Validation of Post-Thrombotic Syndrome Outcome Scale for Children with Extremity and Non-Extremity Venous Thromboembolism (VTE).

Post-thrombotic syndrome is increasingly diagnosed in children with VTE. Unlike adults, the clinical spectrum of PTS is not restricted to extremities but extends to non-extremity manifestations as well. In order to incorporate the entire spectrum of PTS in children, an expanded PTS assessment scale (EPTSAS) was developed based on critical evaluation of chronic consequences of extremity and non-extremity VTEs that could have been caused directly due to intravenous hypertension (Table 1). EPTSAS included signs and symptoms of PTS and divided them as major and minor criteria. Each component of scale was given a score of 0,1 or 2 based on its' presence/absence and the severity. Depending on the total score in both major and minor category, the severity of PTS was classified as “No PTS”, “PTS likely” and “PTS present” (A. Sharathkumar et al, Blood (ASH Annual Meeting Abstracts), 2007; 110: 3196). In a retrospective cohort of children with VTE, the sensitivity, specificity and inter-observer agreement for the diagnosis of PTS was 100%, 88.5% and 66% (interpreted as “good”) respectively (A. Sharathkumar, ISTH, SSC Subcommittee meeting, 2008). In present study, we evaluated the validity of EPTSAS prospectively.

All the consecutive children (age<19 years) who were seen in hematology clinic at Riley Children's Hospital with a confirmed history of VTE and minimal follow up of 6 months were eligible to participate in the study. Clinical data about the patient demographics and VTE characteristics was collected. Severity of PTS was diagnosed using an established PTS assessment scale, “Kuhle's PTS scale”. Validity of EPTSAS was compared against Kuhle's scale. Two independent investigators assessed the severity of PTS using EPTSAS to evaluate an inter-observer agreement.

A total of 25 patients (26 VTE events) were enrolled in a study over a 15-month period (March 2009-June 2010). Median age of this cohort was 13.9 years (range: 3 days to 17 years), 9/25 (36%) children had known thrombophilic conditions. The locations of VTEs were as follows: extremity, 21/26; portal vein, 2/26; renal vein, 1/26; CNS, 1/27 and 1/26, isolated pulmonary embolism. Using Kuhle's classification 18/26(69%) children were diagnosed to have PTS (mild, 13/18; moderate, 5/18; severe, 0/26)(Table 1). Using EPTSAS, all the children with PTS received a score of >1, thus sensitivity of detecting PTS symptoms was 100%. Among 8 children with “no PTS”, only 6 received “0” score by EPTSAS, thus the specificity of EPTSAS was 75%. Inter-observer agreement was very good (kappa, 0.91) for reporting major symptoms and was fair in reporting symptoms of activity limitation and varicosities (kappa, 0.52 and 0.46 respectively) and was very good (kappa, 0.82) for reporting overall severity of PTS. Among 4 children with non-extremity PTS, 2 (1 renal and 1 portal vein thrombosis) were diagnosed to have “No” PTS and 2 (1, portal vein and 1, sinovenous thrombosis) were diagnosed to have “mild PTS” by Kuhle's classification. Using EPTSAS, 2 of these children (1, renal and 1, portal vein thrombosis) were diagnosed to have “PTS present” and remaining 2 were diagnosed as “PTS likely” implying higher sensitivity of EPTSAS.

The findings of this cohort study suggest that EPTSAS is a valid tool to diagnose the clinical manifestations of PTS in children, specifically non-extremity manifestations. Our scale may need further refinement to improve the inter-observer agreement on the various components of the scale. Our finding needs to be confirmed in a larger cohort of study so that EPTAS can be used for evaluating outcome of children with VTE.

No relevant conflicts of interest to declare.