Commentary (Lohr): Diagnosis of Venous Thromboembolic Disease in Cancer Patients

This article nicely describes concerns about the underdiagnosis of deep vein thrombosis (DVT) and superficial vein thrombosis in patients with malignancy. The incidence of these conditions in this setting has been demonstrated to be as high as 51% in postmortem studies, as opposed to the clinically recognized 15% rate. The article reinforces the need for better diagnostic tools than are currently available in clinical practice. It also stresses the need for a high clinical suspicion. Duplex ultrasound should be used as a first step, and other modalities listed in the article need to be used when appropriate.

Acute vs Chronic Thrombi

The article discusses the strengths and weaknesses of several different diagnostic tools. Unfortunately, it states that venography can differentiate acute from chronic thrombi, suggesting that it is an adequate diagnostic tool for aging thrombi, but this is not completely true. Contrast venography is not the gold standard in all situations, especially when calf vein thrombi are routinely evaluated in a laboratory, as this technique is notorious for missing calf vein thrombi and generally has difficulty visualizing the calf veins. Venous duplex scanning has a much higher accuracy for aging thrombi.

The ability to differentiate acute and aged thrombosis depends on ultrasound criteria. Acute thrombi are either totally occlusive or free floating with clot retraction or vein distention. The clot tends to be soft and compressible. The surface characteristics are smooth, have faint echogenicity, and are homogeneous. Collaterals and recanalization are absent.

In contrast, chronic thrombi are partially occlusive, stationary, and adherent to the wall. They are characterized by thrombus contraction, and the clots are noncompressible and firm. The surface characteristics may be irregular, brightly echongenic, heterogeneous, and noncompressible. Recanalization may be present as well. Acute and chronic mixed characteristics may be present, with acute features on top of chronic thrombus or with a thrombus that is beginning to age.

Advantages of Duplex Ultrasound

Venography is an invasive test with multiple potential complications, including thrombophlebitis. On the other hand, venous duplex scanning requires significant technical experience, but this method routinely visualizes the superficial veins, which are not visualized on venography. Greater and lesser saphenous superficial vein thrombophlebitis involves the superficial venous system when described on duplex examinations. However, in venographic terminology, the superficial femoral vein is a deep vein, which often misleads and confuses the practitioner. The superficial femoral vein is a tributary to the common femoral vein and is actually part of the deep venous system; it should be treated as a DVT when the diagnosis is established using venographic methods.

The article describes some of the veins that are routinely visualized on upper-extremity scanning but fails to mention several others that are included in most vascular laboratory evaluations done with duplex scanning, such as the antecubital, basilic, radial, ulnar, and cephalic veins. Although compression is not done above the inguinal ligament, there are alternative augmentation techniques-including the Valsalva maneuver and attention to Doppler flow changes- that can help diagnose proximal obstruction.

Calf vein visualization is generally reliable on duplex ultrasound, especially if the veins are routinely visualized on all scans and an experienced registered vascular technologist is performing the study. Color flow in some of the newer scanners has increased the ability to visualize calf veins and the deep central veins as well. Duplex ultrasound is the screening method of choice, especially in the asymptomatic setting, because it is noninvasive, easily repeated, and comfortable for the patient.

I agree with the authors' conclusion that all patients with malignancies should have bilateral lower-extremity scans to limit "warfarin failure" and avoid inappropriate treatment decisions for patients with thrombosis. Previous data showed that of 362 patients with asymptomatic lower extremities, 128 (35%) had DVT. Moreover, clots were found in asymptomatic limbs in an additional 263 patients whose contralateral limb was symptomatic.[1]

Magnetic Resonance Techniques

As used in the article by Gomes and Deitcher, magnetic resonance imaging should actually be magnetic resonance venography (MRV) in most situations. Magnetic resonance venography and angiography are helpful in differentiating extrinsic compressive changes. However, flow voids may be difficult to identify and may be a source of error with magnetic resonance technology.

All patients with an active malignancy should be considered at high risk for DVT, and prophylaxis should be employed. In the authors' Figure 1 flowchart, I would follow a nondiagnostic duplex ultrasound with MRV and then a venogram in cancer patients, or if a pulmonary embolism is suspected, a spiral computed tomography scan. If any of these tests were positive, I would proceed with treatment. Moreover, I would alter Figure 1 to start with a duplex color flow, then move to selected venography or MRV, but would not use venography as a first-line test.

Prophylactic Filters

For the most part, the authors nicely summarize what is in practice; issues such as the use of prophylactic filters in patients with malignancy are beyond the scope of the article. To help with early detection in asymptomatic individuals, an even stronger argument could be made for surveillance in patients with malignancy and hypercoaguable states. The use of prophylactic anticoagulation is more aggressively needed to reduce the incidence of initial or recurrent thrombosis.

Recently, at the Midwestern Vascular Surgical meeting, the University of Michigan presented data regarding thromboembolic events in patients with malignancy. Fifty-two percent of the patients had thromboembolic events present at the time of the cancer diagnosis, and 63% had thromboembolic events associated with new metastatic disease. Recurrent thromboembolic events occurred in 32% of these patients. Quality-oflife issues and prophylactic vena cava filters were debated in considering this patient group with late-stage malignancy.[2]

Conclusions

The exact approach to each patient must be individualized. The availability of technical support and equipment in the clinical setting will determine the exact work-up of each patient. I would also recommend the "Guidelines of the American Venous Forum," found in the Handbook of Venous Disorders, as a further reference for those interested in this subject.[ 3,4] A more complete discussion of decision-making, testing methods, and test limitations is provided in this text.

Financial Disclosure: The author has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

References:

1. Lohr J, Hasselfeld K, Byrne M, et al: Does the asymptomatic limb harbor deep venous thrombosis? Am J Surg 168:184-187, 1991.
2. Lin J, Proctor M, Varma M, et al: Factors associated with recurrent thromboembolic events in patients with malignancy. Midwestern Vascular Surgical Society, 26th Annual Meeting, Program Book, p 62, 2002.
3. Guidelines of the American Venous Forum, in Gloviszki P, Yao J (eds): Handbook of Venous Disorders. London, Chapman & Hall Medical, 1996.
4. Guidelines of the American Venous Forum, in Gloviszki P, Yao J (eds): Handbook of Venous Disorders, 2nd ed. London, Arnold, 2001.