[Interference of oral anti-Xa anticoagulants during monitoring of unfractionated heparin treatments: practical and future attitudes]. / Interférence des anticoagulants oraux directs anti-Xa lors de la surveillance des traitements par héparine non-fractionnée : attitudes pratiques et à venir.

Contrary to direct oral anticoagulants (DOAC), unfractionated heparin (UFH) requires daily monitoring when administered at therapeutic dose. At present, UFH monitoring is preferably carried out by measuring plasma anti-Xa activity, however, in patients previously treated with an anti-Xa DOAC and switched to UFH, there is a high risk of DOAC interfering with the measurement of UFH anti-Xa activity. Residual anti-Xa DOAC in the sample can lead to an overestimation of the anticoagulant activity attributed to heparin and thus to incorrect anticoagulation. This risk of interference should not be overlooked because interference may occur even at concentration of DOAC below the hemostatic safety threshold and can last several days. To overcome this issue, several alternatives are being studied. This note provides an update on anti-Xa DOAC interference and different strategies available in current practice. It also underlines the importance of communication between biologists and clinicians on anticoagulant treatments received by patients.

Tinzaparin, an alternative to subcutaneous unfractionated heparin, in patients with severe and end-stage renal impairment: a retrospective observational single-center study.

BACKGROUND: Tinzaparin could be easier to manage than unfractionated heparin, in patients with severe renal impairment. However, clinical and pharmacological data regarding its use in such patients are lacking. The aims of this study were to determine, in patients with eGFR<30 mL.min-1: tinzaparin pharmacokinetics (PK) parameters, using a population PK approach and bleeding and thrombotic complications. METHODS: We performed a retrospective observational single-center study, including in-patients with eGFR< 30 mL.min-1, receiving prophylactic (4500 IU.day-1) or therapeutic (175 IU.kg-1.day-1) tinzaparin. Measured anti-Xa levels were analyzed using a non-linear mixed effects modelling approach. Individual predicted tinzaparin exposure markers at steady state were calculated for each patient and dosing regimen. The PK was also evaluated through Monte-Carlo simulations, based on the final covariate model parameter estimates. RESULTS: Over a 22-month period, 802 tinzaparin treatment periods in 623 patients were analysed: two-thirds received a prophylactic dose, 66% had an eGFR<20 mL.min-1, and 25% were on renal replacement therapy. In patients for whom anti-Xa measurements were performed (n=199, 746 values), PK parameters, profiles and Cmax were comparable to those in patients without renal impairment or in healthy volunteers. In the whole population, major bleeding occurred in 2.4% and 3.5% of patients receiving prophylactic and therapeutic doses, over a median 9- and 7-days treatment period, respectively. No patients had thrombotic complication. CONCLUSION: Tinzaparin PK parameters and profiles were not affected by renal impairment. This suggests that tinzaparin, at therapeutic or prophylactic dose, could be an alternative to unfractionated heparin in hospitalized patients with severe renal impairment.