Post-thrombotic syndrome in children: a systematic review of frequency of occurrence, validity of outcome measures, and prognostic factors

Abstract

Background: Post-thrombotic syndrome is a manifestation of chronic venous insufficiency following deep venous thrombosis. This systematic review was conducted to critically evaluate pediatric evidence on frequency of occurrence, validity of outcome measures, and prognostic indicators of post-thrombotic syndrome.

Design and methods: A comprehensive literature search of original reports revealed 19 eligible studies, totaling 977 patients with upper/lower extremity deep venous thrombosis. Calculated weighted mean frequency of post-thrombotic syndrome was 26% (95% confidence interval: 23-28%) overall, and differed significantly by prospective/non-prospective analysis and use/non-use of a standardized outcome measure.

Results: Standardized post-thrombotic syndrome outcome measures included an adaptation of the Villalta scale, the Clinical-Etiologic-Anatomic-Pathologic classification, and the Manco-Johnson instrument. Data on validity were reported only for the Manco-Johnson instrument. No publications on post-thrombotic syndrome-related quality of life outcomes were identified. Candidate prognostic factors for post-thrombotic syndrome in prospective studies included use/non-use of thrombolysis and plasma levels of factor VIII activity and D-dimer.

Conclusions: Given that affected children must endure chronic sequelae for many decades, it is imperative that future collaborative pediatric prospective cohort studies and trials assess as key objectives and outcomes the incidence, severity, prognostic indicators, and health impact of post-thrombotic syndrome, using validated measures.

Figure 1.

Flow chart of search results and their distribution by category of publication, indicating both included and excluded reports.

Figure 2.

Components of standardized outcome measures for PTS employed in pediatric studies, including the modified Villalta scoring system, the Manco-Johnson instrument, and Basic CEAP. (A) Modified Villalta Scale., (B) Manco-Johnson instrument., (C) Basic Clinical-Etiologic-Anatomic-Pathophysiologic (CEAP) classification of chronic lower extremity venous disease, as used in van Ommen et al.

Figure 3.

Manco-Johnson instrument.