Real-world monitoring of direct oral anticoagulants in clinic and hospitalization settings

Abstract

Background:The monitoring of the effects of direct oral anticoagulants may be beneficial during emergencies and adverse events. We aimed to explore direct oral anticoagulant monitoring in “real-world” settings, in which monitoring methods are limited and loading time can be estimated based on only patient reports.Methods:In 164 patients, plasma anti-Xa activity was assessed using a STA®-Liquid Anti-Xa reagent (Diagnostica Stago, Asnieres, France), and prothrombin time was measured using HemosIL® RecombiPlasTin 2G (Instrumentation Laboratory, Bedford, MA, USA). The loading time was calculated according to the previous dosing time reported by the patient. In the clinic setting, rivaroxaban and apixaban were administered to 103 patients with atrial fibrillation and a blood sample was tested once during a clinic visit. In the hospitalization setting, edoxaban was administered to 61 patients undergoing arthroplasty for prophylaxis of a venous thrombosis and blood samples were tested 3 and 18 h after the last intake.Results:Plasma Xa activity in the clinical setting ranged widely (rivaroxaban: 1.1–424.4 ng/mL, apixaban: 15.4–469.2 ng/mL) during the 11.7 ± 7.0 h following the previous dose. The values varied over a wide range (up to a factor of 2) at the same loading time, especially around the peak period. The plasma anti-Xa activity of rivaroxaban and apixaban showed linear correlations with prothrombin time (R2 = 0.828 and 0.717, respectively). Edoxaban administration prolonged the prothrombin time by only 1.6 ± 1.1 s from the trough to the peak, to a degree that was negatively correlated with age, but not with plasma creatinine level, creatinine clearance, or body mass index.Conclusion:In real-world settings, plasma anti-Xa monitoring should be interpreted considering the wide variations in data, reflecting the variability in patient-reported loading time and interpatient variability.

Apixaban and rivaroxaban anti-Xa level utilization and associated bleeding events within an academic health system

“…Some researchers have attempted to establish “on therapy” anti-Xa level ranges for apixaban and rivaroxaban in a pragmatic setting [ 11 ], whereas other pharmacokinetic studies conducted in healthy volunteers suggest expected plasma levels based on FXaI type, dose, and time since last dose [ 12 , 13 ]. Certain clinical scenarios such as breakthrough thrombosis, bleeding events, and hepatic and renal insufficiency may warrant assessment of physiologically relevant FXaI concentrations [ [14] , [15] , [16] , [17] , [18] ], and there is some evidence correlating plasma concentrations of certain direct oral anticoagulants (DOAC) such as dabigatran and edoxaban with bleeding events [ 19 , 20 ]. However, there is a paucity of data describing the relationship between FXaI anti-Xa levels and clinical outcomes in patients taking apixaban and rivaroxaban in a real-world setting.…”

Specific Antidotes for Direct Oral Anticoagulants in Life-Threatening Bleeding

“…Однако надежного метода количественного определения антикоагулянтного эффекта ПОАК среди общепринятых коагуляционных тестов нет; применение имеющихся тестов дает только приблизительные сведения, многие тесты не стандартизованы. Реагенты диагностических наборов имеют вариативную чувствительность, трактовка получаемых данных не может считаться однозначной, и носит ориентировочный ха- [16] Xa тест с калибратором [16] тором, время образования разведенное тромбиновое время, белого тромба. HEMOCLOT, анти-экариновый тест фактор Xa тест с калибратором ПВ -протромбиновое время, АЧТВ -активированное частичное тромбопластиновое время, ТВ -тромбиновое время, ТЭГ -тромбоэластограмма, ЭТ -экариновый тест, HEMOCLOT -разбавленное тромбиновое время Лечение антидотами ПОАК должно проводиться подготовленным в вопросах антикоагулянтной терапии специалистом, с лабораторной поддержкой, поскольку неадекватное применение препарата может привести к развитию новых осложнений в виде артериальной и венозной тромбоэмболии, ишемии, кардиальных осложнений.…”

“…По сравнению с АВК ПОАК значительно быстрее достигают эффекта после первичного назначения, с более предсказуемой фармакокинетикой, меньшей вариабельностью в соотношении доза-эффект, они характеризуются более широким терапевтическим окном. ПОАК не подвержены влиянию лекарственных взаимодействий и диеты [16], за исключением дабигатрана. Из представленных в табл.…”

Probable pulmonary embolism with repeat administration of prothrombin complex concentrate in a factor Xa inhibitor patient

“…Knowing whether or not to make a reversal attempt or repeat attempt is also complicated by the lack of availability and reliability of anti‐Xa testing. Several articles have discussed the limitations of anti‐Xa testing including but not limited to inconsistency with results between different agents as well as interpatient variability with regard to the impact of anticoagulant effect . PCC remains a treatment option in this population; however, limited data regarding repeated dosing of PCC for this coagulopathy are available.…”

“…Several articles have discussed the limitations of anti-Xa testing including but not limited to inconsistency with results between different agents as well as interpatient variability with regard to the impact of anticoagulant effect. 14,15 PCC remains a treatment option in this population; however, limited data regarding repeated dosing of PCC for this coagulopathy are available. This case adds to the available information regarding repeat PCC dosing as well as its use in the DOAC population.…”