TY - JOUR
T1 - Monitoring hypercoagulability and hypofibrinolysis following acute venous Thromboembolism in Children
T2 - Application of the CloFAL assay in a prospective inception cohort study
AU - Bombardier, Christopher
AU - Villalobos-Menuey, Elizabeth
AU - Ruegg, Katherine
AU - Hathaway, William E.
AU - Manco-Johnson, Marilyn J.
AU - Goldenberg, Neil A.
PY - 2012/9/1
Y1 - 2012/9/1
N2 - 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 FI2 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 FI2 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.
AB - 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 FI2 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 FI2 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.
KW - Coagulation
KW - Fibrinolysis
KW - Global assay
KW - Pediatric
KW - Thromboembolism
UR - http://www.scopus.com/inward/record.url?scp=84865268562&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84865268562&partnerID=8YFLogxK
U2 - 10.1016/j.thromres.2012.03.030
DO - 10.1016/j.thromres.2012.03.030
M3 - Article
C2 - 22551977
AN - SCOPUS:84865268562
VL - 130
SP - 343
EP - 349
JO - Thrombosis Research
JF - Thrombosis Research
SN - 0049-3848
IS - 3
ER -