lower extremity, the superficial venous system includes the greater and lesser

saphenous veins and their tributaries. The deep veins of the leg accompany the major
arteries. Perforating veins connect the superficial and deep systems at multiple
locations. Bicuspid valves are present throughout the venous system to direct the flow
of venous blood centrally.

VENOUS THROMBOSIS

The presence of thrombus within a superficial or deep vein and the accompanying
inflammatory response in the vessel wall is termed venous thrombosis or
thrombophlebitis. Initially, the thrombus is composed principally of platelets and fibrin.
Red cells become interspersed with fibrin, and the thrombus tends to propagate in the
direction of blood flow. The inflammatory response in the vessel wall may be minimal or
characterized by granulocyte infiltration, loss of endothelium, and edema.

The factors that predispose to venous thrombosis were initially described by Virchow in
1856 and include stasis, vascular damage, and hypercoagulability. Accordingly, a
variety of clinical situations are associated with increased risk of venous thrombosis
(Table 232-2). Venous thrombosis may occur in >50% of patients having orthopedic
surgical procedures, particularly those involving the hip or knee, and in 10 to 40% of
patients who undergo abdominal or thoracic operations. The prevalence of venous
thrombosis is particularly high in patients with cancer of the pancreas, lungs,
genitourinary tract, stomach, and breast. Approximately 10 to 20% of patients with
idiopathic deep vein thrombosis have or develop clinically overt cancer; there is no
consensus on whether these individuals should be subjected to intensive diagnostic
workup to search for occult malignancy.

The risk of thrombosis is increased following trauma, such as fractures of the spine,
pelvis, femur, and tibia. Immobilization, regardless of the underlying disease, is a major
predisposing cause of venous thrombosis. This fact may account for the relatively high
incidence in patients with acute myocardial infarction or congestive heart failure. The
incidence of venous thrombosis is increased during pregnancy, particularly in the third
trimester and in the first month postpartum, and in individuals who use oral
contraceptives or receive postmenopausal hormone replacement therapy. A variety of
clinical disorders that produce systemic hypercoagulability, including resistance to
activated protein C (factor V Leiden); prothrombin G20210A gene mutation;
antithrombin III, protein C, and protein S deficiencies; antiphospholipid syndrome;
hyperhomocysteinemia; SLE5 ; myeloproliferative diseases; dysfibrinogenemia; and
disseminated intravascular coagulation, are associated with venous thrombosis.
Venulitis occurring in thromboangiitis obliterans, Behcet's disease, and homocysteinuria
may also cause venous thrombosis.

DEEP VENOUS THROMBOSIS (DVT)

The most important consequences of this disorder are pulmonary embolism (Chap. 244)
and the syndrome of chronic venous insufficiency. DVT6 of the iliac, femoral, or popliteal
veins is suggested by unilateral leg swelling, warmth, and erythema. Tenderness may
be present along the course of the involved veins, and a cord may be palpable. There
may be increased tissue turgor, distention of superficial veins, and the appearance of
prominent venous collaterals. In some patients, deoxygenated hemoglobin in stagnant
veins imparts a cyanotic hue to the limb, a condition called phlegmasia cerulea dolens.
In markedly edematous legs, the interstitial tissue pressure may exceed the capillary
perfusion pressure, causing pallor, a condition designated phlegmasia alba dolens.

The diagnosis of DVT7 of the calf is often difficult to make at the bedside. This is so
because only one of multiple veins may be involved, allowing adequate venous return
through the remaining patent vessels. The most common complaint is calf pain.
Examination may reveal posterior calf tenderness, warmth, increased tissue turgor or
modest swelling, and, rarely, a cord. Increased resistance or pain during dorsiflexion of
the foot (Homans' sign) is an unreliable diagnostic sign.

DVT8 occurs less frequently in the upper extremity than in the lower extremity, but the
incidence is increasing because of greater utilization of indwelling central venous
catheters. The clinical features and complications are similar to those described for the
leg.

Diagnosis D-Dimer, a degradation product of cross-linked fibrin, is often elevated in

patients with venous thrombosis. It is a sensitive, but not specific, test for venous
thrombosis. The noninvasive test used most often to diagnose DVT9 is duplex venous
ultrasonography (B-mode, i.e., two-dimensional, imaging, and pulse-wave Doppler
interrogation). By imaging the deep veins, thrombus can be detected either by direct
visualization or by inference when the vein does not collapse on compressive
maneuvers. The Doppler ultrasound measures the velocity of blood flow in veins. This
velocity is normally affected by respiration and by manual compression of the foot or
calf. Flow abnormalities occur when deep venous obstruction is present. The sensitivity
of duplex venous ultrasonography approaches 95% for proximal DVT and 75% for
symptomatic calf vein thrombosis.

Magnetic resonance imaging (MRI) is another noninvasive means to detect DVT10. Its
diagnostic accuracy for assessing proximal DVT is similar to that of duplex
ultrasonography. It is useful in patients with suspected thrombosis of the superior and
inferior venae cavae or pelvic veins.

DVT11 can also be diagnosed by venography. Contrast medium is injected into a

superficial vein of the foot and directed to the deep system by the application of
tourniquets. The presence of a filling defect or absence of filling of the deep veins is
required to make the diagnosis.

DVT12 must be differentiated from a variety of disorders that cause unilateral leg pain or
swelling, including muscle rupture, trauma, or hemorrhage; a ruptured popliteal cyst;
and lymphedema. It may be difficult to distinguish swelling caused by the postphlebitic
syndrome from that due to acute recurrent DVT. Leg pain may also result from nerve
compression, arthritis, tendinitis, fractures, and arterial occlusive disorders. A careful
history and physical examination can usually determine the cause of these symptoms.

TREATMENT
Anticoagulants (See also Chap. 244) Prevention of pulmonary embolism is the most
important reason for treating patients with DVT13, since in the early stages the thrombus
may be loose and poorly adherent to the vessel wall. Patients should be placed in bed,
and the affected extremity should be elevated above the level of the heart until the
edema and tenderness subside. Anticoagulants prevent thrombus propagation and
allow the endogenous lytic system to operate. Initial therapy should include either
unfractionated heparin or low-molecular-weight heparin. Unfractionated heparin should
be administered intravenously as an initial bolus of 7500 to 10,000 IU, followed by a
continuous infusion of 1000 to 1500 IU/h. The rate of the heparin infusion should be
adjusted so that the activated partial thromboplastin time (aPTT) is approximately twice
the control value. Subcutaneous injection of heparin has been used as an alternative
form of therapy. In <5% of patients, heparin therapy may cause thrombocytopenia
(heparin-induced thrombocytopenia, HIT). Infrequently, these patients develop arterial
thrombosis and ischemia.

Low-molecular-weight (4000 to 6000 Da) heparins are as effective as or better than

conventional, unfractionated heparin in preventing extension or recurrence of venous
thrombosis. Depending on the specific preparation, low-molecular-weight heparin is
administered subcutaneously, in fixed doses, once or twice daily; for example, the dose
of enoxaparin is 1 mg/kg subcutaneously bid. The incidence of thrombocytopenia is less
with low-molecular-weight heparin than with conventional preparations. A direct
thrombin inhibitor, such as lepirudin or argatroban, may be used as initial anticoagulant
therapy for patients in whom heparin is contraindicated because of HIT. Warfarin is
administered during the first week of treatment with heparin and may be started as early
as the first day of heparin treatment if the aPTT is therapeutic. It is important to overlap
heparin treatment with oral anticoagulant therapy for at least 4 to 5 days because the
full anticoagulant effect of warfarin is delayed. The dose of warfarin should be adjusted
to maintain the prothrombin time at an international normalized ratio (INR) of 2.0 to 3.0.

Anticoagulant treatment is indicated for patients with proximal DVT14, since pulmonary
embolism may occur in ~50% of untreated individuals. The use of anticoagulants for
isolated DVT of the calf is controversial. However, approximately 20 to 30% of calf
thrombi propagate to the thigh, thereby increasing the risk of pulmonary embolism. The
overall incidence of pulmonary embolism in patients presenting initially with deep calf
vein thrombosis is 5 to 20%. Also, isolated calf vein thrombosis has been identified as a
cause of embolic stroke via a patent foramen ovale.

Therefore, patients with calf vein thrombosis should either receive anticoagulants or be
followed with serial noninvasive tests to determine whether proximal propagation has
occurred. Anticoagulant treatment should be continued for at least 3 to 6 months for
patients with acute idiopathic DVT and for those with a temporary risk factor for venous
thrombosis to decrease the chance of recurrence. In a recent study of patients with
idiopathic venous thromboembolism, long-term management with low-intensity warfarin
using a targeted INR15 of 1.5 to 2.0, following at least 3 months of therapy with full-dose
anticoagulation, reduced the risk of recurrent DVT and pulmonary embolism. The
duration of treatment is indefinite for patients with recurrent DVT and for those in whom
associated causes, such as malignancy or hypercoagulability, have not been eliminated.
If treatment with anticoagulants is contraindicated because of a bleeding diathesis or
risk of hemorrhage, protection from pulmonary embolism can be achieved by
mechanically interrupting the flow of blood through the inferior vena cava. Inferior vena
cava plication generally has been replaced by percutaneous insertion of a filter.

Thrombolytics Thrombolytic drugs such as streptokinase, urokinase, and tPA4 may

also be used, but there is no evidence that thrombolytic therapy is more effective than
anticoagulants in preventing pulmonary embolism. However, early administration of
thrombolytic drugs may accelerate clot lysis, preserve venous valves, and decrease the
potential for developing postphlebitic syndrome.

Prophylaxis Prophylaxis should be considered in clinical situations where the risk of

DVT16 is high. Low-dose unfractionated heparin (5000 units 2 h prior to surgery and
then 5000 units every 8 to 12 h postoperatively), warfarin, and external pneumatic
compression are all useful. Low-dose heparin reduces the risk of DVT associated with
thoracic and abdominal surgery and with prolonged bed rest. Low-molecular-weight
heparins have been shown to prevent DVT in patients undergoing general or orthopedic
surgery and in acutely ill medical patients. They are said to be more effective than
conventional heparin and to cause an equal or lower incidence of bleeding. Danaparoid,
a low-molecular-weight heparinoid, may be used for prophylaxis in patients undergoing
hip surgery. Fondaparinux, a synthetic pentasaccharide capable of catalysing
antithrombin-mediated inhibition of factor Xa, may be used for prophylaxis in patients
undergoing major orthopedic surgery. Warfarin in a dose that yields a prothrombin time
equivalent to an INR17 of 2.0 to 3.0 is effective in preventing DVT associated with bone
fractures and orthopedic surgery. Warfarin is started the night before surgery and
continued throughout the convalescent period. External pneumatic compression devices
applied to the legs are used to prevent DVT when even low doses of heparin or warfarin
might cause serious bleeding, as during neurosurgery or transurethral resection of the
prostate.

SUPERFICIAL VEIN THROMBOSIS

Thrombosis of the greater or lesser saphenous veins or their tributaries — i.e.,

superficial vein thrombosis — does not result in pulmonary embolism. It is associated
with intravenous catheters and infusions, occurs in varicose veins, and may develop in
association with DVT18. Migrating superficial vein thrombosis is often a marker for a
carcinoma and may also occur in patients with vasculitides, such as thromboangiitis
obliterans. The clinical features of superficial vein thrombosis are easily distinguished
from those of DVT. Patients complain of pain localized to the site of the thrombus.
Examination reveals a reddened, warm, and tender cord extending along a superficial
vein. The surrounding area may be red and edematous.

TREATMENT
Treatment is primarily supportive. Initially, patients can be placed at bed rest with leg
elevation and application of warm compresses. Nonsteroidal anti-inflammatory drugs
may provide analgesia but may also obscure clinical evidence of thrombus propagation.
If a thrombosis of the greater saphenous vein develops in the thigh and extends toward
the saphenofemoral vein junction, it is reasonable to consider anticoagulant therapy to
prevent extension of the thrombus into the deep system and a possible pulmonary