Prevalence and predictors of alternative diagnoses on whole-leg ultrasound negative for acute deep venous thrombosis

Acute deep venous thrombosis (DVT) is a common condition for which patients seek emergency medical care and is associated with pulmonary embolism as a potentially life-threatening complication. Therefore, accurate diagnosis and prompt initiation of anticoagulant therapy is important to reduce morbidity [1]. Clinical signs and symptoms of DVT are often vague [2] and laboratory D-dimer tests, routinely used for DVT screening, tend to have low specificity [3]. Duplex ultrasound of the lower extremity has therefore become the standard radiological screening test for patients with suspected acute DVT [4].

Some centers choose to perform a limited compression ultrasound examination as the initial test focusing primarily on the femoral and popliteal veins [5‐8]. We prefer to perform a whole-leg ultrasound in all patients with suspected acute DVT in our institution, conforming to current multidisciplinary guidelines [4]. The major advantage of this approach, in addition to detection of isolated calf DVT, is that it allows to identify alternative diagnoses which may have caused the patient’s leg symptoms, thereby mimicking acute DVT [9‐12].

In most cohort studies, the majority of focused ultrasound examinations for DVT in patients with suspected acute DVT are negative (56 to 77%) [13‐15]. However, most of these patients had signs or symptoms that led to the clinical suspicion of acute DVT. For both health care providers and patients, it can be unsatisfactory to rule out DVT and discharge the patient without identifying a cause for the patient’s symptoms. Many alternative diagnoses such as chronic venous insufficiency (CVI) or soft tissue inflammation require specific treatment and it would be prudent to not miss these diagnoses during the initial work-up. Hence, evaluation for alternative diagnoses using whole-leg ultrasound in patients with negative acute DVT scans may enhance the overall quality of patient care as well as patients’ and health care providers’ satisfaction.

Therefore, we performed this study to investigate the prevalence, spectrum and predictors of alternative diagnosis explaining leg symptoms among patients evaluated with whole-leg ultrasound for suspected DVT.

In this cohort study of patients negative for acute DVT on whole-leg ultrasound, alternative diagnoses were found in two thirds of the patients with CVI being the most common alternative diagnosis. Patients with alternative diagnoses were older, more likely to present with leg swelling, difference in leg circumference and redness than patients without an identifiable alternative diagnosis. Independent predictors of finding alternative diagnoses on whole-leg ultrasound were older age, leg swelling and a past history of DVT.

Few prior studies have investigated alternative diagnoses in patients with suspected acute DVT found on whole-leg ultrasound examination [9, 16, 17]. In these studies, alternative diagnoses were observed less often with whole-leg ultrasound, (11% to 31% of all patients with suspected DVT) [9, 16, 17] as compared to our study (44%). In all of these studies, ultrasound scans were either performed by ultrasound technicians [16]/sonographers [17], or by vascular technologists and interpreted by vascular surgeons [9]. This is in contrast to our study, here board-certified radiologists with subspecialisation in vascular and interventional radiology. performed or directly supervised the ultrasound examinations. It can therefore be speculated that the higher prevalence in our study may in part be due to radiologist-performed vs. non radiologist-performed ultrasound, since it is known that duplex ultrasound is highly operator dependent [18, 19]. The most common alternative diagnoses reported in these studies included chronic venous insufficiency [9], lymphadenopathy [16] and old thrombosis/post-thrombotic changes [17] similar to our study.

We assessed predictors for finding an alternative diagnosis on whole-leg ultrasound in patients suspected but negative for acute DVT. In a study to identify the risk factors for the common alternative diagnoses in patients with clinically suspected DVT (CVI, erysipelas, muscle rupture/hematoma and superficial venous thrombosis) [20] Cate Hoek et al. found that patients with CVI reported more often swelling of the entire leg having an insidious onset, as compared to patients with a confirmed diagnosis of acute DVT. Limb redness was seen as a distinctive feature in patients with erysipelas. Patients with muscle rupture/hematoma had neither swelling nor redness. Furthermore, patients with superficial venous thrombosis had tenderness on palpation of the offending vein [20]. However, all these four alternative diagnoses were based on clinical evaluation in a primary care setting and not based on whole-leg ultrasound findings as in our study [20].

In our analysis, older age, leg swelling and previous DVT were independent predictors of finding alternative diagnoses in patients without acute DVT on whole-leg ultrasound. A frequent complication of DVT includes the post-thrombotic syndrome (PTS) with a relatively high number of patients between 20 to 50% within 2 years of DVT diagnosis [21, 22]. Clinical manifestations of PTS typically include limb pain, heaviness, edema and pruritus [23]. PTS is a form of CVI that occurs due to chronic venous obstruction and damaged vein valves [21, 22]. Duplex ultrasound is the first imaging test of choice to evaluate for signs of CVI and post-thrombotic changes [24]. This might explain, why a past history of DVT was identified as risk factor for finding an alternative diagnosis on whole-leg ultrasound.

Since alternative diagnoses are relatively common in patients having a suspicion of acute DVT and these alternative diagnoses have important therapeutic consequences [10], focused sonographic evaluation of the venous system alone may not be sufficient in all patients with suspected acute DVT presenting with lower extremity symptoms. Useche et al. [10] state that in addition to whole-leg sonography in supine position, comparison of both extremities, performing specific maneuvers to elicit symptoms, as well as observing changes due to articular movement and switching to a standing position during the ultrasound examination might also be helpful. However, resources and time required may be limited in most emergency departments [16]. Nevertheless, the effort to establish an alternative diagnosis, when DVT is ruled out, seems particularly advisable in patients, who meet the following criteria: older age, leg swelling and previous history of DVT, which we identified to be independent predictors in our study. It should be kept in mind that patient compliance with follow-up ultrasound examinations after initial ultrasound negative for DVT seems to be extremely low [25], which also advocates the importance of performing a comprehensive initial ultrasound evaluation. As a practical implication of our study, we suggest to add targeted ultrasound of symptomatic areas if no DVT is found on standard thigh-to-ankle venous doppler ultrasound examination; particularly in older patients who present with leg swelling and a previous history of DVT.

This study has some limitations, which include its retrospective single-center nature. Symptomatic patients who presented to a university hospital were included in our analysis. This patient population may be different as compared to patients seen by primary care physicians. No external reference standard was available to confirm the findings. A more comprehensive prospective study is needed to determine the impact of alternative findings on subsequent diagnostic algorithm in patients and the benefits including costs in patient management.

In summary, we found that alternative findings explaining leg symptoms can be detected on whole-leg ultrasound in two thirds of patients negative for acute DVT. Therefore, our study supports performing a detailed whole-leg ultrasound evaluation beyond the venous system (including targeted ultrasound of symptomatic areas) when negative for acute DVT. This may be particularly relevant in older patients, who present with leg swelling and who have a previous history of DVT, which were identified as independent predictors in our patient cohort.