21 – Is there a role for lower extremity venograms for the diagnosis of lower extremity DVT?

21 – Is there a role for lower extremity venograms for the diagnosis of lower extremity DVT?

Tomasz Urbanek.

Response/Recommendation 1: The use of lower extremity venograms for routine diagnosis of lower extremity deep venous thrombosis (DVT) is not recommended. For patients with suspicion of lower leg DVT requiring imaging, venous ultrasound (VUS) is recommended as the first diagnostic modality.

Strength of Recommendation: Strong.

Response/Recommendation 2: In patients with suspicion of iliac or vena cava thrombosis, as well as inconclusive or impossible to perform VUS, computer tomography venography (CTV) or magnetic resonance venography (MRV) should be performed, based on availability and center experience.

Strength of Recommendation: Moderate.

Response/Recommendation 3: In the patients with strong suspicion for lower extremity DVT and inconclusive or impossible to perform VUS, examination of the veins below the inguinal ligament should be done with CTV, MRV or contrast phlebography.

Strength of Recommendation: Moderate.

Response/Recommendation 4: In clinical trials with a study endpoint including the presence of lower leg asymptomatic DVT, the use of contrast venography may be performed as these are required by the regulatory bodies.

Strength of Recommendation: Moderate.

Rationale: In the current DVT diagnostic algorithm, the initial imaging method of patients with high clinical suspicion for lower leg DVT remains the VUS1–3. High accuracy of the sonographic examination-based strategy was confirmed in several studies and meta-analyses as well as emphasized in several guideline documents1–10.

Historically, traditional contrast venography, based on direct lower leg intravenous contrast injection, was used as the first objective imaging modality and for many years had been considered the “gold standard” for diagnosis of DVT11,12. Before the modern VUS era, due to limitations concerning other available diagnostic methods, including plethysmography, thermography, continuous-wave Doppler examination or isotopic studies, phlebography became another standard diagnostic imaging method to confirm DVT13–18. The rates of diagnosed DVT by bilateral venography in orthopaedic surgery studies became the reference values for further research on DVT prophylaxis efficacy in orthopaedic surgery. Chen et at., reported a 21.9% DVT incidence (with proximal DVT rate – 4%) after arthroscopic posterior cruciate ligament reconstruction19. In a study by Kim et al., 26% of the bilateral venograms turned out to be positive for DVT in patients after total hip arthroplasty (THA)20. Clarke et al., in a venography-based study dedicated to hip and knee arthroplasty patients not receiving thromboprophylaxis, found a 32% DVT rate after THA (proximal DVT – 16%) and 66% DVT rate after total knee replacement (TKA) (proximal DVT – 16%)21. A systematic review of the prospective clinical studies on DVT prevalence, with the use of contrast venography, in patients undergoing elective hip or knee surgery documented the presence of DVT in the operated leg in 16.7% of THA patients and in 33.8% of TKA patients. At the same time, DVT presence in the contralateral leg was noted in 4-5% of the cases22.

Contrast phlebography, together with venous thromboembolism (VTE) symptom evaluation, became another standard efficacy outcome evaluation method in a number of clinical trials including thromboprophylaxis trials in major orthopaedic surgery, as well as other specialties23–26. The common use of contrast venography in VTE prophylaxis trials reflects not only its accuracy in diagnosing DVT in the symptomatic patients, but also the possibility of diagnosing the presence of asymptomatic DVT27,28.

In contrast to diagnosis oriented on the symptomatic leg, implementation of bilateral phlebography allows one to evaluate the presence of asymptomatic thrombosis in both extremities. Besides high sensitivity, including in the diagnosis of asymptomatic DVT cases, the advantages of direct contrast venography include the possibility of visualizing calf vein DVT as well as non-occlusive thrombotic changes29–33.

Several studies, using contrast venography as the reference method, confirmed the efficacy of VUS in the diagnosis of DVT. However, the reported high sensitivity of the VUS shown in the femoro-popliteal segment decreases in below the knee veins34–38. It should be mentioned that the presence of symptomatic as well as asymptomatic DVT, including below the knee and non-occlusive DVT, frequently became the endpoint for clinical trials, especially in trials dedicated to VTE prophylaxis. Barnes et al., in a study based on combined B-mode/duplex Doppler scanning and venography, compared the results of routine postoperative screening for DVT in 158 THA patients. With a 12% incidence of proximal DVT (and total DVT rate of 30% including calf vein DVT), the duplex scan had a sensitivity of 79%, specificity of 98%, and accuracy of 97%, in relation to venography as the reference method39.

Despite the fact that phlebography was considered to be the “gold standard” for diagnosis of DVT, the possibility of inadequate results (evaluation) when using this technique remains significant, reaching as high as 6 to 20%40–43. Important points of concern include limited intra- and inter-observer agreement on venography results, as well as the lack of proper filling of the entire lower leg venous system (especially when injecting contrast into the foot vein for proximal deep vein segment visualization)43–49.

The technical progress of the ultrasound (US) technology as well as an improvement in diagnostic protocols based on compression US as well as duplex Doppler examination increased sensitivity and specificity of the sonographic examination in DVT diagnosis. Simultaneously, the invasiveness of phlebography related to the contrast injection as well as significant exposure to radiation, together with an improvement in the alternative methods nowadays limits the use of phlebography in daily practice. Besides the adverse effects related to phlebography performance, potential contraindications should also be mentioned, including contrast allergies as well as potential for renal impairment50–52.

Taking into account the clinical practice as well as method limitations, standard venography is now rarely used in daily clinical practice and its practical implementation in DVT patient management concerns mostly patients undergoing acute DVT catheter-directed thrombolysis or endovascular revascularization as well as chronic post-thrombotic venous obstruction treatment. In cases of proximal (including iliac) venous thrombosis suspicion and non-conclusive results of the US examination, CTV or MRV imaging is currently preferred to contrast phlebography53. The use of bilateral direct contrast venography remains an interesting option in clinical trials evaluating symptomatic and asymptomatic lower leg DVT.

CTV is efficacious in the diagnosis of proximal lower leg DVT54. CTV also more clearly demonstrates thrombus extension into the veins above the inguinal ligament or inferior vena cava than conventional contrast venography55,56. The costs of CTV examination, as well as its availability together with the invasiveness of the CTV study (contrast injection, radiation exposure) limit its use as a diagnostic measure to cases with diagnostic problems as well as inconclusive results of previous imaging studies, especially if proximal DVT is suspected. The use of CTV as the screening method for lower leg DVT in clinical studies on thromboprophylaxis is still rather rare57.

An important clinical subject related to CTV as a diagnostic method is the possibility of simultaneous lower leg CTV performance in patients undergoing computer tomography pulmonary artery angiography (CTPAA) because of pulmonary embolism (PE) suspicion. As suggested in several studies dedicated to this topic, CTV simultaneously performed with CTPAA offers limited value for detecting DVT and should not be performed as a routine screening test58.

Looking for less invasive and simplified diagnostic options of the venous system in patients with suspected PE undergoing CTPAA, the use of lower leg sonographic examination instead of the CTV was also proposed. In the Prospective Investigation of Pulmonary Embolism Diagnosis II (PIOPED II) study, CTV performed after CTPAA showed that lower extremity imaging detects about 7% more patients requiring anticoagulation than CTPAA alone59. In 711 patients of the same study (PIOPED II) the accuracy of the CTV was compared with compression US. According to results, there was 95.5% concordance between CTV and sonography for DVT diagnosis or exclusion, and the sensitivity and specificity of combined computed tomographic angiography (CTA) and CTV were equivalent to those of combined CTA and sonography59.

Despite promising results, the role of MRV in lower leg DVT diagnosis is still under evaluation. According to a meta-analysis, similar sensitivity and specificity of MRV and VUS is suggested (especially in the femoropopliteal segment)60. Due to the heterogenicity of the studies, as well as differences in magnetic resonance imaging (MRI) diagnostic protocols, the promising results of the available studies have to be repeated and confirmed in a large number of patients and diagnostic centers.  Another option is an identification of DVT by means of direct thrombus imaging61. MRI can also be used to assess the characteristic of the thrombosis to help differentiate between acute, subacute and chronic changes62. Due to the costs as well as method availability, there is, for now, no argument supporting the replacement of US with MRV as a first-line imagining modality in the patients with DVT suspicion. As an alternative diagnostic tool, MRV can be considered for patients in whom venous US is not possible to perform or the results are inconclusive63. Similar to CTV, one of the important advantages of the MRV study is the potential for pelvic vein or retroperitoneal vein visualization, which is not always correctly seen and assessed in the VUS examination.


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