Villalta Score for post-thrombotic syndrome (PTS)

Clinical background

The post-thrombotic syndrome (PTS) occurs in 20–50% of patients who have had a deep vein thrombosis (DVT) of the leg and is its commonest long-term complication [7]. Since there is no objective gold standard test for making the diagnosis, PTS diagnosis rests on typical symptoms and clinical signs in a limb previously affected by DVT [1]. Without a standardised instrument, definitions vary between studies, making it impossible to compare outcomes or pool data in meta-analyses. The Villalta score was developed to meet this need: a reproducible, clinically applicable instrument that both diagnoses PTS and grades its severity [1,2]. Since its introduction, the score has become the most widely used outcome measure for PTS in clinical trials and is recommended as the standard diagnostic instrument by the International Society on Thrombosis and Haemostasis (ISTH) [1].

Calculating the Villalta score

The score is the sum of five patient-reported symptoms and six clinically assessed signs, each graded from 0 (none) to 3 (severe). Eleven scored variables of at most 3 points each give a maximum total of 33. The presence of a venous leg ulcer is recorded separately as yes or no and adds no points, but classifies the limb as severe PTS regardless of the total:

$$\text{Villalta} = \sum_{i=1}^{5} S_i + \sum_{j=1}^{6} T_j$$

where $S_i$ are patient-reported symptoms (pain, cramps, heaviness, paraesthesia, pruritus), $T_j$ are clinically assessed signs (pretibial oedema, skin induration, hyperpigmentation, redness/erythema, venous ectasia, pain on calf compression), each graded 0–3. A venous leg ulcer is not part of the sum, but automatically classifies the limb as severe PTS regardless of the numerical score.

The scale was developed by Prandoni and co-workers in 1992 and introduced as an abstract by Villalta in 1994 [3]. It was constructed as a disease-specific assessment instrument for diagnosing and classifying PTS after DVT of the leg. In a systematic review of all available scoring systems for PTS, Villalta was the only instrument to meet all six appraisal criteria: interobserver reliability, association with ambulatory venous pressure, ability to grade severity, ability to capture change over time and association with patient-reported symptom severity [2]. A systematic review recommended Villalta, combined with a disease-specific quality-of-life questionnaire, as the gold standard for PTS diagnosis [2].

The ISTH standardisation committee adopted the Villalta score in 2009 as the recommended instrument for measuring PTS in clinical studies [1].

Interpretation in practice

A score of 5 is the established threshold for diagnosing PTS [3]. A patient below this threshold at a follow-up visit can be regarded as free of PTS, but should be reassessed if symptoms persist or new ones appear, since PTS can develop up to two years after the DVT [7].

The timing of assessment is crucial. The score should not be calculated earlier than 3–6 months after the acute DVT, since persisting acute symptoms can produce raised scores that do not reflect chronic venous dysfunction [1,7]. The VAS European Independent Foundation recommends assessment at 3–6 months and thereafter periodically according to an individual plan depending on the presence and severity of PTS [7].

Validation and performance

An external validation in Brazilian patients (50 participants, mean age 54 years, on average 12 years after DVT) found an intraobserver agreement with a simple kappa of 0.73 and an interobserver kappa of 0.67, corresponding to substantial and good agreement respectively [3]. The correlation between the Villalta score and the clinical component of the CEAP classification (CEAP C) was high, above 0.9 [3]. On duplex ultrasound, a higher Villalta score correlated with the presence of venous reflux and recanalised veins, and with an initially femoropopliteal DVT territory compared with distal veins [3].

A British validation study (40 legs in 34 patients with PTS) showed moderate to good correlation between the Villalta score and the Venous Clinical Severity Score (VCSS; Spearman r = 0.609) and CEAP C (r = 0.556) [4]. Against a haemodynamic reference (venous filling index by air plethysmography) the correlation was r = 0.499 [4]. Within the Villalta score itself, no correlation could be detected between the patient-reported symptoms and the clinical signs, which may reflect that symptoms and signs capture partly different aspects of PTS [4]. At the same time, the correlation improved with VCSS (r = 0.775) and CEAP C (r = 0.779) when the patient-reported part was excluded, suggesting that the clinical signs are more strongly associated with other venous assessment instruments [4].

Diagnostic accuracy against a clinical reference standard has been challenged. A Norwegian study of 88 patients with proximal DVT (2006–2009) found a sensitivity of 75% (95% CI 60–87%) and a specificity of 66% (95% CI 50–80%) when four predefined clinical criteria were used as the reference [5]. Fifteen patients were diagnosed with PTS on the Villalta score alone; these more often had pain or comorbidity that could explain the leg symptoms [5]. A US study of 288 patients found a similar sensitivity (71.4%) but a higher specificity (95.9%) against a reference based on duplex ultrasound and clinical assessment [6].

Limitations

The most frequent criticism of the Villalta score is its dependence on subjective assessment, both of patient-reported symptoms and of clinically assessed signs [2,4]. The patient-reported symptoms and the clinical signs do not correlate with each other within the score, which means that two patients with the same total score may have very different clinical presentations [4].

An important source of error is pre-existing chronic venous disease (CVD). In patients with primary CVD and a history of DVT, the positive bias was 42.3%, that is, almost half of them were incorrectly classified as having PTS [6]. The score may therefore overestimate the prevalence of PTS in populations with a high frequency of primary venous insufficiency. The VAS position paper therefore recommends that pre-existing venous insufficiency be investigated and taken into account when classifying PTS [7].

The score gives equal weight to all five symptoms and all six signs, regardless of how strongly each individual element correlates with actual venous dysfunction. There are no weights for the site or severity of specific signs, and a venous leg ulcer adds no points at all but automatically recategorises the limb as severe PTS, which can create a discrepancy between the total score and the clinical severity.

The score has been validated in adults with DVT of the leg and should not be used in children, or for PTS after DVT of the arm, without separate validation. The sensitivity in the Norwegian study (75%) means that a quarter of patients with clinical PTS are not identified by the score [5], which limits its usefulness as a stand-alone diagnostic instrument.

References

1. Kahn SR et al. Definition of post-thrombotic syndrome of the leg for use in clinical investigations: a recommendation for standardization. J Thromb Haemost 2009;7(5):879–83. PMID: 19175497
2. Soosainathan A et al. Scoring systems for the post-thrombotic syndrome. J Vasc Surg 2013;57(1):254–61. PMID: 23182156
3. de Ávila RB et al. External validation of Villalta score in high-middle income country patients with deep vein thrombosis. Medicine 2022;101(24):e29367. PMID: 35713439
4. Lattimer CR et al. Validation of the Villalta scale in assessing post-thrombotic syndrome using clinical, duplex, and hemodynamic comparators. J Vasc Surg Venous Lymphat Disord 2014;2(1):8–14. PMID: 26992962
5. Engeseth M et al. Limitations of the Villalta scale in diagnosing post-thrombotic syndrome. Thromb Res 2019;184:62–66. PMID: 31707153
6. Ning J et al. Biases of Villalta scale in classifying post-thrombotic syndrome in patients with pre-existing chronic venous disease. J Vasc Surg Venous Lymphat Disord 2020;8(6):1025–1030. PMID: 32205129
7. Cosmi B et al. The Post-thrombotic Syndrome-Prevention and Treatment: VAS-European Independent Foundation in Angiology/Vascular Medicine Position Paper. Front Cardiovasc Med 2022;9:762443. PMID: 35282358