Venous Disease

Michael A. Ricci, MD, RVT

Venous Thrombosis:
Thrombosis begins in the valve cusps or at sites of direct venous injury with the accumulation of platelets. Activation of the coagulation cascade occurs as factor XII (Hageman Factor) contacts any surface other than endothelium, such as the aggregated platelets. Ultimately, fibrin which stabilizes the platelet clump. If natural fibrinolytic mechanisms, including Antithrombin III (which opposes the activity of factors IX, X, XI, XII), are unable to reverse this process, platelets and fibrin continue to accumulate, eventually obstructing the venous channel and propagating clot in both directions from the site of origin.1,2

The factors that predispose to venous thrombosis first described by Virchow3 in 1856 are still useful today: stasis, hypercoagulability, and endothelial injury.

Venous stasis is enhanced by immobility or venous obstruction and contributes to thrombosis by preventing dilution and washout of activated clotting factors.4 Blood pools in the venous lakes of the calf during bed rest, promoting the development of venous thrombosis during and after surgery or trauma.4,5

Hypercoagulability occurs after almost any surgical procedure, trauma, or burns, as well as with widespread malignancies.2,4-7 Conditions such as polycythemia vera, which produces thrombocytosis and erythrocytosis, or paroxysmal nocturnal hemoglobinuria predispose to thrombosis.7 Systemic lupus erythematosus may produce circulating immune complexes (the lupus anticoagulant) which injure endothelial cells which paradoxically elevates the activated partial thromboplastin time while predisposing the patient to venous thrombosis.2 Drugs, such as estrogens, may cause venous thrombosis by promoting venous dilation and status in addition to lowering fibrinolytic activity and Antithrombin III levels.2,7 Inherited hypercoagulable states are produced by a deficiency of Antithrombin III,2,8 protein C (which inactivates factors V and VIII),2,8,9 Protein S (a cofactor for Protein C activity),2 or fibrinolytic proteins.2

Finally, direct injury to the veins is a less frequent contributor to thrombosis but may follow venous trauma,4 venography,10 or even thermal injury from curing methyl methacrylate from total joint replacement.11 Clinical factors which place patient at risk for thromboembolism are listed in below.

Clinical Risk Factors for Venous Thromboembolism
Increasing Age
Surgery (especially joint replacements)
Trauma/Major Burns
Paralysis/Immobilization/Bed Rest
Malignancy
Prior Thromboembolism
Pregnancy
Obesity
Nephrotic Syndrome
Oral Contraceptives/Estrogens
Hyperviscosity States (polycythemia vera, myeloproliferative disorders, paroxysmal nocturnal hemoglobinuria)
Primary Hypercoagulable states (Antithrombin III deficiency, protein C deficiency, protein S deficiency, hypofibrinogenemia, defective fibrinolytic states)

Earliest observations suggested that deep thrombi originate in the deep muscular veins of the calf. A study of surgical patients found the most venous thrombi arise in the calf and 20% of these propagate into the popliteal and femoral veins.12 An autopsy study by Sevitt and Gallagher4, however, showed six sites where thrombi may form primarily: intramuscular veins of the calf, posterior tibial veins, deep femoral veins, common femoral veins, iliac veins, and popliteal veins.

Thrombi may undergo lysis, organize and recanalize, or embolize to the lungs. While pulmonary emboli may arise from thrombi at any level in the venous system, the most serious threat is from thrombi above the popliteal vein.2,6 Large pulmonary emboli may cause sudden death, especially if more than a third of pulmonary arterial flow is obstructed.13 Large emboli produce a failure of oxygenation and acute right ventricular strain as well as bronchospasm.1 Smaller emboli may cause pulmonary infarction,1 and over the long term, subacute or occult emboli may cause pulmonary hypertension.14

Chronic Venous Insufficiency:
Deep venous thrombosis leads to valvular damage and, ultimately, venous hypertension. This leads to chronic tissue edema and an increase in subcutaneous and skin capillaries.1 Over time, an increase in capillary permeability to fibrinogen develops, leading to the accumulation of fibrin in the perivascular space.1 This reduces the diffusion capability of oxygen, producing chromic tissue injury, all of which is manifested clinically as the typical "woody edema". Further progression of this process or impaired heading of minor wounds leads to venous ulceration.

DIAGNOSIS

Contrast Venography:
Venography remains the gold standard for the diagnosis of venous thrombosis.14 The most reliable sign of thrombosis is a constant filling defect or so called "railroad track sign" with contrast outlining the clot. Non-filling of a vein or the entire deep system, diversion of flow, or collateral veins are not diagnostic alone, but in the proper clinical setting are presumptive evidence of acute venous thrombosis.14 Even technically superior studies, however, may not fill the iliac veins in 18% of the time11 so some caution in interpretation may be necessary.

The technique of contrast venography was described in 192317 and although a number of modifications have been introduced, essential elements still include dye injection into the veins of the foot with the patient on a tilt table. Use of new digital imaging techniques in conjunction with conventional films may provide complete venous imaging with lower dye loads.

Complications of venography are related to the contrast media. The most immediate and serious complication is anaphylaxis, secondary to the contrast injection, which is fortunately a rare event. Extravasation of contrast may cause pain. The contrast agent may also induce a thrombosis in up to 5% of cases.14 Precautions such as flushing of the veins with saline and early ambulation probably reduce this risk.

Though many of the non-invasive techniques below make contrast venography unnecessary, it still has a role when other methods are equivocal or insufficient or in complicated clinical situations. Venography remains the best technique to define the venous anatomy.

Isotope Studies:
Fibrinogen labeled with iodine-125 (125I) has been used as a minimally invasive technique for the demonstration of thrombi. Labeled fibrinogen is trapped in organizing clot. When the fibrinogen is labeled with a radioactive material, it can be localized with the use of equipment to measure radioactivity over the legs and pelvis. It is necessary to block the thyroid gland with sodium iodide approximately 24 hours before the test. This test may be the most sensitive available, particularly for detecting thrombi at the calf level. Accuracy has been found to be greater than 90% 14,18, but in the thigh this may be lower. The test may be obscured by surgery, inflammation, or hematoma in the limb since it cannot differentiate fibrinogen deposition with these conditions or with deep venous thrombosis. Although minimally invasive, this test carries the risk of transmitting infections via the human fibrinogen used for labeling.18

Plethysmography:
These techniques measure changes in the volume of the limbs under normal circumstances and with thrombotic obstruction of the veins. Two techniques, impedance plethysmography (IPG) and phleborrheography (PRG), have proven the most reliable. IPG is based upon Ohm's law, V=IR, so that when an undetectable current is placed across the limb, the voltage recorded depends upon the electrical impedance, which varies with limb volume. PRG relies on these same principles to detect volume changes when the distal limb is compressed.

Plethysmographic techniques are most sensitive in detecting thrombi within the proximal venous system. Calf-vein thrombi, small non-occlusive thrombi, or older thrombi may yield false-negative results. Reliability of both IPG and PRG in the proximal segment, where the risk is greatest, is over 90%.4, 14,19,20

Because these tests are reliable and non-invasive, their use as screening tests in post-operative patients has been suggested.4,14,20 In addition, in the absence of conditions that may produce a false-negative or false-positive exam, IPG or PRG may be sufficient to exclude or confirm the diagnosis of deep venous thrombosis.

Duplex Ultrasonography:
Duplex ultrasound scanning has supplanted venography as the primary diagnostic test to diagnose deep venous thrombosis in most cases.21 The duplex scan provides both anatomic and physiologic information by providing a gray-scale image of the venous system, Doppler ultrasound evaluation of flow, and recently, color images of flow patterns.

This test is based upon the Doppler principle; an emitted frequency reflected off a moving object returns at a different frequency. That change in frequency is the "Doppler shift". Thus, ultrasound reflected from stationery tissues produces a static image. Moving red blood cells produce a shift that may be interpreted as an audible or printed signal. If a multitude of frequencies are detected and a color is assigned to the direction of flow, a dynamic color image of flow patterns within the vein may be detected.

Deep venous thrombosis may be detected by visualization of clot within the veins, inability to manually compress (with the ultrasound probe) a vein because of clot, or abnormalities in the Doppler flow patterns or color image.21 Although this test has been shown to be most reliable in the proximal venous segments with sensitivity and specificity greater than 90%,22 data is emerging to indicate it is also reliable in the calf23 and iliac veins.24 The safety, versatility, and reliability of this non-invasive test have made it the new "gold standard" in diagnosing venous thrombosis.

Duplex Ultrasound Technique:
The patient should be positioned with the head elevated (about 10-20° incline) and feet dependent so that the veins are filled. The knee should be flexed slightly and the leg externally rotated. This position allows scanning of the large veins of the abdomen, the common femoral vein, the deep femoral vein, the superficial femoral vein to the level of the adductor canal, the popliteal vein below the knee, the posterior tibial veins, the peroneal veins, and the greater saphenous vein. With the patient supine and the leg in neutral position, the anterior tibial veins may be imaged. Adequate visualization of the popliteal vein usually requires the patient to be in the prone position or lateral decubitus position. The lesser saphenous vein may also be imaged from that position as well as the peroneal or posterior tibial veins.

Most of the exam can be done with a 5 MHz probe. A deep abdominal probe (3.5 MHz) will be necessary to visualize the inferior vena cava and iliac veins while a 7.5 MHz probe may be needed for the superficial greater and lesser saphenous veins. Body habitus may affect the choice of probes since an obese patient may be better visualized with the deep probe or a very thin person with the superficial probe.

A thorough knowledge of the venous and arterial anatomy is mandatory. Each vein is adjacent to its corresponding artery, which may help in identification. Our scanning protocol begins in the groin, without color, to transversely image the common femoral, deep femoral, and proximal superficial femoral veins as well as the saphenofemoral junction. Each vein is compressed at intervals along its course. Each vein is also interrogated with the Doppler ultrasound and/or color flow as well. The Doppler or color flow pattern should normally detect spontaneous, phasic flow that is augmented with distal compression as well as with release of proximal compression or the Valsalva maneuver. This sequence is repeated as the remainder of the superficial femoral vein and the greater saphenous vein in the thigh is examined. Next in sequence the popliteal vein below the knee is scanned followed by medial scanning the length of the calf of the peroneal (deep), posterior tibial (more superficial), and greater saphenous (most superficial) veins. The leg is straightened for interrogation of the anterior tibial veins which, proximally in the calf are deep, but course to a more superficial position at the ankle. Next, we return to the groin to follow the femoral vein proximally into the external iliac and common iliac veins. Finally, the inferior vena cava, adjacent to the aorta, is identified and interrogated. Although the iliac veins cannot be compressed, occasionally, in a very thin person, it is possible to compress the vena cava. After repositioning the patient, as described above, the popliteal and lesser saphenous veins are imaged.

Interpretation:
The normal vein should demonstrate the following characteristics:25
Slightly larger in size than the adjacent artery when the limb is dependent
Size of vein increases with Valsalva or proximal compression
Completely compressible

Doppler ultrasound/color flow characteristics:
Spontaneous flow
Phasic flow (with respiration)
Flow augments with distal compression
Flow augments with release of Valsalva or proximal compression

Thrombus is indicated by:
Inability to compress the vein
Echogenic material within the vein lumen
Dilated vein
Absent or decreased spontaneous flow
Loss of phasicity
Absent or decreased augmentation

It may be possible to estimate the age of the thrombus based upon its ultrasound characteristics.25 Acute thrombus is minimally echogenic with smooth borders and may be poorly attached with a free-floating tail. As thrombus ages, echogenicity increases and the clot becomes firmly attached to the vein wall. The thrombus is firmer. The vein is likely to be contracted but may show flow through irregular recanalized channels.

Pitfalls:
The following structures may be confused with venous thrombosis:25

Lymph nodes Tumor
Baker's cyst Valves
Hematoma Intravenous catheters
Abscess
Bowel with fecal material

REFERENCES

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