Reduced Physical Activity Level and Cardiorespiratory Fitness in Children after Acute Venous Thromboembolism

Introduction: Venous thromboembolism (VTE), a disease that includes both deep venous thrombosis (DVT) and pulmonary embolism (PE), has reached epidemic proportions. Accompanying an increase in VTE is the attendant increase in chronic sequelae of VTE, the most frequent of which includes the post-thrombotic syndrome. Given that post-thrombotic sequelae develop despite effective anticoagulation, it is apparent that pharmacology alone is insufficient to eradicate post-VTE disease. Early identification of VTE consequences may offer an opportunity for effective intervention and reduction of long-term morbidity. Currently, no data are available regarding physical activity (PA) post-VTE in children and how that relates to the risk of adverse post-VTE sequelae over time. Therefore, as an important first step, we sought to: (1) to assess self-reported physical activity levels in children 6 month post-VTE and change over time from acute diagnosis, (2) compare activity levels of patients with and without adverse post-VTE sequelae and (3) determine predictors of activity limitations after VTE and assess its association with health related quality of life (HRQoL).

Methods: Data on fifty children were extracted from the ongoing TOP study (clinicaltrials.gov ID NCT03068923) from 2016 to 2017, of which thirty-six were diagnosed with lower extremity DVT and PE. We assessed pre-, 3, and 6 months post VTE physical activity in children between ages 2- 21 years, with an objectively diagnosed lower extremity DVT and PE, using an activity questionnaire (Godin questionnaire). Age, race, ethnicity, gender, BMI, site of VTE, clot burden at diagnosis and follow-up, coagulation activation, dyspnea score, 6-minute walk distance (6MWD) and HRQoL were measured during follow-up.

Results: The median age of subjects was 15.5 years (Range: 2-18). 50% of the participants were males. Twenty subjects had DVT, sixteen had PE and three had both DVT and PE. Of subjects followed for 12 months, only 65% were active at 6 months post diagnosis (defined by Godin questionnaire score ≥ 23) compared to 80% before VTE (mean activity score 138 ± 92 vs. 68 ± 66, p= 0.001). Thirty six % (13/36) of subjects had evidence of post-thrombotic sequelae (a composite of post-thrombotic syndrome (defined by blinded assessment of PTS signs ≥1 and symptoms ≥ 1 using the validated Manco-Johnson Instrument) and post-PE impairment (defined by the presence of dyspnea and reduced 6MWD when compared to age-matched controls) at 12 months post diagnosis). In multivariate analysis, age, race, ethnicity, gender, BMI, site of VTE, baseline or residual clot burden and type of anticoagulant did not predict activity limitations at 6 months post-VTE. Decreased activity level at 6 months post-VTE was not associated with a decreased HRQoL at this time. Insufficient activity, compared with high activity, reduced 6MWD at 6 months post-diagnosis and coagulation activation (defined by D-dimer > 500 ng/mL) at 3 months post-diagnosis, predicted a short-term risk of post-thrombotic sequeale when assessed at 12 months post-diagnosis (odds ratio (OR), 1.55; 95 % CI 1.25 to 1.93; p= <0.001, OR 2.7; 95% CI 1.8 to 13.33; p=0.02 and OR 4.2; 95% CI 1.32 to 12.33; p= 0.02 respectively).

Conclusions: In this ongoing study, 35% of children with DVT and PE had activity limitations post-VTE that adversely influenced short-term post-VTE sequelae. Only 65% of children had resumed their usual activity within 6 months after VTE, highlighting this as a critical time period for interventions aimed at preventing post-VTE disease. Data accrual from the ongoing, prospective study may offer further insight to predict risk factors for decreased PA levels and walking distance in children after VTE.