Markers of coagulation activation, inflammation and fibrinolysis as predictors of poor outcomes after pediatric venous thromboembolism: A systematic review and meta-analysis

Abstract Background Sequelae of venous thromboembolism (VTE) in children include recurrence, development of post thrombotic syndrome (PTS) when venous return from a limb is affected and chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary embolism. Identification of laboratory-based risk factors may be useful for individualized risk assessment for VTE sequelae. Coagulation activation and inflammation may contribute to their pathophysiology. We performed a systematic review to investigate the association between biomarkers of coagulation activation, inflammation and fibrinolysis and adverse VTE outcomes in children and young adults. Methods A systematic search of electronic databases, PubMed (NIH), EMBASE (Ovid), Web of Science (Thompson Reuters), and SCOPUS (Elsevier) for studies published through November 2016 was conducted using “VTE” including MeSH terms for “coagulation activation,” “inflammation” and “fibrinolysis,” with no limit on publication date. A study was eligible for inclusion when it evaluated patients ( Results Our search strategy yielded 200 references. A total of 3 cohort studies representing 220 patients with VTE were included. Two authors independently assessed all references for inclusion. Three studies (2 prospective cohort and one mixed cohort study) were identified that reported on biomarkers of coagulation activation, inflammation and fibrinolysis, checked at least once after VTE diagnosis and assessed association with primary outcomes of recurrent VTE, PTS and CTEPH. Studies varied with regards to definition of outcomes, the type of biomarkers measured and time point of measurement. We were unable to meta-analyze results due to marked clinical heterogeneity and Conclusions Elevated D-dimer, FVIII and lupus anticoagulant show promise for predicting recurrent VTE and PTS in children and young adults. Further research is needed to elucidate whether these markers might be useful to predict development of adverse outcomes after VTE in children.