In Children with Provoked Venous Thromboembolism, Increasing Plasma Coagulability during the First 3 Months Postdiagnosis is Prognostic of RecurrenceFunding This study was funded by the following grants: All Children's Hospital Foundation Grant; U.S. Department of Health and Human Services; National Institutes of Health’s National Lung and Blood Disorders Institute (grant no. 1 U01 HL130048).
11 October 2019
22 February 2020
05 May 2020 (online)
Prognostic factors for venous thromboembolism (VTE) recurrence following provoked VTE are largely unknown. Using the Clot Formation and Lysis (CloFAL) assay, single institutional research has shown overall improvement in acute hypercoagulability during the first 3 months postpediatric VTE, yet a rise in plasma coagulability in a subgroup of patients. We sought to define the incidence of rise in coagulability during the first 3 months post-provoked VTE, to investigate its relationship with elevated D-dimer, and to test the hypothesis that a marked rise in coagulability is independently prognostic of VTE recurrence. CloFAL and D-dimer assays were performed on plasma at 4 to 6 weeks and 3 months post-VTE in the Johns Hopkins pediatric VTE cohort and National Institutes of Health-sponsored Kids-DOTT trial. Associations of VTE recurrence with D-dimer and CloFAL assay measures were evaluated via logistic regression. Eighty-seven patients were included. Median follow-up was 1 year. Complete veno-occlusion was determined in 12% at 6 weeks. During the first 3 months post-VTE, a marked rise in coagulability was observed by CloFAL assay in 17% of patients, while D-dimer was elevated in 21%. Recurrent VTE occurred in 10% of patients. CloFAL assay, but not D-dimer, was associated with recurrence (odds ratio [OR] 5.87, 95% confidence interval [95% CI], 1.34–25.8]). After adjustment for veno-occlusion, patients with a marked rise in coagulability by CloFAL assay had a 10-fold increased risk of recurrent VTE (OR 10.33 [95% CI, 1.83–58.19]). Future work should seek to elucidate the mechanisms underlying a rise in plasma coagulability following provoked VTE and to substantiate its prognostic utility for recurrent VTE.
This work was presented at the oral abstract sessions of the 59th American Society of Hematology Annual Meeting, 2017, Atlanta, GA, United States.
N.A.G. designed the study; M.B. and N.A.G. performed patient enrollment and data collection; M.G.M. performed the CloFAL assay; E.K.A. performed data analysis; M.B. and N.A.G. performed the interpretation of findings; M.B. and N.A.G. drafted manuscript; and all authors provided critical revisions and approved the manuscript.
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