RESUMEN
INTRODUCTION: Rotational Thromboelastometry (ROTEM) is a point of care method used to monitor coagulation during surgery and to guide transfusion strategies in patients presenting with severe bleeding. The aim of our study was to determine the impact of four direct oral anticoagulants (DOACs) on 3 commonly used ROTEM tests. METHODS: Whole blood samples from 20 healthy donors were spiked in vitro with apixaban, edoxaban, rivaroxaban or dabigatran at 5 different plasma concentrations (0-1000 ng/mL). EXTEM, INTEM and FIBTEM tests were systematically performed. RESULTS: There was a linear relationship between the increase in clotting time (CT) and plasma DOAC concentrations in both the EXTEM and INTEM tests. We found that the DOAC concentration required to double EXTEM CT was 1042 ± 225 ng/mL for apixaban, 134 ± 38 ng/mL for edoxaban, 176 ± 26 ng/mL for rivaroxaban and 284 ± 73 ng/mL for dabigatran. INTEM CT was less sensitive than EXTEM CT whatever the anticoagulant. EXTEM CT was above the normal range for 5 of 5 spiked samples when the plasma concentrations were ~1000 ng/mL for apixaban, ~100 ng/mL for edoxaban, ~200 ng/mL for rivaroxaban and ~200 ng/mL for dabigatran. Maximum Clot Firmness in EXTEM, INTEM and FIBTEM tests was not affected whatever the DOAC or its concentration. CONCLUSION: This study found a DOAC dose-dependent increase in ROTEM CTs. ROTEM tests were only poorly impacted by low levels of edoxaban, rivaroxaban or dabigatran. Apixaban had only a low effect even at high concentrations.
Asunto(s)
Anticoagulantes/administración & dosificación , Anticoagulantes/farmacocinética , Tromboelastografía/instrumentación , Tromboelastografía/métodos , Administración Oral , Adulto , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
INTRODUCTION: Donor-specific alloantibodies (DSAs) cause kidney-allograft loss in chronic antibody-mediated rejection (CAMR). Treatment relies on blocking antibody-producing cells and removing DSAs by apheresis: e.g., double-filtration plasmapheresis (DFPP). MATERIALS AND METHODS: To determine the impact of DFPP (6 or 8 sessions/patient) on clotting factors and natural anticoagulants, and on thrombin generation, we performed a prospective and observational study in five CAMR kidney-transplant patients who received DFPP plus rituximab therapy. Thrombin generation was performed in poor platelet plasma (PPP) with 5 pM tissue factor without and with 2â¯nM recombinant human thrombomodulin. RESULTS: After the first DFPP session, median levels of high molecular-weight proteins (fibrinogen, FV, FVIII, FXI, FXIII, von Willebrand factors and α2-MG) decreased significantly to <50% of baseline values, whereas levels of low molecular-weight factors (<100â¯kDa) were not significantly modified, except for protein S and TFPI. Of note, binding-protein (BP) S, i.e., C4BP, was significantly decreased. Over the course of successive DFPP sessions, both high and lower molecular-weight proteins (<100â¯kDa) with longer half-lives (>2â¯days, prothrombin and factor XII) were significantly decreased. DFPP also highly affected thrombin generation in the absence of thrombomodulin but not significantly in the presence of thrombomodulin. After the first DFPP session, mean endogenous thrombin potential (ETP) and peak thrombin (PH) significantly decreased when the thrombin generation assay was performed without thrombomodulin (respectively, 1084â¯nM·min for ETP and 210â¯nM for PH after the first DFPP session compared to 1616â¯nM·min and 264â¯nM at baseline). In the presence of thrombomodulin, there was only a slight decrease in ETP and PH (respectively 748â¯nM·min, and 172â¯nM after the first DFPP session compared to 822â¯nM·min and 179â¯nM at baseline). After the last session, median ETP and PH decreased respectively to 646â¯nM·min and 143â¯nM without thrombomodulin, and, to 490â¯nM·min and 117â¯nM with thrombomodulin. CONCLUSIONS: DFPP significantly removed high molecular-weight proteins from the haemostatic system and profoundly decreased levels of protein S and TFPI. Overall thrombin-generation balance was only moderately affected in the presence of thrombomodulin. Nevertheless, high depletion of fibrinogen, FXIII and Von Willebrand Factor may expose patients to an increased risk of bleeding.