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BET 2: Striking the right balance: anticoagulation and isolated distal deep vein thrombosis
  1. Tom Jones1,
  2. Dan Horner2
  1. 1 University of Manchester, Manchester, UK
  2. 2 Salford Royal NHS Foundation Trust, Salford, UK
  1. Correspondence to Dan Horner, Emerge (Research Office), Emergency Department, Manchester Royal Infirmary, Manchester M13 9WL, UK; katharine.wylie{at}cmft.nhs.uk

Abstract

A short-cut review was carried out to establish whether treatment of isolated distal deep vein thrombosis with therapeutic anticoagulation can reduce adverse clinical outcomes. A meta-analysis from 2011 and 11 subsequent directly relevant papers were found using the reported search strategy. Of these, 7 in total presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. It is concluded that patients diagnosed with isolated distal deep vein thrombosis should be individually risk assessed and treated according to their risk of thrombotic complication, bleeding with anticoagulation and personal preference.

  • emergency department
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Clinical scenario

A 45-year-old woman attends the ED with a painful and swollen right calf. Her Wells score is low risk, but a D-dimer returns over the cut point for your local assay. Whole-leg ultrasound examination later that day confirms thrombosis of the posterior tibial and peroneal veins. She has no other medical history but you cannot identify a clear provoking factor for the thrombus. She is worried and symptomatic.

A colleague reports to you that she does not treat any below-knee deep vein thromboses (DVTs). NICE guidance supports above-leg scanning only, but international guidelines do not support treatment and your colleague also believes that the poor sensitivity of whole-leg ultrasound renders the test unsuitable for clinical decision making.1–3

You are concerned about the idea of leaving an unprovoked isolated distal deep vein thrombosis (IDDVT) untreated in a patient who is symptomatic. However, you also worry about anticoagulation related bleeding. You decide to consult the literature to guide your decision making.

Three-part question

In (symptomatic IDDVT) does (therapeutic anticoagulation) reduce (adverse clinical outcomes)?

Search strategy

MEDLINE 1946 to week 1 in February 2017 using the OVID interface.

[exp Venous Thrombosis/ OR deep vein thrombosis.mp. OR DVT$.mp.] AND [distal.mp. OR below knee.mp. OR calf.mp. OR popliteal.mp. OR exp Popliteal Vein/ OR fibular.mp. OR peroneal.mp. OR posterior tibial.mp.] AND [exp Therapeutics/ OR therapy.mp. OR treatment.mp. OR exp Heparin, Low-Molecular-Weight/ OR exp Heparin/ OR heparin.mp. OR exp Warfarin/ OR warfarin.mp. OR exp Coumarins/ or coumarin.mp. OR exp Anticoagulants/ OR NOACs.mp. OR apixaban.mp. OR exp Rivaroxaban/ OR rivaroxaban.mp. OR edoxaban.mp. OR exp Dabigatran/ OR dabigatran.mp.] LIMIT to human AND English Language.

Search outcome

A previous BET on this topic from 2003 was identified concluding that all patients with calf thrombosis should receive oral anticoagulation.4 The evidence studied in this BET was limited in its generalisability; recent high-level research, including several randomised controlled trials necessitated an update.

Altogether 1399 papers were found using the above search strategy. Titles and abstracts were scrutinised for relevance. An up-to-date meta-analysis from 2011 was identified and the search strategy was evaluated, which seemed robust. Subsequent to this review, 11 papers were found which directly addressed the question. These papers were appraised for inclusion and excluded if they failed to report comparison between two different treatment groups.

This left seven articles total, including one meta-analysis,5 three randomised controlled trials6–8 and three comparator cohort studies (see table 2).9–11

Table 2

BET 2 relevant papers

Comments

Whether patients with IDDVT should receive anticoagulation remains a controversial question, with variable international practice. The current best evidence, summarised above, consists mainly of small prospective cohort studies with an additional limited number of randomised studies, each with methodological limitations.

It is clear that some patients with untreated IDDVT will develop venous thromboembolic event (VTE)-related complications, such as proximal propagation or embolisation. The composite risk of this is roughly 7%–10% within 90 days.12 Certain clinical features suggesting high VTE risk appear to increase the rate of complications. Therapeutic anticoagulation markedly reduces this risk, down to <2% in most studies. However, the benefits of anticoagulation must be balanced against the risks. While the results above present minimal risk associated with anticoagulation, extensive research has been done in this field. A meta-analysis published in 2003 found a major bleeding rate of 2.06% (95% CI 2.04% to 2.08%) during the first 3 months of therapeutic anticoagulation, with a fatal bleeding rate of 0.37% (95% CI 3.6% to 3.8%).13 A lower risk may be associated with the new oral anticoagulants.14

As yet, no large randomised controlled trial has been conducted which compares modern therapeutic anticoagulation in patients with IDDVT directly against conservative management. As such, risks and benefits of treatment must therefore be considered on an individualised basis, prior to shared decision making. The 9th edition of the American College of Chest Physicians guidelines regarding antithrombotic therapy for VTE disease recommend treatment dose anticoagulation in IDDVT patients only with severe symptoms or those with a high risk for thrombus extension.2 These groups are defined as follows: D-dimer is positive (particularly when markedly so without an alternative reason); thrombosis is extensive (eg, >5 cm in length, involves multiple veins, >7 mm in maximum diameter); thrombosis is close to the proximal veins; there is no reversible provoking factor for DVT; active cancer; personal history of VTE; and inpatient status. This evaluation should be accompanied by an assessment of individualised bleeding risk, using validated scoring systems and senior assessment.15 Following these assessments, a discussion with the patient surrounding the risks and benefits of treatment appears to be the most reasonable solution to the clinical question in the absence of definitive evidence. Further robust randomised control trials are warranted to provide guidance on duration of therapy, risk factors for failure of conservative management and bleeding risk in this cohort. Such trials are feasible and necessary.

Level of evidence

Level 2—studies considered were neither 1 nor 3.

Clinical bottom line

Patients diagnosed with isolated distal deep vein thrombosis should be individually risk assessed and treated according to their risk of thrombotic complication, bleeding with anticoagulation and personal preference. Treatment if commenced should consist of therapeutic dose anticoagulation for at least 6 weeks. Further evidence is needed to accurately identify patient factors associated with higher risk of complications and provide randomised trial evidence of event rates with and without treatment

References

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