Diagnostic management of venous thromboembolism

Signs and symptoms of acute venous thromboembolism (VTE) are notoriously nonspecific. Therefore, diagnostic management algorithms have been developed, consisting of a clinical decision rule (CDR), D-dimer testing and imaging tests, that allow safe diagnostic management and the exclusion of VTE in clinical practice. However, several challenges still remain: adherence to the diagnostic algorithms, accurate diagnosis of recurrent VTE, reducing the radiation exposure associated with computed tomography pulmonary angiography for suspected pulmonary embolism, and accurate diagnosis of thrombosis at unusual places.

Our group has been involved in performing exploratory studies to evaluate potential improvements of new diagnostic tests/algorithms, as well as performing outcome studies to definitely establishing the safety and efficacy of these new tests/algorithms. For example, the Titan study program aims to evaluate the diagnostic accuracy of a novel MR technique referred to as ‘direct thrombus imaging’ (DTI). With this technique, the product of hemoglobin oxidation to methemoglobin, which has paramagnetic properties resulting from its five unpaired electrons, is visualized due to shortening of the T1 relaxation time. MRDTI does not require intravenous contrast medium and takes only a few minutes to perform. MRDTI has the unique possibility to clearly visualize fresh blood clots and to differentiate between acute and chronic thrombosis. The afore mentioned Titan study program includes several studies that focus on the accuracy of DVT for diagnosing recurrent DVT of the leg, DVT of the upper extremity, abdominal vein thrombosis and cerebral vein thrombosis.

Three relevant publications of our group (with collaborators) within this theme are:
1. van der Hulle T, Cheung WY, Kooij S, Beenen LFM, van Bemmel T, van Es J, Faber LM, Hazelaar GM, Heringhaus C, Hofstee H, Hovens MMC, Kaasjager KAH, van Klink RCJ, Kruip MJHA, Loeffen RF, Mairuhu ATA, Middeldorp S, Nijkeuter M, van der Pol LM, Schol-Gelok S, Ten Wolde M, Klok FA, Huisman MV; YEARS study group. Simplified diagnostic management of suspected pulmonary embolism (the YEARS study): a prospective, multicentre, cohort study. Lancet 2017;390:289-297
2. Tan M, Mol GC, van Rooden CJ, Klok FA, Westerbeek RE, Iglesias Del Sol A, van de Ree MA, de Roos A, Huisman MV. Magnetic resonance direct thrombus imaging differentiates acute recurrent ipsilateral deep vein thrombosis from residual thrombosis. Blood 2014;124:623-627
3. van Es N, van der Hulle T, van Es J, den Exter PL, Douma RA, Goekoop RJ, Mos IC, Galipienzo J, Kamphuisen PW, Huisman MV, Klok FA, Büller HR, Bossuyt PM. Wells Rule and d-Dimer Testing to Rule Out Pulmonary Embolism: A Systematic Review and Individual-Patient Data Meta-analysis. Ann Intern Med 2016;165:253-261