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Thrombin generation and other coagulation parameters in a patient with homozygous congenital protein S deficiency on treatment with rivaroxaban.

Authors :
Tripodi A
Martinelli I
Chantarangkul V
Clerici M
Artoni A
Passamonti S
Peyvandi F
Source :
International journal of hematology [Int J Hematol] 2016 Feb; Vol. 103 (2), pp. 165-72. Date of Electronic Publication: 2015 Nov 19.
Publication Year :
2016

Abstract

Rivaroxaban, which targets factor Xa and does not reduce proteins C/S, was chosen to treat a 6-year-old girl with homozygous protein S (PS) deficiency who developed skin necrosis while on warfarin. Owing to the lack of experience with rivaroxaban in children, the girl was started with 5 mg once-daily, which was gradually increased to 40 mg daily. The increasing dosage was driven by the need to avoid recurrence of skin necrosis. During dose-escalation, four pharmacokinetics assays were carried out measuring drug plasma concentrations and their effect on hemostatic parameters. We report the laboratory work-up, with special reference to parameters of thrombin-generation. Rivaroxaban concentrations by HPLC were correlated with those by the anti-factor Xa assay (r(2) = 0.92, p < 0.01), but there was an overestimation by HPLC. Thrombin-generation parameters, such as the area under the curve (referred to as ETP), peak-thrombin, and velocity-index, when measured after addition of thrombomodulin, showed unexpected changes: ETP decreased, but peak-thrombin and velocity-index increased. Similar patterns were obtained in a PS-depleted plasma and in plasma from patients with heterozygous PS deficiency, but not in plasma from controls. In conclusion, these preliminary results suggest that PS may be a determinant of velocity and peak-thrombin, but not of the total amount of thrombin generated.

Details

Language :
English
ISSN :
1865-3774
Volume :
103
Issue :
2
Database :
MEDLINE
Journal :
International journal of hematology
Publication Type :
Academic Journal
Accession number :
26586461
Full Text :
https://doi.org/10.1007/s12185-015-1898-6