Depending on the INR and the presence of
CDT appears to be more effective (see later in chapter) and
potentially reduces acute congestive lower extremity symp-
toms more rapidly than anticoagulation alone and decreases the
development of PTS.
Several thrombolytic agents are available, including strep-
tokinase, urokinase, alteplase (recombinant tissue plasminogen
activator), reteplase, and tenecteplase. All share the ability to con-
vert plasminogen to plasmin, which leads to the degradation of
fibrin. They differ with regard to their half-lives, their potential
for inducing fibrinogenolysis (generalized lytic state), their poten-
tial for antigenicity, and their FDA-approved indications for use.
Streptokinase is purified from β-hemolytic Streptococcus
and is approved for the treatment of acute myocardial infarction,
PE, DVT, arterial thromboembolism, and occluded central lines
and arteriovenous shunts. It is not specific for fibrin-bound plas-
minogen, however, and its use is limited by its significant rates of
antigenicity. Fevers and shivering occur in 1% to 4% of patients.
Urokinase is derived from human neonatal kidney cells
grown in tissue culture. Currently, it is only approved for lysis
of massive PE or PE associated with unstable hemodynamics.
Alteplase, reteplase, and tenecteplase all are recombinant
variants of tissue plasminogen activator. Alteplase is indicated
for the treatment of acute myocardial infarction, acute ischemic
stroke, and acute massive PE. However, it often is used for CDT
of DVT. Reteplase and tenecteplase are indicated only for the
treatment of acute myocardial infarction.
Systemic thrombolysis was evaluated in numerous older
prospective and randomized clinical trials, and its efficacy
was summarized in a recent Cochrane Review.59 In 12 studies
involving over 700 patients, systemic thrombolysis was associ-
ated with significantly more clot lysis (relative risk [RR] 0.24
to 0.37) and significantly less PTS (RR 0.66). However, venous
function was not significantly improved. In addition, more
bleeding complications occurred (RR 1.73).
In an effort to minimize bleeding complications and
increase efficacy, CDT techniques were developed for the treat-
ment of symptomatic primarily iliofemoral DVT. With catheter-
directed therapy, venous access may be achieved through
percutaneous catheterization of the ipsilateral popliteal vein,
retrograde catheterization through the contralateral femoral
vein, or retrograde cannulation from the internal jugular vein.
Multi–side-hole infusion catheters, with or without infusion
wires, are used to deliver the lytic agent directly into the throm-
bus. Lytic agents may be administered alone or, now more
commonly, in combination with catheter-based methods to

http://ebook2book.ir/
physically break up the clot—so-called pharmacomechanical
thrombolysis. One commonly used device to perform phar-
macomechanical thrombolysis is the AngioJet, which utilizes
pulsed injection of thrombolytic via a percutaneously inserted
catheter followed by active aspiration to remove the thrombus.
The efficacy of CDT for the treatment of symptomatic
iliofemoral DVT has been reported previously in a large, multi-
center, randomized control trial. Two-hundred and nine patients
with proximal DVT identified within 21 days of onset of symp-
toms were assigned to conventional anticoagulant therapy vs.
contraindications to anticoagulation, those that have a bleeding 991
complication from anticoagulation therapy of acute VTE, or those
who develop recurrent DVT or PE despite adequate anticoagula-
tion therapy and for patients with severe pulmonary hypertension.
When possible, anticoagulation therapy should be contin-
ued in patients with vena cava filters. The duration of antico-
agulation is determined by the underlying VTE and not by the
presence of the IVC filter itself. Practically speaking, however,
many patients who require an IVC filter for recurrent VTE are
the same ones who would benefit most from indefinite antico-

CHAPTER 24 VENOUS AND LYMPHATIC DISEASE

conventional anticoagulant therapy plus CDT. In the CDT group, agulation. In patients who are not able to receive anticoagulants
placement of a venous stent was permitted for any identified iliac due to recent surgery or trauma, the clinician should continually
vein stenotic lesion. At 6 months, iliac vein patency was signifi- reassess if anticoagulation may be started safely at a later date.
cantly improved in the thrombolysis group (65.9% vs. 47.4%). Placement of permanent IVC filters has been evaluated as
At 2 years, in the CDT group, there was an absolute risk reduc- an adjunct to routine anticoagulation in patients with proximal
tion of nearly 15% for development of PTS, translating to a num- DVT.62 Routine IVC filter placement has not been shown to
ber needed to treat of seven patients to prevent one case of PTS.60 prolong early or late survival in patients with proximal DVT
However, these results were, in part, contradictory to the results but did decrease the rate of PE (HR, 0.22; 95% CI, 0.05–0.90);
reported the more recent Acute Venous Thrombosis: Throm- however, there is an increased rate of recurrent DVT in patients
bus Removal with Adjunctive Catheter-Directed Thrombolysis with IVC filters (HR, 1.87; 95% CI, 1.10–3.20).
(ATTRACT) trial, a prospective, randomized, multicenter trial IVC filters are associated with acute and late complica-
evaluating nearly 700 patients comparing anticoagulant use with tions. Acute complications include thrombosis or bleeding at the
CDT in patients with acute femoropopliteal, and/or iliac vein insertion site and misplacement of the filter. Late complications
DVT.61 However, the purpose of this trial was to see if indica- include thrombosis of the IVC, DVT, breaking, migration, or ero-
tions for CDT should be extended for isolated femoropopliteal sion of the filter through the IVC (Fig. 24-9). The rate of fatal
DVT (43% of the patients in this study) and therefore, was under- complications is <0.12%.63 As a result of the increasing number
powered to compare treatment efficacy for iliofemoral DVT,
which known to have a higher risk of PTS. The study found that
PTS occurred with equal frequency in the two groups (47% vs.
48%, P = NS), but patients who were treated with pharmacom-
echanical CDT plus anticoagulation were less likely to develop
moderate-to-severe PTS than those treated with anticoagulation
alone (18% vs. 24%, P = .003). There was no difference between
the two groups in quality of life. There was an increase in both
overall hemorrhage (4.5% vs. 1.7%) and major hemorrhage
(1.7% vs 0.3%) with CDT but no fatal or intracranial hemor-
rhage in either cohort. Taken in combination, the findings from
these trials support selective use of CDT with anticoagulation in
young patients with acute iliofemoral DVT and anticoagulation
alone in the remaining patient with DVT.
There are contraindications to thrombolytic therapy.
Absolute contraindications include prior history of ischemic A
or hemorrhagic stroke within 3 months, head trauma within
3 months, neurologic surgery within 6 months, known intra-
cranial neoplasm, internal bleeding within 6 weeks, active or
known bleeding disorder, traumatic cardiopulmonary resuscita-
tion within 3 weeks or suspected aortic dissection. Fortunately,
serious remote bleeding is uncommon, and intracranial hem-
orrhage rarely occurs. The majority of bleeding complications
are limited to the venous access site. Symptomatic pulmonary
embolism occurs uncommonly and is very rarely fatal.
Inferior Vena Caval Filters. Since the introduction of the
Kimray-Greenfield filter in the United States in 1973, numerous
vena caval filters have been developed. Although the designs
are variable, they all are designed to prevent pulmonary emboli,
while allowing continuation of venous blood flow through the
IVC. Early filters were placed surgically through the femoral
vein. Currently, less invasive techniques allow percutaneous
B
filter placement through a femoral vein, internal jugular vein,
or a peripheral vein under fluoroscopic or ultrasound guidance. Figure 24-9. Preoperative computed tomography imaging and
Placement of an IVC filter is indicated for patients who intraoperative photo demonstrating erosion of IVC filter through
have manifestations of lower extremity VTE and absolute the IVC wall.

http://ebook2book.ir/
992 of reported complications with IVC filters, the FDA issued a
warning in 2010 recommending removal of IVC filters as soon
as they are no longer needed.64 This was followed by an update in
2014 where the recommendation was made to remove IVC filters
within 29 and 54 days after implantation based upon a mathemati-
cal model that suggested an increased risk-to-benefit ratio at this
time point.65
In some patients, the need for an IVC filter may be self-
limited. Such patients can be treated with so-called removable
IVC filters. Depending on the device, removable IVC filters
are potentially removable by percutaneous endovascular tech-
niques for up to several months after their initial implantation,
PART II

assuming the filter is no longer required and does not have

large amounts of trapped thrombi. IVC filters that have been
in place for an extended period of time may require adjunctive
techniques, including laser-assisted removal or open surgical Figure 24-10. Autopsy specimen showing a massive pulmonary
embolism.
removal when they are embedded within the vena cava. All tem-
SPECIFIC CONSIDERATIONS

porary IVC filters are approved for permanent implantation, and

many so-called temporary filters end up as permanent devices
with all the potential complications of permanent IVC filters.
Operative Venous Thrombectomy. In patients with acute
iliofemoral DVT, surgical therapy is generally reserved for
patients who worsen with anticoagulation therapy and those
with phlegmasia cerulea dolens and impending venous gan-
grene. If the patient has phlegmasia cerulea dolens, a fasciotomy
of the calf compartments is first performed. In iliofemoral DVT,
a longitudinal venotomy is made in the common femoral vein,
and a venous balloon embolectomy catheter is passed through
the thrombus into the IVC and pulled back several times until
no further thrombus can be extracted. The distal thrombus in the
leg is removed by manual pressure beginning in the foot. This
is accomplished by application of a tight rubber elastic wrap
beginning at the foot and extending to the thigh. If the thrombus
in the femoral vein is old and cannot be extracted, the vein may
be ligated. For a thrombus that extends into the IVC, the IVC is
exposed transperitoneally and controlled below the renal veins.
The IVC is opened, and the thrombus is removed by gentle mas-
sage. An intraoperative completion venogram determines if any
residual thrombus or stenosis is present. If a residual iliac vein
stenosis is present, intraoperative angioplasty and stenting can
be performed. In most cases, an arteriovenous fistula is then
created by anastomosing the great saphenous vein (GSV) end
to side with the superficial femoral artery in an effort to main-
tain patency of the thrombectomized iliofemoral venous seg-
ment. Heparin is administered postoperatively for several days.
Warfarin anticoagulation is maintained for at least 6 months
after thrombectomy. Complications of iliofemoral thrombec-
tomy include PE in up to 20% of patients67 and death in <1%
of patients.68
One study followed 77 limbs for a mean of 8.5 years after
thrombectomy for acute iliofemoral DVT. In limbs with suc-
cessful thrombectomy, valvular competence in the thrombecto-
mized venous segment was 80% at 5 years and 56% at 10 years.
More than 90% of patients had minimal or no symptoms of PTS.
There were 12 (16%) early thrombectomy failures. Patients
were required to wear compression stockings for at least 1 year
after thrombectomy.69
Survival rates for surgical pulmonary embolectomy have
improved over the past 20 years with the addition of cardio-
pulmonary bypass. Emergency pulmonary embolectomy for
acute PE is rarely indicated. Patients with preterminal massive
PE (Fig. 24-10) for whom thrombolysis has failed or who have
contraindications to thrombolytics may be candidates for this
procedure. Open pulmonary artery embolectomy is performed
through a posterolateral thoracotomy with direct visualization
of the pulmonary arteries. Mortality rates range between 20%
and 40%.70-72
Percutaneous catheter-based techniques for removal of a
PE involve mechanical thrombus fragmentation or embolec-
tomy using suction devices. Mechanical clot fragmentation is
followed by CDT. Results of catheter-based fragmentation are
based on small case series. In a study in which a fragmentation
device was used in 10 patients with acute massive PE, frag-
mentation was successful in 7 patients with a mortality rate of
20%.73 Transvenous catheter pulmonary suction embolectomy
has also been performed for acute massive PE with a reported
76% successful extraction rate and a 30-day survival of 70%.74
Prophylaxis
Patients who undergo major general surgical, gynecologic,
urologic, and neurosurgical procedures without thrombopro-
phylaxis have a significant incidence of perioperative DVT.
An estimated one-third of the 150,000 to 200,000 VTE-related
deaths per year in the United States occur following surgery.75
The goal of prophylaxis is to reduce the mortality and morbidity
associated with VTE. The first manifestation of VTE may be a
life-threatening PE (Fig. 24-11), and as indicated earlier, clinical
evaluation to detect DVT before PE is unreliable.
Effective methods of VTE prophylaxis involve the use
of one or more pharmacologic or mechanical modalities. Cur-
rently available pharmacologic agents include low-dose UFH,
LMWH, synthetic pentasaccharides, and vitamin K antago-
nists. Mechanical methods include intermittent pneumatic com-
pression (IPC) and graduated compression stockings. There
is insufficient evidence to consider aspirin alone as adequate
DVT prophylaxis. Methods of prophylaxis vary with regard to
efficacy, and the 2012 ACCP Clinical Practice Guidelines strat-
ify their uses according to the patient’s level of VTE risk, bleed-
ing risk, and the values and preferences of individual patients
(see Table 24-3).
Venous Thromboembolism Prophylaxis in Nonorthopedic
Surgery. The risk for VTE associated with a surgical procedure
depends on the type of operation, type of anesthesia, duration
of surgery, and other risk factors, such as patient age, presence
of cancer, prior VTE, obesity, presence of infection, and known
thrombophilic disorders. VTE risk can be stratified according to

http://ebook2book.ir/
 Table 24-5 993

Risk assessment model from the Patient Safety in

Surgery Study
RISK FACTOR RISK SCORE POINTS
Operation type other than endocrine
Respiratory and hernia 9
Thoracoabdominal aneurysm, 7
embolectomy/thrombectomy,

CHAPTER 24 VENOUS AND LYMPHATIC DISEASE

venous reconstruction, and
endovascular repair
Aneurysm 4
Mouth, palate 4
Stomach, intestines 4
Integument 3
Hernia 2
ASA, physical status classification
Figure 24-11. Computed tomography angiogram showing mul-
3,4, or 5 2
tiple pulmonary embolisms (arrows). (Used with permission from
2 1
Dr. Scott Ambruster.)
Female sex 1
Work RVU
the previously mentioned risk assessment models, the Caprini >17 3
score and Rogers score. These risk assessment models are 10–17 2
included in the prophylaxis guidelines for nonorthopedic sur- Two points for each of these 2
gery (Tables 24-5 and 24-6). A composite score is created using conditions
assigned values for each risk factor. The cumulative score for Disseminated cancer
each patient is then used to predict thrombosis risk and provide Chemotherapy for malignancy within
recommendations regarding VTE prophylaxis. 30 days of operation
Patients at very low risk (<0.5%; Rogers score <7; Preoperative serum sodium
Caprini score 0) who undergo general or abdominopelvic >145 mmol/L
procedures do not require pharmacologic or mechanical pro- Transfusion >4 units packed RBCs
phylaxis; however, early ambulation is required. Patients at in 72 hours before operation
low risk (<1.5%; Rogers score 7–10; Caprini score 1–2) should Ventilator dependent
receive mechanical prophylaxis. Patients at moderate risk (3%; One point for each of these conditions 1
Rogers score >10; Caprini score 3–4) should receive LMWH Wound class (clean/contaminated)
at recommended doses, low-dose UFH, or mechanical pro- Preoperative hematocrit ≤38%
phylaxis. Patients at high risk (6%; Caprini score ≥5) should Preoperative bilirubin >1 mg/dL
receive LMWH at recommended doses or low-dose UFH and Dyspnea
mechanical prophylaxis. Thromboprophylaxis should con- Albumin ≤3.5 mg/dL
tinue until discharge, except in select high-risk patients with Emergency
malignancy in whom extended-duration prophylaxis (up to
Zero points for each of these 0
4–6 weeks) may be beneficial. Patients with significant risk
conditions
for bleeding should receive mechanical prophylaxis until this
ASA physical class of 1
risk subsides.75
Work RVU <10
Overall, low-dose UFH and LMWH reduce the risk for
Male sex
symptomatic and asymptomatic VTE by 60% to 70%. The risks
for bleeding differ, depending on the dosage. Lower dosages ASA = American Society of Anesthesiologists; RBCs = red blood cells;
of LMWH appear to be associated with less bleeding risk than RVU = relative value unit.
Reproduced with permission from Rogers SO Jr, Kilaru RK,
low-dose UFH, but the latter produces less bleeding risk than
Hosokawa P, et al: Multivariable predictors of postoperative venous
higher prophylactic dosages of LMWH.76 Other advantages of thromboembolic events after general and vascular surgery: results
LMWH include once-daily dosing protocols and a lower rate of from the patient safety in surgery study, J Am Coll Surg. 2007
heparin-associated antibody formation. Jun;204(6):1211-1221.
Fondaparinux has been compared with the LMWH dalte-
parin in patients who undergo high-risk major abdominal sur-
gery. It also has been compared with IPC alone in patients Prophylactic insertion of IVC filters has been suggested
undergoing non–high-risk abdominal surgery.77,78 Fondaparinux for VTE prophylaxis in high-risk trauma patients, bariatric
demonstrated rates of VTE prevention, bleeding complications, surgical patients, and some patients with malignancy who
and mortality similar to those of LMWH. It was more beneficial have contraindications for LMWH therapy.79 A 5-year study
than IPC alone in reducing VTE but with a higher rate of bleed- of prophylactic IVC filter placement in 132 trauma patients
ing (1.6% vs. 0.2%). at high risk of PE (head injury, spinal cord injury, pelvic or

http://ebook2book.ir/
994 Table 24-6
Caprini risk assessment model
1 POINT 2 POINTS 3 POINTS 5 POINTS
Age 41–60 Age 61–74 Age ≥75 Stroke (<1 month)
Minor surgery Arthroscopic surgery History of VTE Elective arthroplasty
BMI >25 kg/m 2
Major open surgery Family history of VTE Hip, pelvis, or leg fracture
(> 45 minutes)
Swollen legs Laparoscopic surgery Factor V Leiden Acute spinal cord injury
(> 45 minutes) (<1 month)
PART II

Varicose veins Malignancy Prothrombin 20210A

Pregnancy or postpartum Confined to bed (>72 hours) Lupus anticoagulant
History of unexplained or Immobilizing plaster cast Anticardiolipin antibody
recurrent spontaneous
SPECIFIC CONSIDERATIONS

abortion
Oral contraceptives of Central venous access Elevated serum homocysteine
hormone replacement
Sepsis (<1 month) Heparin-induced
thrombocytopenia
Serious lung disease, including Other congenital or acquired
pneumonia (<1 month) thrombophilia
Abnormal pulmonary
function test
Acute myocardial infarction
Congestive heart failure
History of inflammatory
bowel disease
Medical patient at bed rest
BMI = body mass index; VTE = venous thromboembolism.
Data from Bahl V, Hu HM, Henke PK, et al: A validation study of retrospective venous thromboembolism risk scoring method, Ann Surg. 2010 Feb;
251(2):344-350.

long bone fractures) reported a 0% incidence of symptom-
atic PE in patients with a correctly positioned IVC filter.80 In
47 patients with a malpositioned IVC filter (strut malposition or
filter tilt), there was a 6.3% incidence of symptomatic PE with
three deaths. DVT occurred at the insertion site in 3.1% of the
patients. IVC patency was 97.1% at 3 years.
Fatal and nonfatal PE can still occur in patients with vena
cava interruption. As noted earlier, long-term complications
associated with permanent IVC filters include IVC thrombo-
sis and DVT. Currently, the ACCP recommends IVC filters
be placed only if a proximal DVT is present and anticoagula-
tion therapy is contraindicated. Placement of an IVC filter in
the setting of severe pulmonary embolism development while
anticoagulated remains controversial. IVC filter insertion is not
recommended for primary prophylaxis.75
Removable IVC filters may be placed in patients with
a temporarily increased risk of PE.81 The best patient groups
for retrievable filter placement may include young trauma
patients with transient immobility, patients undergoing surgi-
cal procedures associated with a high risk of PE, and patients
with hypercoagulable states who cannot receive anticoagula-
tion therapy for a short period of time. Careful follow-up is
required to assure all potentially removable filters are in fact
removed.
OTHER VENOUS THROMBOTIC DISORDERS
Superficial Vein Thrombophlebitis
Superficial vein thrombophlebitis (SVT) most commonly
occurs in varicose veins but can occur in normal veins. When
SVT recurs at variable sites in normal superficial veins,
thrombophlebitis migrans, it may signify a hidden visceral
malignancy or a systemic disorder such as a blood dyscrasia
and/or a collagen vascular disease. SVT also frequently occurs
as a complication of indwelling catheters, with or without asso-
ciated extravasation of injected material. Upper extremity vein
thrombosis has been reported to occur in 38% of patients with
peripherally inserted central catheters; 57% of these developed
in the cephalic vein (Fig. 24-12).82 Suppurative SVT may occur
in veins with indwelling catheters and may be associated with
generalized sepsis.
Clinical signs of SVT include redness, warmth, and ten-
derness along the distribution of the affected veins, often asso-
ciated with a palpable cord. Patients with suppurative SVT
may have fever and leukocytosis. DUS should be performed in
patients with signs and symptoms of acute SVT to confirm the
diagnosis and to determine if any associated DVT is present.
Concomitant lower extremity DVT may be present in 5% to
40% of patients with SVT; most occur in patients with greater

http://ebook2book.ir/
 to the subclavian vein, usually where it passes between the head 995
of the clavicle and the first rib in association with the subclavius
muscle. This condition is also known as venous thoracic outlet
syndrome, effort thrombosis, and Paget-Schroetter syndrome.
Secondary ASVT is more common and is associated with an
easily identified cause such as an indwelling catheter or a hyper-
coagulable state. Over 30% of patients with tunneled subclavian
vein access devices develop ASVT.89
A patient with ASVT may be asymptomatic or may pres-
ent with varying degrees of upper extremity edema, tenderness,

CHAPTER 24 VENOUS AND LYMPHATIC DISEASE

and conspicuous superficial venous enlargement. DUS can be
performed initially to confirm the diagnosis, but limitations
to the exam by the clavicle and collateralization can lead to a
false-negative study. Venography is recommended when there
is nonconcordance between the duplex study and clinical suspi-
cion. Anticoagulation therapy should be initiated once ASVT is
Figure 24-12. Duplex ultrasound of a brachial vein containing diagnosed to prevent PE and decrease symptoms.
thrombus and percutaneously inserted central catheter (PICC). Treatment of patients with primary upper extremity venous
thrombosis is controversial because the natural history of the
disease may vary from minimal to no symptoms to significant
saphenous vein SVT within 1 cm of the saphenofemoral symptoms with vigorous upper extremity activities. In recent
junction. A follow-up DUS should be performed in 5 to 7 days years, patients presenting with acute symptomatic primary
in patients with SVT in the proximal GSV but without deep vein ASVT are often considered candidates for CDT therapy with the
involvement. Approximately 10% to 20% of patients with SVT goal of minimizing long-term symptoms of venous congestion.
involving the proximal GSV experience progression to deep Venography is performed through a catheter placed using an
venous involvement within 1 week.83,84 ultrasound-guided percutaneous basilic vein approach to docu-
Treatment of SVT is quite variable. A Cochrane Review ment the extent of the thrombus (Fig. 24-13). A guidewire is
reported that LMWHs and nonsteroidal anti-inflammatory drugs traversed through the thrombus, and a catheter is placed within
both reduce the rate of SVT extension or recurrence.85 Addi- the thrombus. Typically, tissue plasminogen activator is admin-
tionally, a multicenter, randomized, blinded trial comparing use istered through a multi–side-hole infusion catheter. Various
of fondaparinux to placebo in lower extremity SVT found use catheter-based mechanical techniques may also be employed to
of fondaparinux reduced the rate of VTE formation by 85%, speed thrombus removal. Heparin is administered concurrently
though the incidence of VTE formation was low in both groups with the thrombolytic infusion. After completion of thrombo-
(0.2% vs. 1.3%, P <.001). The number needed to treat to prevent lytic therapy, a follow-up venogram is obtained. Correctable
one episode of VTE was 88 patients. There was no difference in anatomic abnormalities may then be considered for treatment.
mortality between the two arms of the trial.85 Adjuvant procedures after thrombolytic therapy may include
Topical medications appear to improve local symptoms.
Surgical treatment, combined with the use of graduated com-
pression stockings, is associated with a lower rate of VTE and
SVT progression.86 The treatment is individualized and depends
on the location of the thrombus and the severity of symptoms.
In patients with SVT not within 1 cm of the saphenofemoral
junction, treatment consists of compression and administra-
tion of an anti-inflammatory medication such as indomethacin.
In patients with suppurative SVT, antibiotics and removal of
any existing indwelling catheters are mandatory. Excision of
the vein may be necessary but is usually reserved for patients
with systemic symptoms or when excision of the involved vein
is straightforward. If the SVT extends proximally to within
1 cm of the saphenofemoral junction, extension into the com-
mon femoral vein is more likely to occur. In these patients,
anticoagulation therapy for 6 weeks and GSV ligation appear
equally effective in preventing thrombus extension into the deep
venous system.87,88
Upper Extremity Vein Thrombosis
Axillary-subclavian venous thrombosis (ASVT) is classified
into two forms. Primary ASVT occurs in only a small minority
of all patients with ASVT. In the primary form, no clear cause
for the thrombosis is readily identifiable at initial evaluation.
Patients with primary ASVT often give a history of performing Figure 24-13. Upper extremity venogram showing stenosis of the
prolonged, repetitive motion activities, which results in damage right subclavian vein at the first rib (arrow).

http://ebook2book.ir/
996 cervical or first rib resection for thoracic outlet abnormalities,
scalenectomy, surgical venous reconstruction, and balloon
angioplasty of residual venous stenosis.90 The ACCP guidelines
recommend the same intensity and duration of anticoagulant
therapy in patients who undergo thrombolysis as in patients who
are treated with anticoagulation alone.
Mesenteric Vein Thrombosis
Five percent to 15% of cases of acute mesenteric ischemia occur
as a result of mesenteric vein thrombosis (MVT). Mortality rates
in patients with MVT may approach 50%.91 The usual present-
ing symptom is nonspecific abdominal pain and distention,
PART II
often accompanied by nausea, vomiting, and diarrhea.92 Perito-
neal signs, suggesting intestinal infarction, are present in fewer
than half of MVT patients. MVT is more common in patients
with a hypercoagulable states, malignancy, and cirrhosis. MVT
also occurs as a rare complication of laparoscopic surgery.92,93
SPECIFIC CONSIDERATIONS
Most cases of MVT are diagnosed with contrast-enhanced
CT scanning or magnetic resonance imaging (MRI) in the course
of an evaluation for abdominal pain. The sensitivity and speci-
ficity for CT and MRI approach 100% and 98%, respectively.94
Ultrasound can also be used and has reported sensitivity and
specificity of 93% and 99%, respectively.
Patients with MVT are treated with fluid resuscitation,
heparin anticoagulation, and bowel rest. Once the patient’s
clinical status improves, oral intake can be carefully started. The
patient is transitioned to oral anticoagulation over 3 to 4 days
and, depending on the etiology of the MVT, continued for 3 to
6 months or indefinitely. Most patients with MVT can be treated
nonoperatively, but urgent laparotomy is indicated in patients
with peritoneal findings. Broad-spectrum antibiotics are admin-
istered perioperatively. Operative findings consist of edema
and cyanotic discoloration of the mesentery and bowel wall. In
more advanced cases, thrombus involves the distal mesenteric
veins. The arterial supply to the involved bowel is usually intact.
Nonviable bowel is resected, and primary anastomosis can be
performed. If the viability of the remaining bowel is in question,
a second-look operation is performed within 24 to 48 hours.
VARICOSE VEINS
Varicose veins are common and are present in at least 10% of
the general population.95 The findings of varicose veins may
include dilated and tortuous veins, telangiectasias, and fine
reticular varicosities. Risk factors for varicose veins include
obesity, female sex, inactivity, and family history.96 Varicose
veins can be classified as primary or secondary. Primary vari-
cose veins result from intrinsic abnormalities of the venous wall,
whereas secondary varicose veins are associated with deep and/
or superficial venous insufficiency.
Patients with varicose veins may complain of unsightly
appearance, aching, heaviness, pruritus, and early fatigue of the
affected leg. These symptoms worsen with prolonged standing and
sitting and are relieved by elevation of the leg above the level of
the heart. A mild amount of edema is often present. More severe
signs include thrombophlebitis, hyperpigmentation, lipodermato-
sclerosis, ulceration, and bleeding from attenuated vein clusters.
An important component of treatment for patients with vari-
cose veins is the use of elastic compression stockings. Patients
may be prescribed elastic stockings with compression ranging
from 20 to 30, 30 to 40, or even 40 to 50 mmHg. Stockings range
in length from knee high to waist high, and they should cover
http://ebook2book.ir/
the symptomatic varices. Elastic compression provides sufficient
relief of symptoms in many symptomatic patients.
Cosmetic concerns may lead to intervention. Addition-
ally, interventions are warranted in patients whose symptoms
worsen or are unrelieved despite compression therapy or who
have lipodermatosclerosis or venous ulcer. Randomized trials
of symptomatic patients with varicose veins have demonstrated
improved quality of life with interventional treatment. Interven-
tional management includes injection sclerotherapy, thermal
ablation, surgical therapy, or a combination of these techniques.
Injection sclerotherapy alone can be successful in varicose veins
and in telangiectatic vessels. A recent multicenter, randomized
trial compared foam sclerotherapy versus placebo for symp-
tomatic varicose veins found significant symptom relief and
improved cosmetic appearance with sclerotherapy.97 Sclero-
therapy acts by destroying the venous endothelium. Scleros-
ing agents include hypertonic saline, sodium tetradecyl sulfate,
and polidocanol. Concentrations of 11.7% to 23.4% hypertonic
saline, 0.125% to 0.250% sodium tetradecyl sulfate, and 0.5%
polidocanol are used for telangiectasias. Larger varicose veins
require higher concentrations: 23.4% hypertonic saline, 0.50% to
1% sodium tetradecyl sulfate, and 0.75% to 1.0% polidocanol.92
Elastic bandages are wrapped around the leg after injection and
worn continuously for 3 to 5 days to produce apposition of the
inflamed vein walls and prevent thrombus formation. After the
bandages are removed, elastic compression stockings should be
worn for a minimum of 2 weeks. Complications from sclero-
therapy include allergic reaction, local hyperpigmentation,
thrombophlebitis, DVT, and possible skin necrosis.
Newer devices combine sclerotherapy with catheter-based
mechanical endoluminal injury to achieve nonthermal ablation.98
Additional nonthermal, nonsclerosant ablative techniques using
proprietary adhesive formulations with cyanoacrylate are current
being evaluated and have demonstrated promising early results.99
Patients with symptomatic GSV or SSV reflux may be
treated with endovenous ablation techniques or surgical removal
of the affected vein. Endovenous laser and radiofrequency abla-
4 tion (RFA) techniques have gained in popularity in the
past several years. Such techniques are generally associ-
ated with equally effective but more rapid postprocedure recov-
ery than traditional open surgical stripping of the GSV.
With either endoluminal technique, the distal thigh or
proximal calf GSV is punctured with a 21-gauge needle under
ultrasound guidance. A sheath is placed over a guidewire, and
the laser fiber or RFA catheter is advanced until it is near to,
but not at, the saphenofemoral junction. Tumescent anesthetic
is administered around the GSV, and the vein is treated as the
catheter is withdrawn. Endovenous laser treatment and RFA
result in durable ablation of the GSV, with rates of varicose vein
recurrence and clinical severity scores comparable to those seen
with open surgery.100,101 Risks of endovenous ablation include
DVT, ecchymosis, and saphenous nerve injury.
Saphenous vein ligation and stripping may still be the pre-
ferred therapy for patients with GSVs of very large diameter
(>2 cm). Surgical removal of the GSV usually is performed via
small incisions placed medially in the groin and just below the
knee. The GSV is removed using a blunt tip catheter or an invagi-
nation pin stripper. Complications associated with GSV stripping
include ecchymosis, hematoma, lymphocele, DVT, infection, and
saphenous nerve injury. GSV stripping is associated with a lower
rate of recurrence of varicose veins and a better quality of life than
saphenofemoral junction ligation alone.

Figure 24-14. Removal of varicose veins via stab avulsions.
Larger varicose veins are best treated by surgical exci-
sion using the “stab avulsion” technique. Stab avulsions are
performed by making 2-mm incisions directly over branch
varicosities, and the varicosity is dissected from the surrounding
subcutaneous tissue as far proximally and distally as possible
through the small incisions (Fig. 24-14). In most cases the vein
is simply avulsed with no attempt at ligation. Bleeding is easily
controlled with leg elevation, manual compression, and prepro-
cedure tumescent anesthesia.
CHRONIC VENOUS INSUFFICIENCY
Chronic venous insufficiency (CVI) affects an estimated
600,000 people in the United States.102 Patients complain of leg
fatigue, discomfort, and heaviness. Signs of CVI may include
varicose veins, pigmentation, lipodermatosclerosis, and venous
ulceration. Importantly, severe CVI is not necessarily associ-
ated with varicose veins. Chronic venous ulcers carry significant
negative physical, financial, and psychological implications. A
quality-of-life study reported that 65% of patients with chronic
leg ulcers had severe pain, 81% had decreased mobility, and
100% experienced a negative impact of their disease on their
work capacity.103 The socioeconomic impact of chronic venous
leg ulcers is staggering, with an estimated 2 million workdays
lost per year.102 The annual healthcare cost in the United States
to treat CVI is estimated at $1 billion.105
CVI can be primary or secondary. Primary CVI results
from intrinsic abnormalities of the vein wall, whereas second-
ary CVI, so-called postthrombotic syndrome (PTS), occurs as a
result of DVT. The signs and symptoms of CVI can therefore be
attributed to venous reflux, venous obstruction, calf muscle pump
dysfunction, or a combination of these factors, as well as loss of
venous wall elasticity.106 In the majority of patients with CVI,
the most important factor appears to be venous reflux, although
most severe cases tend to have an obstructive etiology as well.
Venous reflux results from abnormalities of the venous valve.
Primary valvular reflux or incompetence is diagnosed when there
is no known underlying cause of valvular dysfunction. Secondary
valvular reflux is diagnosed when an identifiable cause is present.
The most frequent secondary cause is DVT.
Evaluation of Venous Insufficiency
Early diagnostic studies to evaluate CVI required invasive mea-
surements of ambulatory venous pressure (AVP) and venous
recovery time (VRT). To measure AVP and VRT, a needle
http://ebook2book.ir/
is inserted into a dorsal foot vein and connected to a pressure 997
transducer. The patient is asked to perform 10 tiptoe exercises.
Initially there is often a slight upward deflection of pressure
with the onset of exercise followed by a decline in pressure
with each subsequent tiptoe maneuver. After approximately
10 tiptoes, the measured pressure stabilizes and reflects a bal-
ance of venous inflow and outflow. The pressure at this point
is the AVP, which is measured in millimeters of mercury.
The patient is then asked to stop exercising to allow the vein
to fill with return of the venous pressure to baseline. The time
CHAPTER 24 VENOUS AND LYMPHATIC DISEASE
required for the venous pressure to return from the AVP level
to 90% of baseline pressure is referred to as the VRT. A normal
VRT typically ranges from 20 to 60 seconds. Values less than
20 seconds indicate significant reflux with increasing severity.
To distinguish between superficial and deep venous reflux, a
thigh tourniquet can be placed inflated to 50 mmHg to eliminate
influence of the superficial venous. A VRT that remains below
20 seconds after tourniquet inflation suggests both superficial
and deep venous reflux. Elevations of AVP indicate venous
hypertension. The magnitude of AVP reflects the severity of
CVI. There is an 80% incidence of venous ulceration in patients
with an AVP of >80 mmHg.107
Plethysmography. Noninvasive plethysmography has been
used to evaluate CVI. Venous photoplethysmography indirectly
evaluates venous function through the use of infrared light. A
light-emitting diode is placed just above the medial malleolus,
and the patient then performs a series of tiptoe maneuvers. Pho-
toplethysmography provides a measurement of VRT. In limbs
with CVI, VRT is shortened compared with that in a normal
limb. AVP and VRT are only measures of the overall venous
function of a lower extremity venous system. They cannot local-
ize the site of reflux or evaluate the function of the calf pump.
Air plethysmography is a theoretically attractive but
not widely used method to assess calf pump function, venous
reflux, and overall lower extremity venous function.108 An air-
filled plastic pressure bladder is placed on the calf to detect
volume changes in the leg during a standard set of maneuvers.
The patient is first supine, and then the leg is elevated and the
minimum volume of venous blood recorded. The patient is
then asked to assume an upright position with the examined leg
non-weight bearing. The venous volume of the examined leg
is determined when the volume curve flattens. The venous fill-
ing index (VFI), a measure of reflux, is calculated by dividing
the maximum venous volume by the time required to achieve
maximum venous volume. Next, the patient performs a single
tiptoe maneuver, and the ejection fraction (EF) is determined.
The EF is the volume change between the recorded volume
before and after the tiptoe maneuver and is a measure of calf
pump function. At this point, the veins of the leg are allowed to
refill. The patient then performs 10 tiptoe maneuvers, and the
residual volume fraction is calculated by dividing the venous
volume in the leg after 10 tiptoe exercises by the venous volume
present before the exercises. The residual volume fraction is
a reflection of overall venous function. Theoretically, patients
with increased VFIs and normal EFs (indicating the presence of
reflux with normal calf pump function) would benefit from anti-
reflux surgery, whereas patients with normal VFIs and dimin-
ished EFs would not.
Venous Duplex Ultrasound. Venous DUS has become
the gold standard for evaluation of venous function largely
supplanting venographic and plethysmographic techniques.
998
PART II
Figure 24-15. Evaluation of a patient with chronic venous insuf-
ficiency with duplex ultrasonography.
SPECIFIC CONSIDERATIONS
The principle advantage of DUS is that it can be used to evalu-
ate reflux in individual venous segments targeting abnormal
areas for treatment. The examination has been validated when
performed with the patient in the standing position and the
examined leg non-weight bearing. Pneumatic pressure cuffs
of appropriate size are placed around the thigh, calf, and fore-
foot. The ultrasound transducer is positioned over the venous
segment to be examined, just proximal to the pneumatic cuff
(Fig. 24-15). The cuff is then inflated to a standard pressure
for 3 seconds and then rapidly deflated. Ninety-five percent of
normal venous valves close within 0.5 second.109 The presence
of reflux for >0.5 second is considered abnormal. Typically,
the common femoral, femoral, popliteal, and posterior tibial
veins, as well as the GSV and SSV, are evaluated in a complete
examination.
Nonoperative Treatment of Chronic Venous Insufficiency
Compression Therapy. Compression therapy is the mainstay
of CVI management. Compression can be achieved using a vari-
5 ety of techniques, including elastic compression stockings,
paste gauze boots (Unna’s boots), multilayer elastic wraps
or dressings (Fig. 24-16), and pneumatic compression devices.
Nonelastic compression bandages generally achieve higher and
more prolonged degrees of compression than elastic compression
bandages. The exact mechanism by which compression therapy
can improve CVI remains uncertain. An improvement in skin and
Figure 24-16. Multilayered dressing for treatment of chronic
venous insufficiency.
http://ebook2book.ir/
subcutaneous tissue microcirculatory hemodynamics as well as a
direct effect on subcutaneous pressure have been hypothesized as
the mechanisms of efficacy of compression therapy.110 Addition-
ally, compression therapy has demonstrated quantifiable differ-
ences in ulcer healing with decreases in matrix metalloproteins
and inflammatory cytokines.111,112 Clinically, routine use of elastic
and nonelastic bandages reduces lower extremity edema in
patients with CVI. In addition, supine perimalleolar subcutaneous
pressure has been demonstrated to increase with elastic
compression.111 With edema reduction, cutaneous metabolism
may improve due to enhanced diffusion of oxygen and other
nutrients to the cellular elements of skin and subcutaneous tissues.
Increases in subcutaneous tissue pressure with elastic compres-
sion bandages may counteract transcapillary Starling forces,
which favor leakage of fluid out of the capillary.
Before the initiation of therapy for CVI, patients must be
educated about their chronic disease and the need to comply
with their treatment plan to heal ulcers and prevent recurrence.
A definitive diagnosis of venous ulceration must be made before
treatment is initiated. A detailed history should be obtained from
a patient presenting with lower extremity ulcerations, includ-
ing medications used and associated medical conditions that
may promote lower extremity ulceration. Arterial insufficiency
is assessed by physical examination or noninvasive studies. In
addition, systemic conditions that affect wound healing and leg
edema, such as diabetes mellitus, immunosuppression, mal-
nutrition, and congestive heart failure, should be improved as
much as possible.
Compression therapy is most commonly achieved with
graduated elastic compression stockings. Elastic compression
stockings are available in various compositions, strengths, and
lengths, and can be customized for a particular patient. The ben-
efits of elastic compression stocking therapy for the treatment of
CVI and healing of ulcerations have been well documented.114-117
In a retrospective study involving 113 venous ulcer patients,115
the use of below-knee, 30- to 40-mmHg elastic compression
stockings, after edema and cellulitis were first resolved if pres-
ent, resulted in 93% healing. Complete ulcer healing occurred in
99 of 102 patients (97%) who were compliant with stocking use
vs. 6 of 11 patients (55%) who were noncompliant (P <.0001).
The mean time to ulcer healing was 5 months. The rate of ulcer
recurrence was lower in patients who were compliant with their
compression therapy. By life table analysis, ulcer recurrence
was 29% at 5 years for compliant patients and 100% at 3 years
for noncompliant patients.
In addition to promoting ulcer healing, elastic compres-
sion therapy can also improve quality of life in patients with
CVI. In one prospective study,118 112 patients with CVI docu-
mented by DUS were administered a questionnaire to quantify
the symptoms of swelling, pain, skin discoloration, cosmesis,
activity tolerance, depression, and sleep alterations. Patients
were treated with 30- to 40-mmHg elastic compression stock-
ings. There were overall improvements in symptom severity
scores at 1 month after initiation of treatment. Further improve-
ments were noted at 16 months after treatment.
Patient compliance with compression therapy is crucial in
treating CVI and especially venous leg ulcers. Many patients
are initially intolerant of compression in areas of hypersensitiv-
ity adjacent to an active ulcer or at sites of previously healed
ulcers. They may also have difficulty applying elastic stockings.
To improve compliance, patients should be instructed to wear
their stockings initially only as long as it is easily tolerated and

Figure 24-17. Elastic compression device with Velcro to facilitate
treatment of chronic venous insufficiency.
then gradually to increase the amount of time the stockings are
worn. Alternatively, patients can be fitted with lower-strength
stockings initially followed by introduction of higher-strength
stockings over a period of several weeks. Many commercially
available devices, such as silk inner toe liners, adjustable elas-
tic compression with Velcro, stockings with zippered sides
(Fig. 24-17), and metal fitting aids (Fig. 24-18), are available to
assist patients in applying elastic stockings. However, despite
all these available adjuncts, many patients remain noncompliant
with elastic compression therapy.
Another method of compression was developed by the
German dermatologist Paul Gerson Unna. Unna’s boot has been
used for many years to treat venous ulcers and is available in
many versions. A typical Unna’s boot consists of a three-layer
dressing and requires application by trained personnel. A rolled
gauze bandage impregnated with calamine, zinc oxide, glyc-
erin, sorbitol, gelatin, and magnesium aluminum silicate is first
applied with graded compression from the forefoot to just below
the knee. The next layer consists of a 10-cm-wide continuous
gauze dressing followed by an outer layer of elastic wrap, also
applied with graded compression. The bandage becomes stiff
after drying, and the rigidity may aid in preventing edema for-
mation. Unna’s boot is changed weekly or sooner if the patient
experiences significant drainage and soiling of the dressing.
Once applied, Unna’s boot requires minimal patient
involvement and provides continuous compression and topical
therapy. However, Unna’s boot has several disadvantages. It
http://ebook2book.ir/
999
CHAPTER 24 VENOUS AND LYMPHATIC DISEASE
Figure 24-18. Metal fitting aid to assist in placement of elastic
compression stockings.
is bulky and can be uncomfortable, which may affect patient
compliance. In addition, the ulcer cannot be monitored after the
boot is applied, the technique is labor intensive, and the degree
of compression provided is operator dependent. Occasionally,
patients may also develop contact dermatitis to the components
of Unna’s boot.
The efficacy of Unna’s dressing has been studied. A ret-
rospective 15-year survey encompassing 998 patients with one
or more venous ulcers treated weekly with Unna’s dressing119
reported that 73% of ulcers healed in patients who returned
for more than one treatment. The median time to healing for
individual ulcers was 9 weeks. Unna’s dressing has been com-
pared to other forms of treatment. A randomized, prospective
study comparing Unna’s boot to polyurethane foam dressing in
36 patients with venous ulcers demonstrated superior healing
over 12 months in patients treated with Unna’s boot (94.7%
vs. 41.2%).120 A recent Cochrane Review of 39 randomized
controlled trials demonstrated that compression increases ulcer
healing rates compared with no compression, multicomponent
systems are more effective than single-component systems,
and multicomponent systems that include an elastic bandage
are more effective than those composed mainly of inelastic
constituents.121
Other forms of compression dressing available to treat
CVI include multilayered dressings and legging orthoses. The
purported advantages of multilayered dressings include main-
tenance of compression for a longer period of time, more even
distribution of compression, and better absorption of wound
1000 exudates. However, the efficacy of multilayered dressings
depends on the wrapping technique of healthcare personnel. A
commercially available legging orthosis consisting of multiple
adjustable loop-and-hook closure compression bands provides
compression similar to that of Unna’s boot and can be applied
daily by the patient.122
Skin Substitutes. Several types of skin substitutes are com-
mercially available or under clinical study in the United States.105
Bioengineered skin ranges in composition from acellular skin
substitutes to partial living skin substitutes. Their mechanism
of action in healing venous ulcers is uncertain; however, they
PART II
may serve as delivery vehicles for various growth factors and
cytokines important in wound healing.
Apligraf is a commercially available bilayered living skin
construct that closely approximates human skin for use in the
treatment of venous ulcers. It contains a protective stratum
SPECIFIC CONSIDERATIONS
corneum and a keratinocyte-containing epidermis overlying a
dermis consisting of dermal fibroblasts in a collagen matrix.122
Apligraf is between 0.5 mm and 1.0 mm thick and is supplied
as a disk of living tissue on an agarose gel nutrient medium. It
must be used within 5 days of release from the manufacturer123
(Fig. 24-19). The disk is easily handled and applied and con-
forms to irregularly contoured ulcer beds though it is very costly.
A prospective randomized study comparing multilayer
compression therapy alone to treatment with Apligraf in addi-
tion to multilayered compression therapy has been performed
to assess the efficacy of Apligraf in the treatment of venous
ulcers.118 More patients treated with Apligraf had ulcer healing
at 6 months (63% vs. 49%, P = .02). The median time to com-
plete ulcer closure was significantly shorter in patients treated
with Apligraf (61 days vs. 181 days, P = .003). The ulcers that
showed the greatest benefit with the living skin construct were
ones that were large and deep (>1000 mm2) or were longstand-
ing (>6 months). No evidence of rejection or sensitization has
been reported in response to Apligraf application.
Surgical/Interventional Treatment of Chronic Venous
Insufficiency Perforator Vein Ligation. Incompetence
of the perforating veins connecting the superficial and deep
venous systems of the lower extremities has been implicated
in the development of venous ulcers. The classic open tech-
nique described by Linton in 1938 for perforator vein ligation
has a high incidence of wound complications and has largely
been abandoned.124 A minimally invasive technique termed
Figure 24-19. Apligraf skin graft material supplied as a disk on an
agarose gel nutrient medium.
http://ebook2book.ir/
subfascial endoscopic perforator vein surgery (SEPS) evolved
with improvement of endoscopic equipment.
DUS is performed preoperatively in patients undergoing
SEPS to document deep venous competence and to identify per-
forating veins in the posterior compartment. The patient is posi-
tioned on the operating table with the affected leg elevated at
45° to 60°. An Esmarch bandage and a thigh tourniquet are used
to exsanguinate the limb. The knee is then flexed, and two small
incisions are made in the proximal medial leg away from areas
of maximal induration at the ankle. Laparoscopic trocars are
then positioned, and the subfascial dissection is performed with
a combination of blunt and sharp dissection. Carbon dioxide is
then used to insufflate the subfascial space. The thigh tourni-
quet is inflated to prevent air embolism. The perforators are then
identified and doubly clipped and divided. After completion of
the procedure, the leg is wrapped in a compression bandage for
5 days postoperatively.
The efficacy of SEPS as a stand-alone procedure in
treatment of venous insufficiency is controversial and unproven.
In a report from a large North American registry of 146 patients
undergoing SEPS125 (Fig. 24-20), healing was achieved in 88%
of ulcers (75 of 85) at 1 year. Adjunctive procedures, primarily
superficial vein stripping, were performed in 72% of patients.
Ulcer recurrence was predicted to be 16% at 1 year and 28% at
2 years by life table analysis. These results are similar to those
achieved in some studies with compression therapy alone.
A review of several studies from 2003 to 2011 demonstrated, when
taken in aggregate, that 2059 limbs with 896 ulcers underwent
SEPS and concomitant saphenous vein ablation (70%) with a 0%
to 16% complication rate and achieved ulcer healing in 90% of
patients.126 There has been a multicenter, prospective, European
trial performed in patients with venous ulcers to evaluate the
efficacy of SEPS. Post hoc analysis suggested possible benefit
for SEPS in certain categories of patients with venous ulcer.
Overall, however, primary analysis of the study’s end points
indicated no advantage to SEPS in addition to superficial venous
surgery and compression in the healing of venous ulcers.127 The
technique appears to have fallen out of favor in most institutions
with injection sclerotherapy preferred due to ease of use.
Superficial Venous Surgery. Currently it is accepted that
superficial venous surgery in addition to compression therapy
has a role in the treatment of patients with venous ulcer. The
ESCHAR trial was a randomized prospective trial performed in
the United Kingdom to evaluate the combination of superficial
Figure 24-20. Trocar placement for subfascial endoscopic perfo-
rator vein surgery. (Used with permission from Dr. Pankaj Patel.)
venous surgery and compression vs. compression alone in the
treatment of venous ulcer. Superficial venous surgery had no
additive effect to compression alone in the healing of a venous
ulcer but significantly reduced venous ulcer recurrence at
4 years. Based on the results of this trial, it is reasonable to
offer ablation or removal of the GSV in addition to compression
therapy in patients with abnormal saphenous veins and signs
and/or symptoms of severe CVI.128
Deep Venous Valvular Reconstruction. In the absence of sig-
nificant deep vein valvular incompetence, saphenous vein stripping
of age and may be associated with specific hereditary syndromes 1001
(Turner syndrome, Milroy syndrome, Klippel-Trénaunay-Weber
syndrome). Lymphedema praecox is the most common form of
primary lymphedema, accounting for 94% of cases. Lymphedema
praecox is far more common in women, with the gender ratio
favoring women 10:1. The onset is during childhood or the teen-
age years, and the swelling involves the foot and calf. Lymph-
edema tarda is uncommon, accounting for <10% of cases of
primary lymphedema. The onset of edema is after 35 years of age.
Secondary lymphedema is far more common than primary

CHAPTER 24 VENOUS AND LYMPHATIC DISEASE

and possibly perforator vein ligation can be effective in the treat- lymphedema. Secondary lymphedema develops as a result of
ment of CVI. However, in patients with a combination of superfi- lymphatic obstruction or disruption. Axillary node dissection
cial and deep vein valvular incompetence, the addition of deep vein leading to lymphedema of the arm is the most common cause
valvular reconstruction theoretically may improve ulcer healing.130 of secondary lymphedema in the United States. Other causes
Numerous techniques of deep vein valve correction have been of secondary lymphedema include radiation therapy, trauma,
reported. These techniques consist of repair of existing valves, infection, and malignancy. Globally, filariasis (an infection
transplant of venous segments from the arm, transposition of an caused by Wuchereria bancrofti, Brugia malayi, and Brugia
incompetent vein onto an adjacent competent vein, and implanta- timori) and environmental exposure to minerals in volcanic soil
tion of cryopreserved vein segments including competent valves. resulting in podoconiosis in barefoot populations are the most
Successful long-term outcomes of 60% to 80% have been common causes of secondary lymphedema.
reported for venous valve reconstructions by internal suture Clinical Diagnosis
repair.129,130 However, among patients who initially had ulcer- In most patients, the diagnosis of lymphedema can be made based
ation, 40% to 50% still had persistence or recurrence of ulcers on the history and physical examination alone. Patients commonly
in the long term.127,129 complain of heaviness and fatigue in the affected extremity. The
Valve transplantation involves replacement of a segment limb size increases throughout the day and decreases to some
of incompetent femoral vein or popliteal vein with a segment extent, usually minimally, over the course of the night when the
of axillary or brachial vein with competent valves. Early results patient is recumbent. The limb, however, never completely nor-
are similar to those for venous valve reconstruction.129,130 How- malizes. In the lower extremity, the swelling classically involves
ever, in the long term, the transplanted venous segments tend the dorsum of the foot, and the toes have a squared-off appear-
to develop incompetence, intimal hyperplasia, and cusp sinus ance. In advanced cases, hyperkeratosis of the skin develops, and
thrombosis with long-term outcomes that are poorer than those fluid weeps from lymph-filled vesicles (Fig. 24-21).
for venous valve reconstructions. The outcomes for venous
transposition are similar to those for valve transplantation.
Currently, reconstruction techniques for deep venous
insufficiency and associated CVI are rarely performed.
Venous Stenting. Currently there is great interest in the role
of venous stents in the treatment of CVI. Stenotic lesions of
the iliac veins, primarily documented with IVUS, are being
reported in a very high percentage of patients with edema, lipo-
dermatosclerosis, or ulceration secondary to venous disease. It
appears possible to percutaneously place stents in the iliac veins
with near 100% technical success and excellent patency of the
stent out to 4 years. Retrospective case series suggest favorable
effects on ulcer healing, symptoms of CVI, and quality of life
in patients with CVI. The role of venous stenting as an indepen-
dent procedure in the treatment of patients with CVI remains an
area of active investigation.131

LYMPHEDEMA
Pathophysiology
Lymphedema is extremity swelling that results from a reduction
in lymphatic transport and accumulation of lymph within the
interstitial space. It is caused by anatomic and or physiologic
abnormalities such as lymphatic hypoplasia, functional insuf-
ficiency, or absence of lymphatic valves.
The original classification system, described by Allen, is
based on the cause of the lymphedema. Primary lymphedema is
6 further subdivided into congenital lymphedema, lymph-
edema praecox, and lymphedema tarda. Congenital lymph-
edema may involve a single lower extremity, multiple limbs, the
genitalia, or the face. The edema typically develops before 2 years Figure 24-21. Patient with severe longstanding lymphedema.

http://ebook2book.ir/
1002 Recurrent cellulitis is a common complication of lymph-
edema. Repeated infection results in further lymphatic damage,
worsening existing disease. The clinical presentation of cellu-
litis ranges from subtle erythema and worsening of edema to a
rapidly progressive soft tissue infection with systemic toxicity.
Many medical conditions can cause edema. If the symp-
toms are mild, distinguishing lymphedema from other causes
of leg swelling can be difficult. Venous insufficiency is often
confused with lymphedema. However, patients with advanced
venous insufficiency typically have lipodermatosclerosis in the
gaiter region, skin ulceration, and/or varicose veins. Bilateral
pitting edema is typically associated with congestive heart fail-
PART II

ure, renal failure, or a hypoproteinemic state.

Radiologic Diagnosis
Duplex Ultrasound. When a patient is evaluated for edema, it
SPECIFIC CONSIDERATIONS

is often difficult to distinguish the early stages of lymphedema

from venous insufficiency. DUS of the venous system can
determine if there is concomitant venous thrombosis or venous
reflux, perhaps contributing to extremity edema. The diagnostic
modalities discussed in the following sections have limited use
in clinical practice. They are invasive and tedious and rarely
change the management of a patient with lymphedema. Most
physicians rely on the patient’s history and physical examina-
tion alone to make the diagnosis of lymphedema.
Lymphoscintigraphy. Lymphoscintigraphy has become the
most commonly, but still overall uncommonly, used diagnostic
test to identify lymphatic abnormalities. It has largely replaced
lymphangiography. A radiolabeled sulfur colloid (technetium
99 m sulfur colloid) is injected into the subdermal, interdigital
region of the affected limb. The lymphatic transport is moni-
tored with a whole-body gamma camera, and major lymphatics Figure 24-22. Lymphoscintigraphy of the lower extremity.
and nodes can be visualized (Fig. 24-22). In normal individu-
als, tracer activity may be detected in the inguinal region within
15 to 60 minutes. Within 3 hours, uptake should be present in
the pelvic and abdominal lymph nodes. In patients with lymph-
edema, various patterns may be seen on lymphoscintigraphy.
There may be delayed or absent transport to the inguinal nodes.
Increased cutaneous collaterals may be seen with obstruction of
the primary axial channels. There may also be localized regions
of reduced uptake in patients with prior node dissection or radia-
tion therapy.
Lymphangiography. Radiologic lymphangiography is per-
formed by first visualizing the lymphatics by injecting colored
dye into the hand or foot. The visualized lymphatic segment
is exposed through a small incision and cannulated with a
27- to 30-gauge needle. An oil-based dye is then injected
slowly into the lymphatics over several hours. The lym-
phatic channels and nodes are then visualized with traditional
radiographs (Figs. 24-23 and 24-24). Lymphangiography is
reserved for patients with lymphangiectasia or lymphatic fis-
tulas, and patients who are being considered for microvascular
reconstruction.

Management
An important aspect of the management of lymphedema is
patient understanding that there is no cure for lymphedema.
The primary goals of treatment are to minimize swelling and
to prevent recurrent infections. Controlling the chronic limb
swelling can improve discomfort, heaviness, and tightness, and
potentially reduce the progression of disease.132 Figure 24-23. Normal lymphangiogram of the pelvis.

http://ebook2book.ir/

Figure 24-24. Normal lymphangiogram of the thigh and lower leg.
Compression Garments. Graded compression stockings are
widely used in the treatment of lymphedema. The stockings
reduce the amount of swelling in the involved extremity by
decreasing edema accumulation while the extremity is dependent.
When worn daily, compression stockings have been associated
with long-term maintenance of reduced limb circumference.134
They may also protect the tissues against chronically elevated
intrinsic pressures, which lead to thickening of the skin and sub-
cutaneous tissue.135 Compression stockings also offer a degree
of protection against external trauma that may lead to cellulitis.
The amount of compression required for controlling
lymphedema ranges from 20 to 60 mmHg and varies among
patients. The stockings can be custom made or prefabricated
and are available in above- and below-knee lengths. The stock-
ings should be worn during waking hours. The garments should
be replaced approximately every 6 months when they lose
elasticity.
Bedrest and Leg Elevation. Elevation is an important aspect
of controlling lower extremity swelling and is often the first
recommended intervention. However, continuous elevation
throughout the day can interfere with quality of life more than
lymphedema itself. Elevation is an adjunct to lymphedema ther-
apy but is not the mainstay of treatment.
Intermittent Pneumatic Compression Therapy. The use of
IPC with a single-chamber or multichamber pump temporar-
ily reduces edema and provides another adjunct to the use of
compression stockings. These devices have been shown to be
effective in reducing limb volume; however, use of compres-
sion stockings is necessary to maintain the volume reduction
when the patient is no longer supine because fluid transport is
not associated with the transport of macromolecules (proteins)
from the tissue. Typically, IPC is used for 4 to 6 hours per day at
home when the patient is supine, with pressure ranges between
30 and 60 mmHg demonstrated to be most effective.135
http://ebook2book.ir/
Lymphatic Massage. Manual lymphatic drainage is a form 1003
of massage developed by Vodder136 that is directed at reduc-
ing edema. In combination with the use of compression stock-
ings, manual lymphatic drainage is associated with a long-term
reduction in edema and fewer infections per patient per year.137
Antibiotic Therapy. Patients with lymphedema are at
increased risk of developing cellulitis in the affected extremity
due to microscopic breakdown in the skin barrier either second-
ary to swelling or unrecognized and untreated tinea pedis. Recur-
rent infection can damage the lymphatics, aggravating the edema
CHAPTER 24 VENOUS AND LYMPHATIC DISEASE
and increasing the risk for subsequent infection. Staphylococcus
and β-hemolytic Streptococcus are the most common organisms
causing soft tissue infection. Aggressive antibiotic therapy and
elevation with compression are recommended at the earliest
signs or symptoms of cellulitis. The drug of choice is penicil-
lin or a cephalosporin active against Streptococcus for 5 days.
In patients with recurrent cellulitis despite methods to reduced
edema, treatment with monthly intramuscular injections of ben-
zathine penicillin 1.2 MU, twice-daily erythromycin 250 mg, or
penicillin V 1 g daily has proven effective at suppression.138
Surgery. A variety of surgical procedures have been devised
for the treatment of lymphedema. Surgical treatment involves
either excision of extra tissue139 or anastomosis of a lymphatic
vessel to another lymphatic or vein.140 In excisional procedures,
part or all of the edematous tissue is removed. This does not
improve lymphatic drainage but debulks redundant tissue. The
microsurgical procedures involve the creation of a lymphati-
colymphatic or lymphaticovenous anastomosis, which theo-
retically improves lymphatic drainage. No long-term follow-up
data are available for these interventions, and therefore opera-
tive therapy for lymphedema is not well accepted worldwide.
Furthermore, operative intervention has the potential to further
obliterate lymphatic channels, worsening the edema.141
SUMMARY
Lymphedema is a chronic condition caused by ineffective
lymphatic transport, which results in edema and skin damage.
Lymphedema is not curable, but the symptoms and long-term
effects can be controlled with a combination of elastic com-
pression stockings, limb elevation, pneumatic compression, and
massage. Controlling the edema protects the skin and potentially
prevents cellulitis.
REFERENCES
Entries highlighted in bright blue are key references.
1. Moncada S, Radomski MW, Palmer RM. Endothelium-
derived relaxing factor. Identification as nitric oxide and role
in the control of vascular tone and platelet function. Biochem
Pharmacol. 1988;37:2495-2501.
2. van Bemmelen PS, Beach K, Bedford G, et al. The mecha-
nism of venous valve closure. Its relationship to the velocity
of reverse flow. Arch Surg. 1990;125:617-619.
3. Moneta GL, Strandness DE, Jr. Basic data concerning nonin-
vasive vascular testing. Ann Vasc Surg. 1989;3:190-193.
4. Neglen P, Berry MA, Raju S. Endovascular surgery in the
treatment of chronic primary and post-thrombotic iliac vein
obstruction. Eur J Vasc Endovasc Surg. 2000;20(6):560-571.
5. Bettman MA, Robbins A, Braun SD, et al. Contrast venogra-
phy of the leg: diagnostic efficacy, tolerance, and complica-
tion rates with ionic and nonionic contrast media. Radiology.
1987;165:113-116.