Assessing the anticoagulant effect of dabigatran in children: An in vitro study. Issue 4 (April 2015)

• Record Type: Journal Article
• Authors: Dietrich, Kevin; Stang, Linda; van Ryn, Joanne; Mitchell, Lesley G.
• Is Part Of: Thrombosis research. Volume 135:Issue 4(2015)
• Page Start: 630
• Page End: 635
• Publication Date: 2015-04
• Subjects: Thrombosis -- Periodicals; 616.135
• DOI: 10.1016/j.thromres.2015.01.017
• Languages: English
• ISSNs: 0049-3848

Abstract

<abstract abstract-type="author" id="ab0005"> <title id="st0005">Abstract</title> <sec> <title id="st0010">Objectives</title> <p id="sp0005">Age-related changes in the hemostatic system result in variation in response to anticoagulants and coagulation assays over childhood. This study used <italic>in vitro</italic> methods to determine i) optimum coagulation assays for dabigatran in children and ii) anticoagulant effect of dabigatran across pediatric age groups.</p> </sec> <sec> <title id="st0015">Materials and Methods</title> <p id="sp0010">Pooled plasma samples from healthy children aged 0 to < 1, 1 to < 5, 5 to < 10, 10 to < 17 years and adults were spiked with increasing concentrations of dabigatran and the effect was assessed in five coagulation assays. The samples were also assessed for overall hemostasis potential using a fibrin clot formation and lysis assay.</p> </sec> <sec> <title id="st0020">Results</title> <p id="sp0015">In all five coagulation assays, there were no differences in responses to dabigatran over all pediatric age groups. The international normalized ratio was the least sensitive measure. Activated partial thromboplastin time showed moderate sensitivity and a nonlinear response curve. Thrombin time (TT), dilute TT (dTT) and ecarin clotting time were linearly correlated with dabigatran concentrations; however, the ecarin time and TT were overly sensitive. In the overall hemostasis potential assay, increasing dabigatran concentrations delayed the initiation of clot formation and reduced the time to 50% clot lysis. The responses to initiation of clot formation and clot lysis were consistent across all pediatric groups and comparable to responses in adults.</p> </sec> <sec> <title id="st0025">Conclusion</title> <p id="sp0020">The dTT is the most suitable assay for measuring dabigatran concentrations in children. Fibrin clot generation and lysis assay responses to dabigatran in children over all ages were consistent and comparable to those of adults.</p> </sec> </abstract>