- Email: [email protected]
Scoring systems for the post-thrombotic syndrome
Scoring systems for the post-thrombotic syndrome Arany Soosainathan, MB BChir, Hayley M. Moore, MRCS, MBBS, MA, Manjit S. Gohel, FRCS, MD, FEBVS, and Alun H. Davies, MA, DM, FRCS, London, United Kingdom Objective: To assess each of the scoring systems used to diagnose and classify post-thrombotic syndrome, a common chronic complication of deep vein thrombosis. The design of the study was a systematic review of the literature pertaining to post-thrombotic syndrome. Methods: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and MetaAnalyses (PRISMA) guidelines by a search of PubMed (1948 to September 2011) using the search terms “postthrombotic syndrome,” “postthrombotic syndrome,” “post-phlebitic syndrome,” and “postphlebitic syndrome.” A manual reference list search was also carried out to identify further studies that would be appropriate for inclusion. The various scoring systems in use were identified and assessed against a list of criteria to determine their validity for use. For outcome measures, each scoring system was assessed for specific criteria, including interobserver reliability, association with ambulatory venous pressures, ability to assess severity of post-thrombotic syndrome, ability to assess change in condition over time, and association with patient-reported symptom severity. Results: The Villalta, Ginsberg, Brandjes, Widmer, CEAP, and Venous Clinical Severity Score systems all were assessed for the stated outcome measures. From their use in the literature, only the Villalta score was able to fulfill all the criteria described. The main criticism of the Villalta score in the literature appears to be its use of subjective measures. To that end, we propose that use of a venous disease-specific quality-of-life questionnaire in combination with the Villalta score may help standardize the subjective criteria. Conclusions: The Villalta score, combined with a venous disease-specific quality-of-life questionnaire, should be considered the “gold standard” for the diagnosis and classification of post-thrombotic syndrome. (J Vasc Surg 2013;57:254-61.)
Deep vein thrombosis (DVT) of the lower limbs is both a common and a serious disease, with an estimated incidence of 1 per 1000 people per year.1 It can have a clear precipitant, such as surgery, malignancy, or inherited coagulation disorders, or occur spontaneously. A number of complications can follow DVT. The incidence and outcomes of acute complications such as pulmonary embolism are well reported, but post-thrombotic syndrome (PTS) is less well understood. This is a chronic condition, occurring in at least one third of patients who have a DVT.2 It may be associated with leg pain and heaviness, edema, hyperpigmentation, lipodermatosclerosis, and venous ulceration, occurring to varying degrees in different patients. The pathophysiology underlying PTS is thought to be sustained venous hypertension, resulting from obstruction to venous flow, vein valvular incompetence, or a combination. As there is a considerable degree of overlap between the acute symptoms resulting from a DVT and those of PTS, there is a minimum time period (ranging from 6 months to 2 years in various studies3-5) before
From the Academic Section of Vascular Surgery, Department of Surgery & Cancer, Imperial College School of Medicine, Charing Cross Hospital. Author conflict of interest: none. Reprint requests: Professor Alun H. Davies, Academic Section of Vascular Surgery, Department of Surgery & Cancer, Imperial College School of Medicine, Charing Cross Hospital, Fulham Palace Road, London, W6 8RF, United Kingdom (e-mail: [email protected]). The editors and reviewers of this article have no relevant financial relationships to disclose per the JVS policy that requires reviewers to decline review of any manuscript for which they may have a conflict of interest. 0741-5214/$36.00 Copyright Ó 2013 by the Society for Vascular Surgery. http://dx.doi.org/10.1016/j.jvs.2012.09.011
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the condition is diagnosed. Patients with PTS have a significantly decreased quality of life6 and the condition can result in a substantial psychological and economic burden.7 However, although there is a large body of research concerning the natural history and treatment options of acute DVT, there is less evidence on the diagnosis and management of PTS. One of the reasons often cited for this is the lack of a clear gold standard definition of PTS. Instead, several scoring systems are used to both diagnose the condition and classify its severity. This review aims to describe the main scoring systems, illustrate how they have been used in studies investigating PTS, and outline whether one scoring system demonstrates advantages over the others. METHODS This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.8 The relevant studies and reviews were found through systematic searches of PubMed (1948 to September 2011). The search terms used were “postthrombotic syndrome,” “postthrombotic syndrome,” “post-phlebitic syndrome,” and “postphlebitic syndrome.” A manual reference list search was also carried out to identify further studies that would be appropriate for inclusion. The titles of the search results were screened with human and English language limits to identify the studies to be included. The abstracts and full text of these were then examined by two of the authors (A.S., H.M.) to identify those relevant to this review’s scope, namely, those that referred to a PTS scoring system. Articles concerning the upper limb and children were excluded. All other articles including prospective and
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Fig 1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) diagram. Summary of search strategy and results of literature review.
retrospective studies, human participants, data related to adult (>18 years) patients, and lower limbs were included. Once the relevant articles were obtained, a list of the main PTS scoring systems in use was made. Each scoring system was then assessed for validity of use according to specific criteria, including interobserver reliability, association with ambulatory venous pressures (AVPs), ability to assess severity of PTS, ability to assess the change in condition over time, and association with patient-reported symptom severity. RESULTS The search strategy, carried out as described in Fig 1, resulted in 37 publications that fulfilled the inclusion criteria. Villalta. The Villalta score is a disease score specific for PTS.9 It can be used to both diagnose and categorize the severity of the condition. It was developed in a crosssectional study of 100 patients who were assessed 6 to 36 months after DVT. Points are given for five symptoms
(pain, cramps, heaviness, paresthesia, pruritus) and six clinical signs (pretibial edema, skin induration, hyperpigmentation, redness, venous ectasia, pain on calf compression). Points are given for each of these 11 descriptors according to severity (Table I), ranging from 0 for not present to 3 for severe. Furthermore, if a venous ulcer was present, the severity of the condition was classified as severe, regardless of the presence or absence of other signs or symptoms. The patient was diagnosed as having PTS if the Villalta score was $5 or if a venous ulcer was present. A score of 5-9 signifies mild disease, 10-14 moderate disease, and $15 severe disease. The Villalta score was used in several studies to diagnose PTS.2,10-15 Five studies used the Villalta score as originally described, with scores >5 confirming the diagnosis of PTS and a score >14 denoting severe PTS,2,10,12-15 and one study used a modified Villalta score, giving a final score out of 9, with 4 being diagnostic and 7 the threshold for severe PTS.11 When a diagnosis of PTS is made using the Villalta score, only one assessment giving a score >5 is
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Table I. Villalta’s PTS score9 Symptoms/clinical signs Symptoms Pain Cramps Heaviness Paresthesia Pruritus Clinical signs Pretibial edema Skin induration Hyperpigmentation Redness Venous ectasia Pain on calf compression Venous ulcer
None
Table II. Uses of the Villalta score in various studies Mild
Moderate
Severe Author (year)
0 0 0 0 0
points points points points points
1 1 1 1 1
point point point point point
2 2 2 2 2
points points points points points
3 3 3 3 3
points points points points points
0 points 0 points 0 points 0 points 0 points 0 points Absent
1 1 1 1 1 1
point point point point point point
2 2 2 2 2 2
points points points points points points
3 points 3 points 3 points 3 points 3 points 3 points Present
PTS, Post-thrombotic syndrome.
required, in contrast to certain other scores, which require multiple assessments, with a set time interval in between. The Villata score has also been used as a continuous measurement for longer-term follow-up3,16 to grade the severity of the condition6,17 and to assess the effectiveness of treatments (Table II).17-19 The score has also been shown to yield reliable consistent results, whether used by physicians9 or by other health professionals trained in using the scale.20 As such, use of the Villalta score can be justified, whether in clinic settings to monitor the progress of patients or in studies assessing the impact of treatment. In addition, Villalta scores in patients with PTS appear to correlate with patient-perceived quality of life as well as with clinical measurements thought to be related to the pathophysiology underlying PTS, thus suggesting the Villalta score is a valid scale for clinical use.6,21,22 Two studies assessed both the generic and the disease-specific healthrelated quality of life after DVT.6,21 They showed that although quality-of-life scores tended to improve from baseline after DVT, patients who developed PTS had significantly worse disease-specific quality-of-life scores.6,21 These lower scores were not present on the generic qualityof-life scores, thus attributing the difference to the condition. The results of the two studies, showing how the Villalta scores correlate with quality-of-life scores, are summarized in Fig 2.6,21 In these two studies, the Villalta score was used to categorize PTS into mild, moderate, and severe (Table I). The Venous Insufficiency Epidemiological and Economic Study/Quality of Life (VEINES-QOL) and the Venous Insufficiency Epidemiological and Economic Study/Symptoms (VEINES-Sym) are patient-reported outcome scores that can be computed from a 25-item questionnaire. The items cover symptoms (heavy legs, aching legs, swelling, night cramps, heat or burning sensation, restless legs, throbbing, itching, tingling sensation, leg pain), limitations in daily activities, change over the past year, and psychological impact. The VEINES-QOL summary score aims to measure the overall impact of venous disease on a patient’s life. The VEINES-Sym score
No. enrolled (completed follow-up)
355 (245) Prandoni et al2 (1996) 300 (244) Van Dongen et al10 (2005) 11 1916 (1668) Tick et al (2008) 359 Kahn et al12 (2005) 116 (110) Roumen-Klappe et al13 (2009) 145 Kahn et al14 (2005) 69 Roumen-Klappe et al15 (2009) 41 Kahn et al6 (2002) 43 (39) Kahn et al17 (2011) 528 Prandoni et al3 (1997) 387 (260) Kahn et al16 (2008) 43 (39) Kahn et al17 (2011) 32 (26) O’Donnell et al18 (2008) 19 120 Prandoni et al (2005)
Application Diagnosis Diagnosis Diagnosis Diagnosis Diagnosis Diagnosis Diagnosis Classify severity Classify severity Long-term follow-up Long-term follow-up Evaluation of treatment Evaluation of treatment Evaluation of treatment
is a subscale that measures the specific impact of symptoms on daily life. In both measures, lower scores indicate lower quality of life. The data from Kahn et al6 have remained unchanged. The data from Kahn et al21 have had the results listed for mild PTS and moderate PTS amalgamated but otherwise unprocessed. In looking at the differences between existing classification systems, Kolbach et al22 examined the association between AVP (measured via invasive methods) and the scores obtained from the various scoring systems. In this study, the Villalta score was one of the systems with a strong association with a high AVP value. However, there was a caveat to this conclusion; there was a considerable degree of overlap in AVPs in the different clinical severities of PTS, indicating that there is not a simplistic linear relationship between venous hypertension and PTS. In the absence of a gold standard with which to define the PTS, the wide spectrum of disease severity, and hence the difficulty in assessing validity of the various scoring systems, these surrogate measures (health-related quality of life and numerical measurements of pathophysiologic markers of the disease) suggest that the Villalta score correlates with the clinical and physiologic markers of the disease. Ginsberg. The Ginsberg score was designed in a crosssectional study looking at PTS developing after hip or knee arthroplasty.5 It diagnosed patients as having PTS if the patient reported leg pain and swelling of a chronic nature (daily, for a period of at least 1 month), typical in character (aggravated by prolonged standing, improved by leg elevation), occurring at least 6 months after the initial DVT. Patients could be diagnosed with PTS only if they had both leg pain and swelling and if there was objective evidence of valvular incompetence. The presence of persistent occlusion was not included. The Ginsberg score was used in a study evaluating the efficacy of graduated
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None Mild/Moderate PTS Severe PTS 70
60
Mean Scores
50
40
30
20
10
0 Mean VEINES-QOL (2002)
Mean VEINES-Sym (2002)
Mean VEINES-QOL (2008)
Mean VEINES-Sym (2008)
Quality of Life Scores
Fig 2. Graph demonstrating quality-of-life scores in patients with different degrees of post-thrombotic syndrome (PTS).6,21
compression stockings in preventing and in treating PTS.23 It also will be used to diagnose PTS in the SOX trial, which was designed to investigate the effectiveness of compression stockings in preventing PTS.24 Kahn et al25 compared the Ginsberg and Villalta scales with respect to the healthrelated quality of life of patients and with venous valvular reflux (as a physiologic indicator of chronic venous disease). In this study, they found that when the Villalta score was used, almost five times as many patients were diagnosed with PTS at 1 year than when the Ginsberg score was used. They also found that patients diagnosed with the condition when the Ginsberg score was used had higher mean numeric Villalta scores and lower quality-oflife scores, suggesting that the Ginsberg scale only identifies those patients with more severe disease. Furthermore, this score does not rate the severity of the condition and may not include patients with predominantly occlusive deep venous disease. Brandjes. The Brandjes score was developed as part of a trial looking at the effect of compression stockings on patients with symptomatic proximal DVT.4 In a manner similar to the Villalta score, points are given for a number of subjective and objective criteria (Table III). These criteria were chosen from combined components of other scoring systems,26,27 and patients were classified as having PTS based on their score over two consecutive visits, 3 months apart. A score of 3 or higher (including one objective criterion) diagnosed mild-moderate PTS, whereas a score of 4 or more from a list of more severe
subjective and objective criteria defined severe PTS. Furthermore, a venous ulcer scored 4 points whereas all other criteria scored 1, so any patient who had a venous ulcer after DVT would be classified as having severe PTS. This leads to a problem that is also seen in the Widmer and the CEAP classifications, namely, that once a patient develops a venous ulcer, whether or not it heals, he or she will always be classified as having severe PTS. However, a study by Kolbach et al22 investigating the relationship between AVP values and PTS score showed a strong association between severity as assessed by the Brandjes score and higher mean AVP values. Widmer. The Widmer classification was initially developed to grade chronic venous insufficiency, but it also has been utilized in studies of PTS.28 The Widmer score is based purely on clinical signs (Table IV). It was used to diagnose PTS in the Cochrane Systematic Review evaluating compression therapy for treating PTS.29 In the study by Kolbach et al22 investigating the difference between scoring systems, the Widmer classification showed a moderate association with the Brandjes score and the CEAP score (k ¼ 0.52 and k ¼ 0.53, respectively). However, this review also noted that because clinical signs rarely change over time, except with deterioration, the Widmer score would not be ideal to use for measuring the outcome of treatment of PTS. CEAP. The CEAP score was designed to score all chronic venous disease, categorizing patients’ disease according to their clinical signs (C), etiology (E), anatomic
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Table III. Brandjes scoring system4 Subjective criteria Symptoms Spontaneous pain in calf Spontaneous pain in thigh Pain in calf on standing/walking Pain in thigh on standing/walking Edema of foot/calf “Heaviness” of leg Spontaneous pain and pain on walking/standing Impairment of daily activities
Objective criteria Score
Sign
Score
1 1 1 1 1 1 1 1
Calf circumference increased by 1 cm Ankle circumference increased by 1 cm Pigmentation Venectasia Newly formed varicosis Phlebitis Venous ulcer
1 1 1 1 1 1 4
distribution (A), and pathophysiologic condition (P).30 Each limb is categorized according to objective signs into one of seven classes (C0-C6; Table V). A higher class may have any or all of the findings that define a less severe category. Each limb is also scored as to whether it is symptomatic (C0-6,S), or asymptomatic (C0-6,A). The diseased limb is then classified by whether the etiology of the venous disorder is congenital, primary, or secondary (EC, EP, ES). The anatomic sites of venous disease are then denoted by AS for superficial sites, AD for deep sites, and AP for perforating sites. Any or all systems may be involved. For example, AS,D,P indicates disease at all sites. Finally, the pathophysiologic classification indicates whether the venous disease is caused by reflux (PR), obstruction (PO), or both (PR,O). The CEAP classification was used in several studies to diagnose PTS13,15,31-36 and was used to categorize severity of PTS in two of these studies.31,35 Although use of this score has become widespread for chronic venous disease in general, there are difficulties in using this system to score patients with PTS. First, it involves alphabetic components that are not quantifiable, making the patient groups more difficult to compare. Second, certain criteria used to classify clinical class cannot change over time (eg, an active ulcer—CEAP class 6—may heal, but the patient’s disease score can never decrease below class 5). Furthermore, there is no standardization as to which CEAP classification signifies PTS. For example, in a study by Yamaki et al36 into the factors predicting the development of PTS, the CEAP category C0-3S, ES, AS,D,P, PR,O indicated no PTS, and the category C4-6S, ES, AS,D,P, PR,O was used to diagnose PTS. However, other studies used a clinical signs score $3 to diagnose PTS.13,15,32 Other studies used the clinical signs score not only to diagnose but also to classify the severity of PTS,31,35 but not in a standardized way. Therefore, CEAP is not ideal as a PTS scoring system, which would aim to examine the effect of treatment as well as classify severity, and there is not yet an agreed CEAP class that is universally used to diagnose PTS. Venous Clinical Severity Score. As a result of the difficulties posed by the alphabetical elements of the CEAP score and the fact that it is limited in its ability to assess change over time, the Venous Clinical Severity Score (VCSS) was developed,37 which is based on the CEAP classification and attributes scores to nine clinical
Table IV. Widmer scoring system28 Stage 1 2
3
Symptoms Ankle flare Subclinical edema Edema Pigmentation Lipodermatosclerosis White (skin) atrophy Leg ulcer Leg ulcer in the past
Table V. CEAP classification30 Class
Signs
0 1 2 3 4
No visible or palpable signs of venous disease Telangiectases, reticular veins, malleolar flare Varicose veins Edema without skin changes Skin changes ascribed to venous disease (pigmentation, venous eczema, lipodermatosclerosis) Skin changes as above with healed ulceration Skin changes as above with active ulceration
5 6
descriptors, marked from 0 to 3 according to severity. Another 0 to 3 points are allocated according to differences in background conservative therapy (ie, whether elastic stockings were used, and patient compliance with this treatment) to produce a score out of 30 (Table VI). The VCSS was used as an evaluation of endovascular treatment of PTS in a study by Wahlgren et al,38 but there is no standard VCS score to diagnose or grade the severity of PTS. In the study by Kolbach et al22 investigating the differences between the scoring systems, the VCSS showed a poor correlation with all other scoring systems (k ¼ 0.220.41). In addition, a validity study by Meissner et al39 examining the performance characteristics of the VCSS in assessing chronic venous disease showed that although the VCSS showed a good correlation with the CEAP score, there was statistically significant interobserver variability when assessing the component descriptors of pain,
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Table VI. VCSS37 Descriptor
Score ¼ 0
Pain
None
Varicose veins (>4-mm diameter) Venous edema
None None
Score ¼ 1
Score ¼ 2
Score ¼ 3
Occasional, not restricting activity, or requiring analgesia Few, scattered: branch varicosities Evening ankle edema only
Daily, moderate limitation of activity, occasional analgesia Multiple: GS varicose veins confined to calf or thigh Afternoon edema, above ankle Diffuse over most of gaiter distribution (lower third) or recent pigmentation (purple) Moderate cellulitis, involves most of gaiter area (lower third) Medial or lateral, less than lower third of leg 2 3-12
Daily, severe limitation of activities, or requiring regular analgesia Extensive: thigh and calf or GS and LS distribution Morning edema above ankle and requiring change of activities Wider distribution (above lower third) and recent pigmentation Severe cellulitis (lower third and above) or significant venous eczema Entire lower third of leg or more >2 Not healed after 12 months
2-6
>6
Skin pigmentation
None, or focal, low intensity (tan)
Diffuse, but limited in area and old (brown)
Inflammation
None
Induration
None
Mild cellulitis, limited to marginal area around ulcer Focal, circummalleolar (<5 cm) 1 <3
No. of active ulcers Duration of active ulceration, months Diameter of largest ulcer, cm Compressive therapy
0 None
<2
None Not used or noncompliant
Intermittent use of stockings
Wears elastic stocking most days
Full compliance
GS, Great saphenous; LS, lesser saphenous; VCSS, Venous Clinical Severity Score.
Table VII. Comparison of the different PTS scoring systems Criteria
Villalta
Interobserver reliability Association with AVP Association with patient quality-of-life scores Validity Ability to assess PTS severity Ability to assess change over time/with treatment
Yes Yes Yes Yes Yes Yes
Ginsberg
Brandjes
Widmer
VCSS
No evidence Yes Yes Yes No No
No evidence Yes No evidence Yes Yes No
No evidence Yes No evidence Yes Yes No
No evidencea Yes No evidence Yes Yes Yes
AVP, Ambulatory venous pressure; PTS, post-thrombotic syndrome; VCSS, Venous Clinical Severity Score. a Interobserver reliability shown for chronic venous disease only, not for PTS.
inflammation, and pigmentation. Therefore, although the VCSS does address some of the obstacles posed by the CEAP score, it has not yet been used in many studies concerning PTS, and it does not correlate well with existing scoring systems. DISCUSSION An ideal scoring system for PTS should be easy to use, valid, specific, have good interobserver reliability, be acceptable to patients, have a clear association with the pathophysiologic mechanism, and be able to categorize according to disease severity and identify improvement or deterioration in the condition. From the available evidence, only the Villalta score can lay claim to all of these features (Tables VII and VIII). It could be argued that the subjective criteria involved in calculating the score could reduce its reliability, and that perhaps further investigation into inter- and intraobserver reliability would be useful before the score was used in everyday practice. However, the
Villalta score appears to be the most commonly used due to its ease and versatility of use in diagnosis, categorization of severity, and in follow-up. Indeed, in 2008 it was recommended at the International Society on Thrombosis and Haemostasis in Vienna that the Villalta scoring system be utilized in clinical trials as the scoring system of choice for the diagnosis and grading of PTS.40 One caveat affecting all the different scoring systems concerns their validity. Without knowing the exact pathophysiologic process underlying the development of PTS, the scores are only able to measure markers of the disease, such as clinical features, AVPs, and patient symptoms. Thus, no score can be said to be truly valid because there is no clearly defined measurement that can correlate with PTS. Furthermore, only a few studies have examined whether the different scoring systems correlate with the markers of PTS mentioned earlier.6,21,22,25 Although validity testing in this manner ensures that the scoring system is sensitive and specific for the condition for which it has been
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Table VIII. Literature illustrating the properties of the different PTS scoring systems Villalta Interobserver reliability Association with pathophysiology Validity
Diagnosis
Rodger et al20 (2008) Kolbach et al22 (2005) Kahn et al25 (2006) Kahn et al6 (2002) Kahn et al21 (2008) Kolbach et al22 (2005) Kahn et al25 (2006) Prandoni et al2 (1996) van Dongen et al10 (2005) Tick et al11 (2008) Kahn et al12 (2005) Roumen-Klappe et al13 (2009) Kahn et al14 (2005) Roumen-Klappe et al15 (2009) Kahn et al6 (2002) Kahn et al17 (2011) Yes
Categorization of severity Identify change in condition Evaluation of treatment Kahn et al17 (2011) O’Donnell et al18 for PTS (2008) Prandoni19 (2005)
Ginsberg
Brandjes
No evidence Kahn et al25 (2006)
Widmer
VCSS
No evidence No evidence No evidence Kolbach et al22 (2005) Kolbach et al22 Kolbach et al22 (2005) (2005) Kolbach et al22 (2005) Kolbach et al22 Kolbach et al22 (2005) (2005)
Kahn et al25 (2006)
Ginsberg et al5 (2000) Kahn et al24 (2007)
Brandjes et al4 (1997)
Widmer et al28 No evidence (1981) Kolbach et al29 (2003)
No
Yes
Yes
No evidence
No
No
Yes
No evidence
Wahlgren et al38 (2010)
No 23
Ginsberg et al
(2001) No evidence
PTS, Post-thrombotic syndrome; VCSS, Venous Clinical Severity Score.
designed, for conditions such as PTS, where measurable markers of the disease do not always correlate with clinical symptoms, this can give conflicting results. It also could be argued that an assessment of the impact of venous disease on a patient’s quality of life should be part of a PTS score. As demonstrated in the study by Kahn et al,6 patients with PTS have a significantly decreased quality of life, and this in itself is a symptom that contributes to the severity of the condition. Consequently, a quality-of-life questionnaire, such as the VEINES-QOL and VEINES-Sym,41 in combination with the Villalta score, may aid in further clarifying the differences in the categories of severity of the condition and standardize some of the subjective criteria of the Villalta score. CONCLUSIONS PTS is a serious and debilitating condition. Although clinical research to identify the optimal management options has been conducted, the optimal method of defining and classifying PTS has been unclear. From looking at the studies conducted thus far, the frequency with which the Villalta score is used reflects its desirable properties, namely, its ease of use, its flexibility in being used for diagnosis, classification, and evaluation of treatment, and its validity. If the Villalta score were combined with a quality-of-life questionnaire, we believe this would further strengthen the validity of the score. As such, we recommend that the Villalta score combined with a venous disease–specific quality-of-life questionnaire be considered
as the “gold standard” for the diagnosis and classification of PTS.
AUTHOR CONTRIBUTIONS Conception and design: AS, HM, MG, AD Analysis and interpretation: AS, HM, MG, AD Data collection: AS, HM Writing the article: AS, HM Critical revision of the article: AS, HM, MG, AD Final approval of the article: HM, MG, AD Statistical analysis: AS, HM, MG, AD Obtained funding: Not applicable Overall responsibility: AS, AD REFERENCES 1. Salzmann E, Hirsh J, Marder V. The epidemiology, pathogenesis, and natural history of venous thrombosis. In: Colman RW, editor. Hemostasis and thrombosis: basic principles and clinical practice. Philadelphia: Lippincott; 1993. p. 1346-66. 2. Prandoni P, Lensing AW, Cogo A, Cuppini S, Villalta S, Carta M, et al. The long-term clinical course of acute deep venous thrombosis. Ann Intern Med 1996;125:1-7. 3. Prandoni P, Villalta S, Bagatella P, Rossi L, Marchiori A, Piccioli A, et al. The clinical course of deep-vein thrombosis. Prospective longterm follow-up of 528 symptomatic patients. Haematologica 1997;82:423-8. 4. Brandjes DP, Buller HR, Heijboer H, Huisman MV, de Rijk M, Jagt H, et al. Randomised trial of effect of compression stockings in patients with symptomatic proximal-vein thrombosis. Lancet 1997;349:759-62.
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5. Ginsberg JS, Turkstra F, Buller HR, MacKinnon B, Magier D, Hirsh J. Postthrombotic syndrome after hip or knee arthroplasty: a crosssectional study. Arch Intern Med 2000;160:669-72. 6. Kahn SR, Hirsch A, Shrier I. Effect of postthrombotic syndrome on health-related quality of life after deep venous thrombosis. Arch Intern Med 2002;162:1144-8. 7. Bergqvist D, Jendteg S, Johansen L, Persson U, Odegaard K. Cost of long-term complications of deep venous thrombosis of the lower extremities: an analysis of a defined patient population in Sweden. Ann Intern Med 1997;126:454-7. 8. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009;339:b2535. 9. Villalta S, Bagatella P, Piccioli A, Lensing AW, Prins MH, Prandoni P. Assessment of validity and reproducibility of a clinical scale for the postthrombotic syndrome (abstract). Haemostasis 1994;24:158a. 10. van Dongen CJ, Prandoni P, Frulla M, Marchiori A, Prins MH, Hutten BA. Relation between quality of anticoagulant treatment and the development of the postthrombotic syndrome. J Thromb Haemost 2005;3:939-42. 11. Tick LW, Kramer MH, Rosendaal FR, Faber WR, Doggen CJ. Risk factors for post-thrombotic syndrome in patients with a first deep venous thrombosis. J Thromb Haemost 2008;6:2075-81. 12. Kahn SR, Ducruet T, Lamping DL, Arsenault L, Miron MJ, Roussin A, et al. Prospective evaluation of health-related quality of life in patients with deep venous thrombosis. Arch Intern Med 2005;165:1173-8. 13. Roumen-Klappe EM, Janssen MC, Van Rossum J, Holewijn S, Van Bokhoven MM, Kaasjager K, et al. Inflammation in deep vein thrombosis and the development of post-thrombotic syndrome: a prospective study. J Thromb Haemost 2009;7:582-7. 14. Kahn SR, Kearon C, Julian JA, Mackinnon B, Kovacs MJ, Wells P, et al. Predictors of the post-thrombotic syndrome during long-term treatment of proximal deep vein thrombosis. J Thromb Haemost 2005;3:718-23. 15. Roumen-Klappe EM, den Heijer M, van Rossum J, Wollersheim H, van der Vleuten C, Thien T, et al. Multilayer compression bandaging in the acute phase of deep-vein thrombosis has no effect on the development of the post-thrombotic syndrome. J Thromb Thrombolysis 2009;27:400-5. 16. Kahn SR, Shrier I, Julian JA, Ducruet T, Arsenault L, Miron MJ, et al. Determinants and time course of the postthrombotic syndrome after acute deep venous thrombosis. Ann Intern Med 2008;149:698-707. 17. Kahn SR, Shrier I, Shapiro S, Houweling AH, Hirsch AM, Reid RD, et al. Six-month exercise training program to treat post-thrombotic syndrome: a randomized controlled two-centre trial. CMAJ 2011;183:37-44. 18. O’Donnell MJ, McRae S, Kahn SR, Julian JA, Kearon C, Mackinnon B, et al. Evaluation of a venous-return assist device to treat severe post-thrombotic syndrome (VENOPTS). A randomized controlled trial. Thromb Haemost 2008;99:623-9. 19. Prandoni P. Elastic stockings, hydroxyethylrutosides or both for the treatment of post-thrombotic syndrome. Thromb Haemost 2005;93: 183-5. 20. Rodger MA, Kahn SR, Le Gal G, Solymoss S, Chagnon I, Anderson DR, et al. Inter-observer reliability of measures to assess the post-thrombotic syndrome. Thromb Haemost 2008;100:164-6. 21. Kahn SR, Shbaklo H, Lamping DL, Holcroft CA, Shrier I, Miron MJ, et al. Determinants of health-related quality of life during the 2 years following deep vein thrombosis. J Thromb Haemost 2008;6:1105-12. 22. Kolbach DN, Neumann HA, Prins MH. Definition of the postthrombotic syndrome, differences between existing classifications. Eur J Vasc Endovasc Surg 2005;30:404-14. 23. Ginsberg JS, Hirsh J, Julian J, Vander LaandeVries M, Magier D, MacKinnon B, et al. Prevention and treatment of postphlebitic syndrome: results of a 3-part study. Arch Intern Med 2001;161: 2105-9.
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24. Kahn SR, Shbaklo H, Shapiro S, Wells PS, Kovacs MJ, Rodger MA, et al. Effectiveness of compression stockings to prevent the postthrombotic syndrome (the SOX Trial and Bio-SOX biomarker substudy): a randomized controlled trial. BMC Cardiovasc Disord 2007;7:21. 25. Kahn SR, Desmarais S, Ducruet T, Arsenault L, Ginsberg JS. Comparison of the Villalta and Ginsberg clinical scales to diagnose the post-thrombotic syndrome: correlation with patient-reported disease burden and venous valvular reflux. J Thromb Haemost 2006;4:907-8. 26. Kakkar VV, Lawrence D. Hemodynamic and clinical assessment after therapy for acute deep vein thrombosis. A prospective study. Am J Surg 1985;150(4A):54-63. 27. Brakkee A, Kuiper J. The influence of compressive stockings on the haemodynamics in the lower extremities. Phlebology 1988;3:147-53. 28. Widmer L, Stathelin H, Nissen C. Sd. Venen-, Arterien-, Krankheiten, koronaire Herzkrankhei bei berufstatigen. Bern: Verlag Hans Huber; 1981. 29. Kolbach DN, Sandbrink MW, Neumann HA, Prins MH. Compression therapy for treating stage I and II (Widmer) post-thrombotic syndrome. Cochrane Database Syst Rev 2003;4:CD004177. 30. Porter JM, Moneta G. An International Consensus Committee on Chronic Venous Disease. Reporting standards in venous disease: an update. J Vasc Surg 1988;8:172-81. 31. Haenen JH, Janssen MC, van Langen H, van Asten WN, Wollersheim H, van’t Hof MA, et al. The postthrombotic syndrome in relation to venous hemodynamics, as measured by means of duplex scanning and strain-gauge plethysmography. J Vasc Surg 1999;29: 1071-6. 32. Roumen-Klappe EM, den Heijer M, Janssen MC, van der Vleuten C, Thien T, Wollersheim H. The post-thrombotic syndrome: incidence and prognostic value of non-invasive venous examinations in a six-year follow-up study. Thromb Haemost 2005;94:825-30. 33. Aschwanden M, Jeanneret C, Koller MT, Thalhammer C, Bucher HC, Jaeger KA. Effect of prolonged treatment with compression stockings to prevent post-thrombotic sequelae: a randomized controlled trial. J Vasc Surg 2008;47:1015-21. 34. Yamaki T, Nozaki M, Sakurai H, Kikuchi Y, Soejima K, Kono T, et al. Prognostic impact of calf muscle near-infrared spectroscopy in patients with a first episode of deep vein thrombosis. J Thromb Haemost 2009;7:1506-13. 35. Lindow C, Mumme A, Asciutto G, Strohmann B, Hummel T, Geier B. Long-term results after transfemoral venous thrombectomy for iliofemoral deep venous thrombosis. Eur J Vasc Endovasc Surg 2010;40: 134-8. 36. Yamaki T, Hamahata A, Soejima K, Kono T, Nozaki M, Sakurai H. Factors predicting development of post-thrombotic syndrome in patients with a first episode of deep vein thrombosis: preliminary report. Eur J Vasc Endovasc Surg 2011;41:126-33. 37. Rutherford RB, Padberg FT Jr, Comerota AJ, Kistner RL, Meissner MH, Moneta GL. Venous severity scoring: an adjunct to venous outcome assessment. J Vasc Surg 2000;31:1307-12. 38. Wahlgren CM, Wahlberg E, Olofsson P. Endovascular treatment in postthrombotic syndrome. Vasc Endovasc Surg 2010;44:356-60. 39. Meissner MH, Natiello C, Nicholls SC. Performance characteristics of the venous clinical severity score. Vasc Surg 2002;36:889-95. 40. Kahn SR, Partsch H, Vedantham S, Prandoni P, Kearson C. Definition of post-thrombotic syndrome of the leg for use in clinical investigations: a recommendation for standardisation. J Thromb Haemost 2009;7:879-83. 41. Lamping DL, Schroter S, Kurz X, Kahn SR, Abenhaim L. Evaluating outcomes in chronic venous disorders of the leg: development of a scientifically rigorous patient-reported measure of symptoms and quality of life. J Vasc Surg 2003;37:410-9.
Submitted Mar 14, 2012; accepted Sep 1, 2012.
Deep vein thrombosis (DVT) of the lower limbs is both a common and a serious disease, with an estimated incidence of 1 per 1000 people per year.1 It can have a clear precipitant, such as surgery, malignancy, or inherited coagulation disorders, or occur spontaneously. A number of complications can follow DVT. The incidence and outcomes of acute complications such as pulmonary embolism are well reported, but post-thrombotic syndrome (PTS) is less well understood. This is a chronic condition, occurring in at least one third of patients who have a DVT.2 It may be associated with leg pain and heaviness, edema, hyperpigmentation, lipodermatosclerosis, and venous ulceration, occurring to varying degrees in different patients. The pathophysiology underlying PTS is thought to be sustained venous hypertension, resulting from obstruction to venous flow, vein valvular incompetence, or a combination. As there is a considerable degree of overlap between the acute symptoms resulting from a DVT and those of PTS, there is a minimum time period (ranging from 6 months to 2 years in various studies3-5) before
From the Academic Section of Vascular Surgery, Department of Surgery & Cancer, Imperial College School of Medicine, Charing Cross Hospital. Author conflict of interest: none. Reprint requests: Professor Alun H. Davies, Academic Section of Vascular Surgery, Department of Surgery & Cancer, Imperial College School of Medicine, Charing Cross Hospital, Fulham Palace Road, London, W6 8RF, United Kingdom (e-mail: [email protected]). The editors and reviewers of this article have no relevant financial relationships to disclose per the JVS policy that requires reviewers to decline review of any manuscript for which they may have a conflict of interest. 0741-5214/$36.00 Copyright Ó 2013 by the Society for Vascular Surgery. http://dx.doi.org/10.1016/j.jvs.2012.09.011
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the condition is diagnosed. Patients with PTS have a significantly decreased quality of life6 and the condition can result in a substantial psychological and economic burden.7 However, although there is a large body of research concerning the natural history and treatment options of acute DVT, there is less evidence on the diagnosis and management of PTS. One of the reasons often cited for this is the lack of a clear gold standard definition of PTS. Instead, several scoring systems are used to both diagnose the condition and classify its severity. This review aims to describe the main scoring systems, illustrate how they have been used in studies investigating PTS, and outline whether one scoring system demonstrates advantages over the others. METHODS This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.8 The relevant studies and reviews were found through systematic searches of PubMed (1948 to September 2011). The search terms used were “postthrombotic syndrome,” “postthrombotic syndrome,” “post-phlebitic syndrome,” and “postphlebitic syndrome.” A manual reference list search was also carried out to identify further studies that would be appropriate for inclusion. The titles of the search results were screened with human and English language limits to identify the studies to be included. The abstracts and full text of these were then examined by two of the authors (A.S., H.M.) to identify those relevant to this review’s scope, namely, those that referred to a PTS scoring system. Articles concerning the upper limb and children were excluded. All other articles including prospective and
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Fig 1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) diagram. Summary of search strategy and results of literature review.
retrospective studies, human participants, data related to adult (>18 years) patients, and lower limbs were included. Once the relevant articles were obtained, a list of the main PTS scoring systems in use was made. Each scoring system was then assessed for validity of use according to specific criteria, including interobserver reliability, association with ambulatory venous pressures (AVPs), ability to assess severity of PTS, ability to assess the change in condition over time, and association with patient-reported symptom severity. RESULTS The search strategy, carried out as described in Fig 1, resulted in 37 publications that fulfilled the inclusion criteria. Villalta. The Villalta score is a disease score specific for PTS.9 It can be used to both diagnose and categorize the severity of the condition. It was developed in a crosssectional study of 100 patients who were assessed 6 to 36 months after DVT. Points are given for five symptoms
(pain, cramps, heaviness, paresthesia, pruritus) and six clinical signs (pretibial edema, skin induration, hyperpigmentation, redness, venous ectasia, pain on calf compression). Points are given for each of these 11 descriptors according to severity (Table I), ranging from 0 for not present to 3 for severe. Furthermore, if a venous ulcer was present, the severity of the condition was classified as severe, regardless of the presence or absence of other signs or symptoms. The patient was diagnosed as having PTS if the Villalta score was $5 or if a venous ulcer was present. A score of 5-9 signifies mild disease, 10-14 moderate disease, and $15 severe disease. The Villalta score was used in several studies to diagnose PTS.2,10-15 Five studies used the Villalta score as originally described, with scores >5 confirming the diagnosis of PTS and a score >14 denoting severe PTS,2,10,12-15 and one study used a modified Villalta score, giving a final score out of 9, with 4 being diagnostic and 7 the threshold for severe PTS.11 When a diagnosis of PTS is made using the Villalta score, only one assessment giving a score >5 is
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Table I. Villalta’s PTS score9 Symptoms/clinical signs Symptoms Pain Cramps Heaviness Paresthesia Pruritus Clinical signs Pretibial edema Skin induration Hyperpigmentation Redness Venous ectasia Pain on calf compression Venous ulcer
None
Table II. Uses of the Villalta score in various studies Mild
Moderate
Severe Author (year)
0 0 0 0 0
points points points points points
1 1 1 1 1
point point point point point
2 2 2 2 2
points points points points points
3 3 3 3 3
points points points points points
0 points 0 points 0 points 0 points 0 points 0 points Absent
1 1 1 1 1 1
point point point point point point
2 2 2 2 2 2
points points points points points points
3 points 3 points 3 points 3 points 3 points 3 points Present
PTS, Post-thrombotic syndrome.
required, in contrast to certain other scores, which require multiple assessments, with a set time interval in between. The Villata score has also been used as a continuous measurement for longer-term follow-up3,16 to grade the severity of the condition6,17 and to assess the effectiveness of treatments (Table II).17-19 The score has also been shown to yield reliable consistent results, whether used by physicians9 or by other health professionals trained in using the scale.20 As such, use of the Villalta score can be justified, whether in clinic settings to monitor the progress of patients or in studies assessing the impact of treatment. In addition, Villalta scores in patients with PTS appear to correlate with patient-perceived quality of life as well as with clinical measurements thought to be related to the pathophysiology underlying PTS, thus suggesting the Villalta score is a valid scale for clinical use.6,21,22 Two studies assessed both the generic and the disease-specific healthrelated quality of life after DVT.6,21 They showed that although quality-of-life scores tended to improve from baseline after DVT, patients who developed PTS had significantly worse disease-specific quality-of-life scores.6,21 These lower scores were not present on the generic qualityof-life scores, thus attributing the difference to the condition. The results of the two studies, showing how the Villalta scores correlate with quality-of-life scores, are summarized in Fig 2.6,21 In these two studies, the Villalta score was used to categorize PTS into mild, moderate, and severe (Table I). The Venous Insufficiency Epidemiological and Economic Study/Quality of Life (VEINES-QOL) and the Venous Insufficiency Epidemiological and Economic Study/Symptoms (VEINES-Sym) are patient-reported outcome scores that can be computed from a 25-item questionnaire. The items cover symptoms (heavy legs, aching legs, swelling, night cramps, heat or burning sensation, restless legs, throbbing, itching, tingling sensation, leg pain), limitations in daily activities, change over the past year, and psychological impact. The VEINES-QOL summary score aims to measure the overall impact of venous disease on a patient’s life. The VEINES-Sym score
No. enrolled (completed follow-up)
355 (245) Prandoni et al2 (1996) 300 (244) Van Dongen et al10 (2005) 11 1916 (1668) Tick et al (2008) 359 Kahn et al12 (2005) 116 (110) Roumen-Klappe et al13 (2009) 145 Kahn et al14 (2005) 69 Roumen-Klappe et al15 (2009) 41 Kahn et al6 (2002) 43 (39) Kahn et al17 (2011) 528 Prandoni et al3 (1997) 387 (260) Kahn et al16 (2008) 43 (39) Kahn et al17 (2011) 32 (26) O’Donnell et al18 (2008) 19 120 Prandoni et al (2005)
Application Diagnosis Diagnosis Diagnosis Diagnosis Diagnosis Diagnosis Diagnosis Classify severity Classify severity Long-term follow-up Long-term follow-up Evaluation of treatment Evaluation of treatment Evaluation of treatment
is a subscale that measures the specific impact of symptoms on daily life. In both measures, lower scores indicate lower quality of life. The data from Kahn et al6 have remained unchanged. The data from Kahn et al21 have had the results listed for mild PTS and moderate PTS amalgamated but otherwise unprocessed. In looking at the differences between existing classification systems, Kolbach et al22 examined the association between AVP (measured via invasive methods) and the scores obtained from the various scoring systems. In this study, the Villalta score was one of the systems with a strong association with a high AVP value. However, there was a caveat to this conclusion; there was a considerable degree of overlap in AVPs in the different clinical severities of PTS, indicating that there is not a simplistic linear relationship between venous hypertension and PTS. In the absence of a gold standard with which to define the PTS, the wide spectrum of disease severity, and hence the difficulty in assessing validity of the various scoring systems, these surrogate measures (health-related quality of life and numerical measurements of pathophysiologic markers of the disease) suggest that the Villalta score correlates with the clinical and physiologic markers of the disease. Ginsberg. The Ginsberg score was designed in a crosssectional study looking at PTS developing after hip or knee arthroplasty.5 It diagnosed patients as having PTS if the patient reported leg pain and swelling of a chronic nature (daily, for a period of at least 1 month), typical in character (aggravated by prolonged standing, improved by leg elevation), occurring at least 6 months after the initial DVT. Patients could be diagnosed with PTS only if they had both leg pain and swelling and if there was objective evidence of valvular incompetence. The presence of persistent occlusion was not included. The Ginsberg score was used in a study evaluating the efficacy of graduated
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None Mild/Moderate PTS Severe PTS 70
60
Mean Scores
50
40
30
20
10
0 Mean VEINES-QOL (2002)
Mean VEINES-Sym (2002)
Mean VEINES-QOL (2008)
Mean VEINES-Sym (2008)
Quality of Life Scores
Fig 2. Graph demonstrating quality-of-life scores in patients with different degrees of post-thrombotic syndrome (PTS).6,21
compression stockings in preventing and in treating PTS.23 It also will be used to diagnose PTS in the SOX trial, which was designed to investigate the effectiveness of compression stockings in preventing PTS.24 Kahn et al25 compared the Ginsberg and Villalta scales with respect to the healthrelated quality of life of patients and with venous valvular reflux (as a physiologic indicator of chronic venous disease). In this study, they found that when the Villalta score was used, almost five times as many patients were diagnosed with PTS at 1 year than when the Ginsberg score was used. They also found that patients diagnosed with the condition when the Ginsberg score was used had higher mean numeric Villalta scores and lower quality-oflife scores, suggesting that the Ginsberg scale only identifies those patients with more severe disease. Furthermore, this score does not rate the severity of the condition and may not include patients with predominantly occlusive deep venous disease. Brandjes. The Brandjes score was developed as part of a trial looking at the effect of compression stockings on patients with symptomatic proximal DVT.4 In a manner similar to the Villalta score, points are given for a number of subjective and objective criteria (Table III). These criteria were chosen from combined components of other scoring systems,26,27 and patients were classified as having PTS based on their score over two consecutive visits, 3 months apart. A score of 3 or higher (including one objective criterion) diagnosed mild-moderate PTS, whereas a score of 4 or more from a list of more severe
subjective and objective criteria defined severe PTS. Furthermore, a venous ulcer scored 4 points whereas all other criteria scored 1, so any patient who had a venous ulcer after DVT would be classified as having severe PTS. This leads to a problem that is also seen in the Widmer and the CEAP classifications, namely, that once a patient develops a venous ulcer, whether or not it heals, he or she will always be classified as having severe PTS. However, a study by Kolbach et al22 investigating the relationship between AVP values and PTS score showed a strong association between severity as assessed by the Brandjes score and higher mean AVP values. Widmer. The Widmer classification was initially developed to grade chronic venous insufficiency, but it also has been utilized in studies of PTS.28 The Widmer score is based purely on clinical signs (Table IV). It was used to diagnose PTS in the Cochrane Systematic Review evaluating compression therapy for treating PTS.29 In the study by Kolbach et al22 investigating the difference between scoring systems, the Widmer classification showed a moderate association with the Brandjes score and the CEAP score (k ¼ 0.52 and k ¼ 0.53, respectively). However, this review also noted that because clinical signs rarely change over time, except with deterioration, the Widmer score would not be ideal to use for measuring the outcome of treatment of PTS. CEAP. The CEAP score was designed to score all chronic venous disease, categorizing patients’ disease according to their clinical signs (C), etiology (E), anatomic
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Table III. Brandjes scoring system4 Subjective criteria Symptoms Spontaneous pain in calf Spontaneous pain in thigh Pain in calf on standing/walking Pain in thigh on standing/walking Edema of foot/calf “Heaviness” of leg Spontaneous pain and pain on walking/standing Impairment of daily activities
Objective criteria Score
Sign
Score
1 1 1 1 1 1 1 1
Calf circumference increased by 1 cm Ankle circumference increased by 1 cm Pigmentation Venectasia Newly formed varicosis Phlebitis Venous ulcer
1 1 1 1 1 1 4
distribution (A), and pathophysiologic condition (P).30 Each limb is categorized according to objective signs into one of seven classes (C0-C6; Table V). A higher class may have any or all of the findings that define a less severe category. Each limb is also scored as to whether it is symptomatic (C0-6,S), or asymptomatic (C0-6,A). The diseased limb is then classified by whether the etiology of the venous disorder is congenital, primary, or secondary (EC, EP, ES). The anatomic sites of venous disease are then denoted by AS for superficial sites, AD for deep sites, and AP for perforating sites. Any or all systems may be involved. For example, AS,D,P indicates disease at all sites. Finally, the pathophysiologic classification indicates whether the venous disease is caused by reflux (PR), obstruction (PO), or both (PR,O). The CEAP classification was used in several studies to diagnose PTS13,15,31-36 and was used to categorize severity of PTS in two of these studies.31,35 Although use of this score has become widespread for chronic venous disease in general, there are difficulties in using this system to score patients with PTS. First, it involves alphabetic components that are not quantifiable, making the patient groups more difficult to compare. Second, certain criteria used to classify clinical class cannot change over time (eg, an active ulcer—CEAP class 6—may heal, but the patient’s disease score can never decrease below class 5). Furthermore, there is no standardization as to which CEAP classification signifies PTS. For example, in a study by Yamaki et al36 into the factors predicting the development of PTS, the CEAP category C0-3S, ES, AS,D,P, PR,O indicated no PTS, and the category C4-6S, ES, AS,D,P, PR,O was used to diagnose PTS. However, other studies used a clinical signs score $3 to diagnose PTS.13,15,32 Other studies used the clinical signs score not only to diagnose but also to classify the severity of PTS,31,35 but not in a standardized way. Therefore, CEAP is not ideal as a PTS scoring system, which would aim to examine the effect of treatment as well as classify severity, and there is not yet an agreed CEAP class that is universally used to diagnose PTS. Venous Clinical Severity Score. As a result of the difficulties posed by the alphabetical elements of the CEAP score and the fact that it is limited in its ability to assess change over time, the Venous Clinical Severity Score (VCSS) was developed,37 which is based on the CEAP classification and attributes scores to nine clinical
Table IV. Widmer scoring system28 Stage 1 2
3
Symptoms Ankle flare Subclinical edema Edema Pigmentation Lipodermatosclerosis White (skin) atrophy Leg ulcer Leg ulcer in the past
Table V. CEAP classification30 Class
Signs
0 1 2 3 4
No visible or palpable signs of venous disease Telangiectases, reticular veins, malleolar flare Varicose veins Edema without skin changes Skin changes ascribed to venous disease (pigmentation, venous eczema, lipodermatosclerosis) Skin changes as above with healed ulceration Skin changes as above with active ulceration
5 6
descriptors, marked from 0 to 3 according to severity. Another 0 to 3 points are allocated according to differences in background conservative therapy (ie, whether elastic stockings were used, and patient compliance with this treatment) to produce a score out of 30 (Table VI). The VCSS was used as an evaluation of endovascular treatment of PTS in a study by Wahlgren et al,38 but there is no standard VCS score to diagnose or grade the severity of PTS. In the study by Kolbach et al22 investigating the differences between the scoring systems, the VCSS showed a poor correlation with all other scoring systems (k ¼ 0.220.41). In addition, a validity study by Meissner et al39 examining the performance characteristics of the VCSS in assessing chronic venous disease showed that although the VCSS showed a good correlation with the CEAP score, there was statistically significant interobserver variability when assessing the component descriptors of pain,
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Table VI. VCSS37 Descriptor
Score ¼ 0
Pain
None
Varicose veins (>4-mm diameter) Venous edema
None None
Score ¼ 1
Score ¼ 2
Score ¼ 3
Occasional, not restricting activity, or requiring analgesia Few, scattered: branch varicosities Evening ankle edema only
Daily, moderate limitation of activity, occasional analgesia Multiple: GS varicose veins confined to calf or thigh Afternoon edema, above ankle Diffuse over most of gaiter distribution (lower third) or recent pigmentation (purple) Moderate cellulitis, involves most of gaiter area (lower third) Medial or lateral, less than lower third of leg 2 3-12
Daily, severe limitation of activities, or requiring regular analgesia Extensive: thigh and calf or GS and LS distribution Morning edema above ankle and requiring change of activities Wider distribution (above lower third) and recent pigmentation Severe cellulitis (lower third and above) or significant venous eczema Entire lower third of leg or more >2 Not healed after 12 months
2-6
>6
Skin pigmentation
None, or focal, low intensity (tan)
Diffuse, but limited in area and old (brown)
Inflammation
None
Induration
None
Mild cellulitis, limited to marginal area around ulcer Focal, circummalleolar (<5 cm) 1 <3
No. of active ulcers Duration of active ulceration, months Diameter of largest ulcer, cm Compressive therapy
0 None
<2
None Not used or noncompliant
Intermittent use of stockings
Wears elastic stocking most days
Full compliance
GS, Great saphenous; LS, lesser saphenous; VCSS, Venous Clinical Severity Score.
Table VII. Comparison of the different PTS scoring systems Criteria
Villalta
Interobserver reliability Association with AVP Association with patient quality-of-life scores Validity Ability to assess PTS severity Ability to assess change over time/with treatment
Yes Yes Yes Yes Yes Yes
Ginsberg
Brandjes
Widmer
VCSS
No evidence Yes Yes Yes No No
No evidence Yes No evidence Yes Yes No
No evidence Yes No evidence Yes Yes No
No evidencea Yes No evidence Yes Yes Yes
AVP, Ambulatory venous pressure; PTS, post-thrombotic syndrome; VCSS, Venous Clinical Severity Score. a Interobserver reliability shown for chronic venous disease only, not for PTS.
inflammation, and pigmentation. Therefore, although the VCSS does address some of the obstacles posed by the CEAP score, it has not yet been used in many studies concerning PTS, and it does not correlate well with existing scoring systems. DISCUSSION An ideal scoring system for PTS should be easy to use, valid, specific, have good interobserver reliability, be acceptable to patients, have a clear association with the pathophysiologic mechanism, and be able to categorize according to disease severity and identify improvement or deterioration in the condition. From the available evidence, only the Villalta score can lay claim to all of these features (Tables VII and VIII). It could be argued that the subjective criteria involved in calculating the score could reduce its reliability, and that perhaps further investigation into inter- and intraobserver reliability would be useful before the score was used in everyday practice. However, the
Villalta score appears to be the most commonly used due to its ease and versatility of use in diagnosis, categorization of severity, and in follow-up. Indeed, in 2008 it was recommended at the International Society on Thrombosis and Haemostasis in Vienna that the Villalta scoring system be utilized in clinical trials as the scoring system of choice for the diagnosis and grading of PTS.40 One caveat affecting all the different scoring systems concerns their validity. Without knowing the exact pathophysiologic process underlying the development of PTS, the scores are only able to measure markers of the disease, such as clinical features, AVPs, and patient symptoms. Thus, no score can be said to be truly valid because there is no clearly defined measurement that can correlate with PTS. Furthermore, only a few studies have examined whether the different scoring systems correlate with the markers of PTS mentioned earlier.6,21,22,25 Although validity testing in this manner ensures that the scoring system is sensitive and specific for the condition for which it has been
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Table VIII. Literature illustrating the properties of the different PTS scoring systems Villalta Interobserver reliability Association with pathophysiology Validity
Diagnosis
Rodger et al20 (2008) Kolbach et al22 (2005) Kahn et al25 (2006) Kahn et al6 (2002) Kahn et al21 (2008) Kolbach et al22 (2005) Kahn et al25 (2006) Prandoni et al2 (1996) van Dongen et al10 (2005) Tick et al11 (2008) Kahn et al12 (2005) Roumen-Klappe et al13 (2009) Kahn et al14 (2005) Roumen-Klappe et al15 (2009) Kahn et al6 (2002) Kahn et al17 (2011) Yes
Categorization of severity Identify change in condition Evaluation of treatment Kahn et al17 (2011) O’Donnell et al18 for PTS (2008) Prandoni19 (2005)
Ginsberg
Brandjes
No evidence Kahn et al25 (2006)
Widmer
VCSS
No evidence No evidence No evidence Kolbach et al22 (2005) Kolbach et al22 Kolbach et al22 (2005) (2005) Kolbach et al22 (2005) Kolbach et al22 Kolbach et al22 (2005) (2005)
Kahn et al25 (2006)
Ginsberg et al5 (2000) Kahn et al24 (2007)
Brandjes et al4 (1997)
Widmer et al28 No evidence (1981) Kolbach et al29 (2003)
No
Yes
Yes
No evidence
No
No
Yes
No evidence
Wahlgren et al38 (2010)
No 23
Ginsberg et al
(2001) No evidence
PTS, Post-thrombotic syndrome; VCSS, Venous Clinical Severity Score.
designed, for conditions such as PTS, where measurable markers of the disease do not always correlate with clinical symptoms, this can give conflicting results. It also could be argued that an assessment of the impact of venous disease on a patient’s quality of life should be part of a PTS score. As demonstrated in the study by Kahn et al,6 patients with PTS have a significantly decreased quality of life, and this in itself is a symptom that contributes to the severity of the condition. Consequently, a quality-of-life questionnaire, such as the VEINES-QOL and VEINES-Sym,41 in combination with the Villalta score, may aid in further clarifying the differences in the categories of severity of the condition and standardize some of the subjective criteria of the Villalta score. CONCLUSIONS PTS is a serious and debilitating condition. Although clinical research to identify the optimal management options has been conducted, the optimal method of defining and classifying PTS has been unclear. From looking at the studies conducted thus far, the frequency with which the Villalta score is used reflects its desirable properties, namely, its ease of use, its flexibility in being used for diagnosis, classification, and evaluation of treatment, and its validity. If the Villalta score were combined with a quality-of-life questionnaire, we believe this would further strengthen the validity of the score. As such, we recommend that the Villalta score combined with a venous disease–specific quality-of-life questionnaire be considered
as the “gold standard” for the diagnosis and classification of PTS.
AUTHOR CONTRIBUTIONS Conception and design: AS, HM, MG, AD Analysis and interpretation: AS, HM, MG, AD Data collection: AS, HM Writing the article: AS, HM Critical revision of the article: AS, HM, MG, AD Final approval of the article: HM, MG, AD Statistical analysis: AS, HM, MG, AD Obtained funding: Not applicable Overall responsibility: AS, AD REFERENCES 1. Salzmann E, Hirsh J, Marder V. The epidemiology, pathogenesis, and natural history of venous thrombosis. In: Colman RW, editor. Hemostasis and thrombosis: basic principles and clinical practice. Philadelphia: Lippincott; 1993. p. 1346-66. 2. Prandoni P, Lensing AW, Cogo A, Cuppini S, Villalta S, Carta M, et al. The long-term clinical course of acute deep venous thrombosis. Ann Intern Med 1996;125:1-7. 3. Prandoni P, Villalta S, Bagatella P, Rossi L, Marchiori A, Piccioli A, et al. The clinical course of deep-vein thrombosis. Prospective longterm follow-up of 528 symptomatic patients. Haematologica 1997;82:423-8. 4. Brandjes DP, Buller HR, Heijboer H, Huisman MV, de Rijk M, Jagt H, et al. Randomised trial of effect of compression stockings in patients with symptomatic proximal-vein thrombosis. Lancet 1997;349:759-62.
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Submitted Mar 14, 2012; accepted Sep 1, 2012.