New oral antithrombotics: a need for laboratory monitoring. For

Mismetti, Patrick; Laporte, Silvy

doi:10.1111/j.1538-7836.2010.03764.x

Cited by 80 publications

(63 citation statements)

References 40 publications

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“…[2][3][4][5] It has been surmised, however, that certain patients could benefit from dose adaptation. 22,23 This raises the question of whether dose adaptation should be restricted to certain categories or whether it could improve the results with direct inhibitors so that these become better than the -admittedly not ideal -results of prophylaxis with vitamin K antagonists. This article deals with a partial problem pertaining to this question, viz.…”

Section: Discussionmentioning

confidence: 99%

Large inter-individual variation of the pharmacodynamic effect of anticoagulant drugs on thrombin generation

2012

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Anticoagulation by a standard dosage of an inhibitor of thrombin generation presupposes predictable pharmacokinetics and pharmacodynamics of the anticoagulant. We determined the inter-individual variation of the effect on thrombin generation of a fixed concentration of direct and antithrombin-mediated inhibitors of thrombin and factor Xa. Thrombin generation was determined by calibrated automated thrombinography in platelet-poor plasma from 44 apparently healthy subjects which was spiked with fixed concentrations of otamixaban, melagatran, unfractionated heparin, dermatan sulfate and pentasaccharide. The variability of the inhibitory effect of the different anticoagulants within the population was determined using the coefficient of variation, i.e. the standard deviation expressed as a percentage of the mean. The inter-individual coefficients of variation of the endogenous thrombin potential and peak height before inhibition were 18% and 16%, respectively and became 20%-24% and 24%-43% after inhibition. The average inhibition of endogenous thrombin potential and peak height (ETP, peak) brought about by the anticoagulants was respectively: otamixaban (27%, 83%), melagatran (56%, 63%), unfractionated heparin (43%, 58%), dermatan sulfate (68%, 57%) and pentasaccharide (25%, 67%). This study demonstrates that the addition of a fixed concentration of any type of anticoagulant tested causes an inhibition that is highly variable from one individual to another. In this respect there is no difference between direct inhibitors of thrombin and factor Xa and heparin(-like) inhibitors acting on the same factors. Large inter-individual variation of the pharmacodynamic effect of anticoagulant drugs on thrombin generation

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Section: Discussionmentioning

confidence: 99%

Large inter-individual variation of the pharmacodynamic effect of anticoagulant drugs on thrombin generation

2012

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“…Susceptibility to venous thrombosis (VT) is heterogeneous, involving multiple genetic and environmental risk factors [1].…”

Section: Disclosure Of Conflict Of Interestsmentioning

confidence: 99%

“…10 Arias-Salgado EG, Tao J, Gonzalez-Manchon C, Butta N, Vicente V, Ayuso MS, Parilla R. Nonsense mutation in exon-19 of GPIIb associated with thrombasthenic phenotype. In the debate published in the April issue of this journal, the authors give us a series of important reasons for and against monitoring during treatment with the new oral anticoagulants [1,2].…”

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confidence: 99%

When a virtue becomes a problem. The new oral anticoagulants

Díaz-Cremades

Ruano

Fernández‐Fuertes

2010

Journal of Thrombosis and Haemostasis

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“…Unfractionated heparin (UFH) has been the parenteral anticoagulant of choice for more than 50 years [2][3][4]. Even though new anticoagulant drugs inhibiting thrombin (30%) and factor Xa (FXa) (70%) are under clinical development [5][6][7], UFH continues to be administered for short-term prophylaxis because it is effective, inexpensive, and a protamine sulfate antidote exists to rapidly reverse bleeding [8].…”

Section: Introductionmentioning

confidence: 99%

Quantification of unfractionated heparin in human plasma and whole blood by means of novel fluorogenic anti-FXa assays

Castro-López

Harris

O’Donnell

et al. 2011

Journal of Pharmaceutical and Biomedical Analysis

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t r a c tNovel and sensitive plate-based fluorogenic anti-factor Xa (FXa) assays were investigated to quantify unfractionated heparin (UFH) in human plasma and whole blood within the therapeutic ranges of 0-1.6 U/mL and 0-0.8 U/mL, respectively. Two fluorogenic anti-FXa assay methods were defined for low (0-0.6 U/mL) and high (0.6-1.2 U/mL) pharmacologically relevant UFH concentration ranges in pooled human plasma. In both cases significant differences were observed at intervals of 0.2 U/mL (P < 0.05). The semi-logarithmic plots of the calibration curves in the low and high UFH range were both fitted to linear regressions with correlation coefficients of 0.96 and >0.99, respectively. The assay was also optimized for whole blood which was capable of differentiating UFH concentrations at intervals of 0.2 U/mL (P < 0.05) in the range of 0-0.4 U/mL. The statistically different results were fitted to a linear regression with a correlation coefficient of >0.99. The results obtained in this study could assist diagnostic laboratories towards improved monitoring of UFH therapy.

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New oral antithrombotics: a need for laboratory monitoring. For

Abstract: See also Bounameaux H, Reber G. New oral antithrombotics: a need for laboratory monitoring. Against. This issue, pp 627–30.

Cited by 80 publications

References 40 publications

Large inter-individual variation of the pharmacodynamic effect of anticoagulant drugs on thrombin generation

Large inter-individual variation of the pharmacodynamic effect of anticoagulant drugs on thrombin generation

When a virtue becomes a problem. The new oral anticoagulants

Quantification of unfractionated heparin in human plasma and whole blood by means of novel fluorogenic anti-FXa assays

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