Abstract
Summary. Isolated distal deep vein thromboses (IDDVT) represent up to 50 % of legs deep vein thromboses (DVT). However, since their natural history is to date unknown, the need to diagnose and treat them is a matter of debate. The diagnostic strategy based on the assessment of pre-test probability and D-dimer demonstrated a scarse efficiency for IDDVT. The choice between a proximal and a complete ultrasonographic approach should be guided by the clinical context, the local expertise and the patient characteristics. Randomized and observational studies have analyzed the need of therapy and compared different regimens of anticoagulation, with conflicting results. Systematic reviews and meta-analyses tend to support the usefulness of an anticoagulant treatment, even if the optimal dose and duration are not still defined. A careful stratification of the patient’s profile, taking into account risk factors for proximal extension, recurrence and bleeding should address the therapeutic approach, which must always be discussed with an adequately informed patient. Further studies aimed to clarify the natural history of IDDVT, and to assess safety and efficacy of lower intensity and shorter duration protocols are urgently needed.
References
1 VTE impact Assessment Group in Europe (VITAE) Venous thromboembolism (VTE) in Europe. The number of VTE events and associated morbidity and mortality. Thromb Haemost. 2007;98:756–64.
2 Risk of deep vein thrombosis following a single native whole-leg compression ultrasound: a systematic review and meta-analysis. JAMA. 2010;303:438–45.
3 Clinical relevance of distal deep vein thrombosis. Review of literature data. Thromb Haemost. 2006;95:56–64.
4 The anticoagulation of calf thrombosis (ACT) project. Chest. 2014;146:1468–77.
5 Short-term natural history of isolated gastrocnemius and soleal vein thrombosis. J Vasc Surg. 2003;37:523–7.
6 Evolution of untreated calf deep-vein thrombosis in high risk symptomatic outpatients: the blind, prospective CALTHRO study. Thromb Haemost. 2010;104:1063–70.
7 . Clinical relevance of distal deep vein thrombosis. Curr Opin Pulm. Med. 2008;14:408–13.
8 Compression ultrasonography for diagnostic management of patients with clinically suspected deep vein thrombosis: prospective cohort study. BMJ. 1998;316:17–20.
9 . Systematic review of the complications following isolated calf deep vein thrombosis. BJS. 2016;103:789–96.
10 . Silent pulmonary embolism in patients with distal deep venous thrombosis: systematic review. Thromb Res. 2014;134:1182–5.
11 . Comparison of the clinical history of symptomatic isolated distal deep-vein thrombosis vs. proximal deep vein thrombosis in 11086 patients. J Thromb Haemost. 2009;7:2018–34.
12 Compartive study on risk factors and early outcome of symptomatic distal versus proximal deep vein thrombosis: results from the OPTIMEV study. Thromb Haemost. 2009;102:493–500.
13 Isolated distal deep vein thrombosis: perspectives from the GARFIELD-VTE Registry. Thromb Haemost. 2019;19(10):1675–85.
14 Does the clinical presentation and extent of venous thrombosis predict likelihood and type of recurrence? A patient-level meta-analysis. J Thromb Haemost. 2010;8:2436–42.
15 Incidence and predictors of venous thromboembolism recurrence after a first isolated distal deep vein thrombosis. J Thromb Haemost. 2014;12:436–43.
16 Two years outcome of isolated distal deep vein thrombosis. Thromb Res. 2014;134:36–40.
17 Long-term recurrence of venous thromboembolism after short-term treatment of symptomatic isolated distal deep vein thrombosis: a cohort study. Vascular Medicine. 2017;22:518–24.
18 The long-term recurrence risk of patients with unprovoked venous thromboembolism: an observational cohort study. J Thromb Haemost. 2016;14:2402–9.
19 Probability of developing proximal deep-vein thrombosis and/or pulmonary embolism after distal deep-vein thrombosis. Thromb Haemost. 2016;115:608–14.
20 Long-term outcomes of cancer-related isolated distal deep vein thrombosis: the OPTIMEV study. J Thromb Haemost. 2017;15:907–16.
21 Survival and recurrent venous thromboembolism in patients with first proximal or isolated distal deep vein thrombosis and no pulmonary embolism. J Thromb Haemost. 2017;15:1436–42.
22 Predictors of the post-thrombotic syndrome with non-invasive venous examinations in patients 6 weeks after a first episode of deep vein thrombosis. J Thromb Heamost. 2010;8:2685–92.
23 Determinants and time course of the post-thrombotic syndrome after acute deep vein thrombosis. Ann Intern Med. 2008;149:698–707.
24 . Is it worth diagnosing and treating distal deep vein thrombosis? No. J Thromb Haemost. 2007;5:55–9.
25 , Distal DVT: worth diagnosing? Yes. J Thromb Haemost. 2007;5:51–4.
26 . Should we be looking for and treating isolated calf vein thrombosis? Emerg Med J. 2016;33:431–7.
27 . Should we diagnose and treat distal deep vein thrombosis? Hematology Am Soc Hematol Educ Program. 2017;2017:231–6.
28 Diagnosis of DVT, Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based clinical Practice Guidelines. Chest. 2012;141:e351S–e418S.
29 American Society of Hematology 2018 guidelines for management of venous thromboembolism: diagnosis of venous thromboembolism. Blood Adv. 2018;2:3226–56.
30 The Wells rule and the D-dimer for the diagnosis of isolated distal depep vein thrombosis. J Thromb Haemost. 2012;10:2264–9.
31 Measurement of the clinical and cost- effectiveness of non-invasive diagnostic testing strategies for deep vein thrombosis. Healt Technology Assessment. 2006;10:1–168.
32 . Meta-analysis: the value of clinical assessment in the diagnosis of deep venous thrombosis. Ann Intern Med. 2005;143:129–39.
33 Performance of Wells score for deep vein thrombosis in the inpatient setting. JAMA Inter Med. 2015;175:1112–7.
34 Comparison of the diagnostic performance of the original and modified Wells score in inpatients and outpatients with suspected deep vein thrombosis. Thromb Res. 2011;127:535–9.
35 Proximal and isolated distal deep vein thrombosis and Wells score accuracy in hospitalized patients. Intern Emerg Med. 2019;14(6):941–7.
36 Exclusion of deep vein thrombosis using the Wells rule in clinically important subgroups: individual patient data meta-analysis. BMJ. 2014;348:g1340.
37 Using an age-dependent D-dimer cut-off value increases the number of older patients in whom deep vein thrombosis can be safely excluded. Hematologica. 2012;97:1507–13.
38 Limitations of D-dimer testing in unselected inpatients with suspected venous thromboembolism. Am J Med. 2003;114:276–82.
39 Does this patient have deep vein thrombosis? JAMA. 2006;295:199–207.
40 Normal D-dimer concentration is a common finding in symptomatic outpatients with distal deep vein thrombosis. Blood Coagul Fibrinolysis. 2005;16:517–23.
41 . Complete compression ultrasound for the diagnosis of venous thromboembolism. Curr Opin Pulm Med. 2004;10:350–5.
42 . Diagnostic management of acute deep vein thrombosis and pulmonary embolism. J Thromb Haemost. 2013;11:412–22.
43 Diagnostic management of clinically suspected acute deep vein thrombosis. Br J Haematol. 2009;146:347–360.
44 Systematic review and meta-analysis of the diagnostic accuracy of ultrasonography for deep vein thrombosis. BMC Med Imaging. 2005;5:6.
45 Withholding anticoagulation following a single native whole-leg ultrasound in patients at high pretest probability for deep vein thrombosis. Clin Appl Thromb Hemost. 2013;19:79–85.
46 Serial 2-point ultrasonography plus D-dimer vs whole-leg color-coded doppler ultrasonography for diagnosing suspected symptomatic deep vein thrombosis: a randomized controlled trial. JAMA. 2008;300:1653–9.
47 Safety and sensitivity of two ultrasound strategies in patients with clinically suspected deep venous thrombosis: a prospective management study. J Thromb Haemost. 2009;7:2035–41.
48 A single complete ultrasound investigation of the venous network for the diagnostic management of patients with a clinically suspected first episode of deep venous thrombosis of the lower limbs. Thromb Haemost. 2003;89:221–7.
49 Single whole-leg compression ultrasound for exclusion of deep vein thrombosis in symptomatic ambulatory patients: a prospective observational cohort study. BJH. 2014;164:422–30.
50 Interobserver agreement of complete compression ultrasound for clinically suspected deep vein thrombosis. Clin Appl Thromb Hemost. 2002;8:45–9.
51 Randomized prospective study comparing routine versus selective use of sonography of the complete calf in patients with suspected deep venous thrombosis. AJR Am J Roentgenol. 2003;180:241–5.
52 Analysis of an algorithm incorporating limited and whole-leg assessment of deep venous system in symptomatic outpatients with suspected deep-vein thrombosis (PALLADIO): a prospective, multicentre, cohort study. Lancet Hematol. 2015;2:e474–80.
53 Outcomes for inpatients with normal findings on whole-leg ultrasonography: a prospective study. Am J Med. 2010;123:158–65.
54 Ultrasound for lower extremity deep venous thrombosis. Circulation. 2018;137:1505–15.
55 Ultrasound elastography is useful to distinguish acute and chronic vein thrombosis. J Thromb Haemost. 2018;16:2482–91.
56 Asymptomatic lower extremity deep vein thrombosis-clinical characteristics, management strategies and long-term outcomes. Circ J. 2017;81:1936–44.
57 Practice variation in the management of distal deep vein thrombosis in primary vs. secondary cares: a clinical practice survey. Thromb Res. 2015;136:526–30.
58 Therapeutic anticoagulation for isolated calf deep vein thrombosis. JAMA Surgery. 2016;151:e161770.
59 Need for long-term anticoagulant treatment in symptomatic calf-vein thrombosis. Lancet. 1985;2:515–18.
60 Comparison of 3 and 6 months of oral anticoagulant therapy after a first episode of proximal deep vein thrombosis or pulmonary empbolism and comparison of 6 and 12 weeks of therapy after isolated calf deep vein thrombosis. Circulation. 2001;103:2453–60.
61 Optimal duration of treatment in surgical patients with calf venous thrombosis involving one or more veins. Angiology. 2006;57:418–23.
62 Therapy of isolated calf muscle vein thrombosis: a randomized, controlled study. J Vasc Surg. 2010;52:1246–50.
63 Anticoagulant therapy for symptomatic calf deep vein thrombosis (CACTUS): a randomized, double-blind, placebo-controlled trial. Lancet Haematol. 2016;3:e556–e562.
64 . Anticoagulant therapy for symptomatic calf deep vein thrombosis. The Lancet Hemoatology. 2017;4:156.
65 Ultrasound characteristics of calf deep vein thrombosis and residual vein obstruction after low molecular weight heparin treatment. Eur J Vasc Endovasc Surg. 2016;52:658–64.
66 Management of isolated soleal and gastrocnemius vein thrombosis. J Vasc Surg. 2010;52:1251–4.
67 Early thrombus remodelling of isolated calf deep vein thrombosis. Eur J Vasc Endovasc Surg. 2002;23:344–8.
68 Is anticoagulation indicated for asymptomatic post- operative calf vein thrombosis? J Vasc Surg. 1992;16:141–9.
69 . Short-term and mid-term outcome of isolated symptomatic muscular calf vein thrombosis. J Vasc Surg. 2007;46:513–9.
70 Isolated gastrocnemius and soleal vein thrombosis. Should these patients receive therapeutic anticoagulation? Ann Surg. 2009;251:735–42.
71 Isolated distal deep vein thrombosis: efficacy and safety of a protocol of treatment. Treatment of isolated calf thrombosis (TICT) study. Int Angiol. 2009;28:68–72.
72 . How I treat isolated distal deep vein thrombosis (IDDVT). Blood. 2014;123:1802–9.
73 The controversy of managing calf vein thrombosis. J Vasc Surg. 2012;55:550–61.
74 A meta-analysis of anticoagulation for calf deep venous thrombosis. J Vasc Surg. 2012;56:228–37.
75 Efficacy and safety of therapeutic anticoagulation for the treatment of isolated calf muscle vein thrombosis – a systematic review and meta-analysis. Vasa. 2016;45(6):478–85.
76 Anticoagulation in patients with isolated distal deep vein thrombosis: a meta-analysis, J Thromb Haemost. 2017;15:1142–54.
77 A systematic review and meta-analysis comparing anticoagulation versus no anticoagulation and shorter versus longer duration of anticoagulation for treatment of isolated distal deep vein thrombosis. Semin Thromb Hemost. 2017;43:836–48.
78 Antithrombotic therapy for VTE disease. Chest Guideline and expert panel report. Chest. 2016;149:315–52.
79 Prevention and treatment of venous thromboembolism-International Consensus Statement. Intern Angiol. 2013;32:111–260.