17 – What is the optimal imaging modality for detection of upper and lower extremity DVT for patients undergoing orthopaedic procedures?

17 – What is the optimal imaging modality for detection of upper and lower extremity DVT for patients undergoing orthopaedic procedures?

Graham S. Goh, John J. Corvi, Sabine Eichinger.

Response/Recommendation: The optimal imaging modality for the detection of upper and lower extremity deep venous thrombosis (DVT) is venous compression ultrasonography (CUS).  The choice between proximal leg, whole-leg, and serial CUS should be guided by an assessment of clinical pretest probability.

Strength of Recommendation: Strong.

Rationale: The risk of venous thromboembolism (VTE) in major orthopaedic surgery is among the highest of all surgical specialties (4.3% approximated baseline risk of symptomatic VTE without prophylaxis for total hip or knee arthroplasty, or hip fracture surgery).  Consequently, VTE is a major cause of morbidity, mortality, and increased healthcare costs following orthopaedic procedures1,2.  VTE consists of DVT and pulmonary embolism (PE).  The majority of DVT occur in the lower extremities.  Prompt diagnosis and initiation of therapy is crucial since more than 50% of untreated DVT will result in recurrent VTE, clot embolization to the lungs or post thrombotic syndrome3.  Importantly, excluding a diagnosis of DVT is essential as anticoagulant treatment entails a risk of fatal bleeding, and thus, is only indicated based on objective diagnosis.  In the less likely event of upper extremity DVT, the risk of recurrence, embolization, and post thrombotic syndrome are exceedingly rarer compared to DVT of the lower extremity.

The diagnostic approach to suspected DVT is based on an assessment of the clinical pretest probability.  Unless the probability is low, imaging techniques are required to establish the diagnosis of lower or upper extremity DVT4.  There are several imaging modalities available to confirm or exclude a diagnosis of DVT.  In the past, contrast venography was considered to be the gold standard diagnostic modality, but the invasive nature and high cost of this test has largely limited its routine use in the diagnostic workup of suspected DVT4.  Additional limitations include the discomfort for patients, contraindication in patients with severe chronic kidney disease or contrast medium allergy, and failure to cannulate the dorsal foot veins in 5% of patients5–7.  Further, inadequate visualization of a venous segment may be encountered in up to 20% of venograms8–11.  Computed tomography (CT) and magnetic resonance (MR) venography are alternatives, although they typically also involve injection of contrast media and therefore share similar disadvantages with conventional venography.  MR non-contrast thrombus imaging (MR-NCTI) is one imaging modality with the potential to replace venography as second-line diagnostic test12,13.  This technique involves visualizing the acute thrombus, which appears as a high signal due to red cell methemoglobin in the clot, against a suppressed background14,15.  Despite its advantages of being non-invasive and not requiring intravenous contrast agents, this MRI technique has not been sufficiently evaluated and is not routinely available in most centers.

The most common non-invasive imaging modality for suspected DVT is venous compression ultrasonography (CUS)16–18.  For proximal DVT, this diagnostic test has been reported to have a sensitivity and specificity of 97% and 98%, respectively19.  This was echoed by a recent meta-analysis that reported a sensitivity and specificity of 90.1% and 98.5%, 94.0% and 97.3%, and 97.9% and 99.8% for proximal leg, whole-leg, and serial CUS, respectively20.  The sensitivity and specificity of CUS is substantially lower for diagnosing isolated distal DVT (IDDVT), which is defined as a thrombus involving any vein distal to the popliteal vein at the knee.

The choice between proximal leg and whole-leg CUS should be guided by an assessment of clinical pretest probability.  Proximal leg CUS involves scanning the common femoral and the popliteal vein regions, or of all segments of the deep venous system between the groin and the calf trifurcation where the calf veins join the popliteal vein; whole-leg CUS includes additional scanning of the deep calf veins.  Failure to fully compress the lumen of the veins with the ultrasound probe is confirmatory of DVT21.  A negative proximal CUS excludes a clinically important proximal DVT but does not exclude an IDDVT.  As up to 10% of patients with IDDVT will progress to proximal DVT22–24, patients with a high pretest probability and a normal proximal leg CUS should undergo a serial CUS one week later to exclude proximal extension of a distal DVT16–18,25, and anticoagulation can be safely withheld between serial ultrasounds in standard-risk patients.  Although it is tempting to scan the distal veins to reduce the need for serial CUS, it is important to acknowledge the limitations of whole-leg CUS.  First, it is more technically challenging compared to proximal leg CUS, and there is greater risk of false positives26,27.  Second, whole-leg CUS is also more complex and takes additional time, whereas proximal leg CUS takes only a few minutes28.  Lastly, most institutions do not routinely perform whole-leg CUS.  Furthermore, a true positive IDDVT found on whole-leg CUS has unclear significance, since over 90% of patients with IDDVT will not progress to proximal DVT or PE22–24.  In higher-risk patients (e.g., thrombus in close proximity to the deep venous system, extensive thrombus, history of VTE, malignancy, etc.), anticoagulation is recommended over observation for IDDVT27.  Therefore, whole-leg CUS may be preferred over serial proximal CUS.  D-dimer measurement is of limited value as elevated levels are non-specific for DVT and can be expected in all patients after orthopaedic surgery.  A negative result would exclude the diagnosis of a DVT including IDDVT, but a “false negative” result due to heparin thromboprophylaxis needs to be considered particularly with the use of less sensitive assays23.

Upper extremity DVT (UEDVT) is a rare presentation of VTE, accounting for only 5–10% of venous thromboses29,30.  Similar to lower extremity DVT, the imaging test of choice is CUS16–18.  Notwithstanding, diagnosing UEDVT with CUS is more complex in the upper extremities due to the anatomy, particularly in the axillary and clavicular region where veins are difficult to compress.  Consequently, CUS is often used together with doppler ultrasonography to evaluate a suspected UEDVT.  Contrast venography is limited by the same shortcomings as stated above.  Moreover, due to the infrequent use of venography, radiologists may have a limited experience diagnosing UEDVT using this imaging modality31.  CT venography and MR-NCTI are alternatives, although studies assessing its diagnostic accuracy in UEDVT are scarce13,32.

As the signs and symptoms of DVT are non-specific, the diagnosis is only confirmed in less than 20% of patients investigated for suspected cases33.  Multiple imaging tools are available to assist in confirming a diagnosis, although clinicians should always consider the diagnostic accuracy, costs, and potential adverse effects when selecting the optimal modality.  As it is unnecessary to perform imaging in all patients in whom DVT is suspected, established diagnostic algorithms including an assessment of clinical pretest probability and D-dimer testing should be followed16–18.  Further investigation for the optimal clinical prediction rules, D-dimer strategies, and imaging-first approaches in the setting of orthopaedic procedures is necessary.

References:

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2.         Runner RP, Gottschalk MB, Staley CA, Pour AE, Roberson JR. Utilization Patterns, Efficacy, and Complications of Venous Thromboembolism Prophylaxis Strategies in Primary Hip and Knee Arthroplasty as Reported by American Board of Orthopedic Surgery Part II Candidates. J Arthroplasty. 2019;34(4):729-734. doi:10.1016/j.arth.2018.12.015

3.         Kearon C. Natural history of venous thromboembolism. Circulation. 2003;107(23 Suppl 1):I22-30. doi:10.1161/01.CIR.0000078464.82671.78

4.         Khan F, Tritschler T, Kahn SR, Rodger MA. Venous thromboembolism. The Lancet. 2021;398(10294):64-77. doi:10.1016/S0140-6736(20)32658-1

5.         Heijboer H, Büller HR, Lensing AW, Turpie AG, Colly LP, ten Cate JW. A comparison of real-time compression ultrasonography with impedance plethysmography for the diagnosis of deep-vein thrombosis in symptomatic outpatients. N Engl J Med. 1993;329(19):1365-1369. doi:10.1056/NEJM199311043291901

6.         Lensing AW, Prandoni P, Büller HR, Casara D, Cogo A, ten Cate JW. Lower extremity venography with iohexol: results and complications. Radiology. 1990;177(2):503-505. doi:10.1148/radiology.177.2.2217792

7.         AbuRahma AF, Powell M, Robinson PA. Prospective study of safety of lower extremity phlebography with nonionic contrast medium. Am J Surg. 1996;171(2):255-260. doi:10.1016/S0002-9610(97)89562-1

8.         Hull RD, Hirsh J, Carter CJ, et al. Diagnostic efficacy of impedance plethysmography for clinically suspected deep-vein thrombosis. A randomized trial. Ann Intern Med. 1985;102(1):21-28. doi:10.7326/0003-4819-102-1-21

9.         Lensing AW, Büller HR, Prandoni P, et al. Contrast venography, the gold standard for the diagnosis of deep-vein thrombosis: improvement in observer agreement. Thromb Haemost. 1992;67(1):8-12.

10.       Huisman MV, Büller HR, ten Cate JW, Heijermans HS, van der Laan J, van Maanen DJ. Management of clinically suspected acute venous thrombosis in outpatients with serial impedance plethysmography in a community hospital setting. Arch Intern Med. 1989;149(3):511-513.

11.       Huisman MV, Büller HR, ten Cate JW, Vreeken J. Serial impedance plethysmography for suspected deep venous thrombosis in outpatients. The Amsterdam General Practitioner Study. N Engl J Med. 1986;314(13):823-828. doi:10.1056/NEJM198603273141305

12.       van Dam LF, Dronkers CEA, Gautam G, et al. Magnetic resonance imaging for diagnosis of recurrent ipsilateral deep vein thrombosis. Blood. 2020;135(16):1377-1385. doi:10.1182/blood.2019004114

13.       van Dam LF, Dronkers CEA, Gautam G, et al. Detection of upper extremity deep vein thrombosis by magnetic resonance non-contrast thrombus imaging. J Thromb Haemost. 2021;19(8):1973-1980. doi:10.1111/jth.15394

14.       Moody AR. Magnetic resonance direct thrombus imaging. J Thromb Haemost. 2003;1(7):1403-1409. doi:10.1046/j.1538-7836.2003.00333.x

15.       Saha P, Andia ME, Modarai B, et al. Magnetic resonance T1 relaxation time of venous thrombus is determined by iron processing and predicts susceptibility to lysis. Circulation. 2013;128(7):729-736. doi:10.1161/CIRCULATIONAHA.113.001371

16.       Bates SM, Jaeschke R, Stevens SM, et al. Diagnosis of DVT: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e351S-e418S. doi:10.1378/chest.11-2299

17.       Lim W, Le Gal G, Bates SM, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: diagnosis of venous thromboembolism. Blood Adv. 2018;2(22):3226-3256. doi:10.1182/bloodadvances.2018024828

18.       Mazzolai L, Aboyans V, Ageno W, et al. Diagnosis and management of acute deep vein thrombosis: a joint consensus document from the European Society of Cardiology working groups of aorta and peripheral vascular diseases and pulmonary circulation and right ventricular function. Eur Heart J. 2018;39(47):4208-4218. doi:10.1093/eurheartj/ehx003

19.       Segal JB, Eng J, Tamariz LJ, Bass EB. Review of the Evidence on Diagnosis of Deep Venous Thrombosis and Pulmonary Embolism. The Annals of Family Medicine. 2007;5(1):63-73. doi:10.1370/afm.648

20.       Bhatt M, Braun C, Patel P, et al. Diagnosis of deep vein thrombosis of the lower extremity: a systematic review and meta-analysis of test accuracy. Blood Adv. 2020;4(7):1250-1264. doi:10.1182/bloodadvances.2019000960

21.       Wells PS, Ihaddadene R, Reilly A, Forgie MA. Diagnosis of Venous Thromboembolism: 20 Years of Progress. Ann Intern Med. 2018;168(2):131-140. doi:10.7326/M17-0291

22.       Righini M, Galanaud J-P, Guenneguez H, et al. Anticoagulant therapy for symptomatic calf deep vein thrombosis (CACTUS): a randomised, double-blind, placebo-controlled trial. Lancet Haematol. 2016;3(12):e556-e562. doi:10.1016/S2352-3026(16)30131-4

23.       Robert-Ebadi H, Righini M. Should we diagnose and treat distal deep vein thrombosis? Hematology Am Soc Hematol Educ Program. 2017;2017(1):231-236. doi:10.1182/asheducation-2017.1.231

24.       Righini M, Paris S, Le Gal G, Laroche J-P, Perrier A, Bounameaux H. Clinical relevance of distal deep vein thrombosis. Review of literature data. Thromb Haemost. 2006;95(1):56-64.

25.       Kraaijpoel N, Carrier M, Le Gal G, et al. Diagnostic accuracy of three ultrasonography strategies for deep vein thrombosis of the lower extremity: A systematic review and meta-analysis. PLoS One. 2020;15(2):e0228788. doi:10.1371/journal.pone.0228788

26.       Kearon C, Ginsberg JS, Hirsh J. The role of venous ultrasonography in the diagnosis of suspected deep venous thrombosis and pulmonary embolism. Ann Intern Med. 1998;129(12):1044-1049. doi:10.7326/0003-4819-129-12-199812150-00009

27.       Kearon C. Diagnosis of suspected venous thromboembolism. Hematology Am Soc Hematol Educ Program. 2016;2016(1):397-403. doi:10.1182/asheducation-2016.1.397

28.       Needleman L, Cronan JJ, Lilly MP, et al. Ultrasound for Lower Extremity Deep Venous Thrombosis: Multidisciplinary Recommendations From the Society of Radiologists in Ultrasound Consensus Conference. Circulation. 2018;137(14):1505-1515. doi:10.1161/CIRCULATIONAHA.117.030687

29.       Spencer FA, Emery C, Lessard D, Goldberg RJ, Worcester Venous Thromboembolism Study. Upper extremity deep vein thrombosis: a community-based perspective. Am J Med. 2007;120(8):678-684. doi:10.1016/j.amjmed.2006.06.046

30.       Muñoz FJ, Mismetti P, Poggio R, et al. Clinical outcome of patients with upper-extremity deep vein thrombosis: results from the RIETE Registry. Chest. 2008;133(1):143-148. doi:10.1378/chest.07-1432

31.       Dronkers CEA, Klok FA, Huisman MV. Current and future perspectives in imaging of venous thromboembolism. J Thromb Haemost. 2016;14(9):1696-1710. doi:10.1111/jth.13403

32.       Bosch FTM, Nisio MD, Büller HR, van Es N. Diagnostic and Therapeutic Management of Upper Extremity Deep Vein Thrombosis. J Clin Med. 2020;9(7):E2069. doi:10.3390/jcm9072069

33.       Dronkers CEA, Ende-Verhaar YM, Kyrle PA, et al. Disease prevalence dependent failure rate in diagnostic management studies on suspected deep vein thrombosis: communication from the SSC of the ISTH. J Thromb Haemost. 2017;15(11):2270-2273. doi:10.1111/jth.13805

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