title: Monitoring hypercoagulability and hypofibrinolysis following acute venous Thromboembolism in children: application of the CloFAL assay in a prospective inception cohort study.
abstract: Although individual thrombophilia tests are frequently performed in children with venous thromboembolism (VTE), global assays provide the opportunity to fill the gap in knowledge regarding their net impact on overall coagulative (and in some cases fibrinolytic) function. We first evaluated analytic sensitivity of the Clot Formation and Lysis (CloFAL) global assay to hypercoagulability and alterations in fibrinolysis, and then characterized changes in plasma coagulative and fibrinolytic capacities over time in children with acute VTE. In plasma ex vivo and in vitro experiments, the CloFAL assay area-under-the-curve (AUC) was analytically sensitive to hypercoagulable states, and its modified fibrinolytic index (FI2) was sensitive to both hyper- and hypofibrinolytic conditions. Clinical data and plasma samples for assay were collected during follow-up of 50 children enrolled in a prospective inception cohort study of VTE from May 2006 to June 2010. Follow-up periods were designated as follows: acute (<1 month post-event), sub-acute (1-3 months), early chronic (3-12 months), and late chronic (>12 months). Since most children were sampled at fewer than three pre-defined follow-up periods, study population findings were grouped by timepoint. AUC was significantly increased, and FI(2) significantly decreased, in the acute period of VTE when compared to healthy controls, indicating hypercoagulability and hypofibrinolysis, respectively. One-third of patients were hypercoagulable, and 23% were hypofibrinolytic, in the late chronic phase. AUC and FI(2) were strongly correlated with functional fibrinogen levels. These findings indicate the utility of the CloFAL assay in monitoring plasma coagulative and fibrinolytic capacities in children with VTE. Studies of its potential role in outcome prediction are ongoing.
authors.affiliation: Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO 80045, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Bombardier
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Villalobos-Menuey
authors.forename: Katherine
authors.initials: K
authors.lastname: Ruegg
authors.forename: William E
authors.initials: WE
authors.lastname: Hathaway
authors.forename: Marilyn J
authors.initials: MJ
authors.lastname: Manco-Johnson
authors.forename: Neil A
authors.initials: NA
authors.lastname: Goldenberg
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D063285:Fibrin Clot Lysis Time / Q000379:methods*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011446:Prospective Studies; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D019851:Thrombophilia / Q000097:blood* / Q000175:diagnosis*; D054556:Venous Thromboembolism / Q000097:blood* / Q000175:diagnosis*