RVO – Real value obscure
Henry G. Watson, Department of Haematology, Aberdeen Royal Infirmary, Foresterhill Health Campus, Aberdeen AB25 2ZN, UK.
Tel.: +44 1224 553394; fax: +44 1224 550714.
See also Carrier M, Rodger MA, Wells PS, Righini M, Le Gal G. Residual vein obstruction to predict the risk of recurrent venous thromboembolism in patients with deep vein thrombosis: a systematic review and meta-analysis. This issue, pp 1119–25; Le Gal G, Carrier M, Kovacs MJ, Betancourt MT, Kahn SR, Wells PS, Anderson DA, Chagnon I, Solymoss S, Crowther M, Righini M, Delluc A, White RH, Vickars L, Rodger M. Residual vein obstruction as a predictor for recurrent thromboembolic events after a first unprovoked episode: data from the REVERSE cohort study. This issue, pp 1126–32.
We would all like to be able to identify those patients referred to us with a history of deep vein thrombosis (DVT) who are most likely to benefit from long-term anticoagulant therapy. Although standard practice is to offer an initial finite period of anticoagulation of between 3 and 6 months, recent guidance has encouraged clinicians to consider the option of long-term anticoagulation after a first episode of thrombosis in cases where the risk of recurrence is considered to be sufficiently high and the risk of bleeding related to anticoagulant therapy is considered to be acceptably low [1–3]. The majority of patients who sustain a DVT do so in the context of a temporary risk factor such as surgery, medical illness, or the use of the combined oral contraceptive pill. The risk of recurrence in these patients, once the risk factor has ceased to be active and anticoagulant therapy has been discontinued, is low , and it is unusual to consider long-term anticoagulation for this group of patients with a provoked first episode of DVT. However, the risk of recurrence following discontinuation of coumarin in patients who have sustained an initial unprovoked episode of DVT is approximately 10% after 1 year, 30% at 3 years, and 50% at 10 years [5,6], and it is within this group that we would like to be able to identify those most likely to benefit from long-term anticoagulation. Research has identified several clinical features that define those at highest risk of recurrence, for example older subjects, males and those with proximal as opposed to distal thrombosis and with severe post-thrombotic syndrome. In addition to these clinical features, several laboratory assays, such as D-dimer  and endogenous thrombin potential , may help to identify those at low risk of recurrence in whom anticoagulation may be safely withheld. It has been hypothesized that the presence of residual thrombus in a deep vein (residual vein occlusion [RVO]) following an episode of DVT might predict recurrence; however, studies have applied various forms of assessment and definitions of RVO, with inconclusive results. In the current edition of the Journal, the value of RVO in predicting recurrence of DVT in patients with a first episode of unprovoked thrombosis following discontinuation of anticoagulation is described , and in addition a systematic review and meta-analysis of studies investigating the value of assessment of RVO in predicting recurrence is presented .
Why might RVO predict recurrence?
It is worthwhile to consider the mechanisms by which RVO might influence DVT recurrence. Presumably, persistent occlusion of a deep vein has an adverse effect on flow in the vessels distal to it. From our understanding of Virchow’s triad, the resulting stasis would increase the risk of recurrent thrombosis. Second, patients with persistent venous occlusion after proximal DVT have a higher risk of developing post-thrombotic syndrome than patients without , and post-thrombotic syndrome has been shown to be an independent risk factor for recurrence of thrombosis [12,13]. RVO is unlikely to represent ongoing thrombus generation, and is perhaps more likely to reflect defective fibrinolysis or possibly some other form of endothelial dysfunction. Defective fibrinolysis has not been demonstrated to influence the risk of initial or recurrent venous thromboembolism (VTE) [14,15] but, nevertheless, defects in fibrinolysis may partially explain the observation of RVO, which does not itself appear to be a strong risk factor for recurrence, based on the available evidence [9,10].
Variations in the methods employed for markers such as D dimer and endogenous thrombin potential have been shown to influence the ability to predict thrombosis recurrence. The assignment of RVO is complicated by the fact that a variety of definitions have been used in the literature to date. All employ compression ultrasound, but different parameters have been applied to define the presence of RVO. Prandoni et al.  defined a vein as being occluded if, under compression, in the transverse plane it measured > 2 mm on a single test or > 3 mm on two consecutive tests, whereas Siragusa et al.  used a definition of thrombus occupying > 40% of the vein diameter, and Young et al.  defined occlusion as any residual thrombus. In addition to the difficulty stemming from the employment of variable definitions of RVO, there has been only moderate interobserver agreement for these types of measurements, with a mean difference between paired measurements of residual vein diameter of 2.2 mm (95th centile, 8.0 mm) . This lack of standardization and poor interobserver agreement represents a significant impediment to the interpretation of these studies and to routine clinical use of this method.
RVO as a predictor of recurrent thrombosis following a first unprovoked episode
The study on the REVERSE cohort, published in this edition of the Journal, investigates what is, to my mind, the key issue that needs to be addressed with regard to the clinical utility of assessment of RVO – its ability to identify groups of patients who would benefit from long-term anticoagulation after an initial period of treatment for a first unprovoked VTE. Furthermore, the study quantified the RVO in order to determine whether the degree of occlusion had any effect on recurrence. The investigators performed a compression ultrasound scan on patients who had completed 5–7 months of anticoagulation with a coumarin after a first episode of VTE. In each patient, they assessed the degree of any RVO observed, classifying it as ‘minimal wall thickening’, ‘partial thrombus resolution’, ‘minimal thrombus resolution’, or ‘stable or worsened thrombus’. Of 452 patients recruited over a 4-year period and followed for mean of 18 months, 45/231 (19.5%) patients with RVO had recurrent thrombosis as compared with 32/220 (14.6%) without RVO (hazard ratio 1.4; 95% confidence interval 0.9–2.1), indicating a small but statistically insignificant effect. Analysis of the quantitative effect of RVO showed a possible small effect of increasing severity of occlusion.
At present, the data on RVO suggest that it does not reliably identify patients with a higher risk of recurrence of thrombosis after discontinuation of an initial period of anticoagulation following a first unprovoked VTE. Although it may have some predictive value for recurrence of all DVTs and pulmonary embolisms, these uses are clinically irrelevant in general. If further studies are to be performed, they should employ an agreed definition of RVO. For now, there is little clinical value in assessing RVO, and it should not be part of standard clinical practice.
Disclosure of Conflict of Interests
The authors state that they have no conflict of interest.