Fibrinography and thrombography (thrombodynamics-4D) in atrial fibrillation assessment of direct oral anticoagulants in geriatrics patients aged 80 years and older receiving direct oral anticoagulant therapy

Figures

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  Figure 1. Fibrinography parameters (Thrombodynamics-4D) as a function of direct oral anticoagulant (DOAC) concentrations in spiking experiments. (A) Lag time (Tlag), (B) initial rate of clot growth (Vi), (C) rate of clot growth (V), (D) clot size (CS) at 30 minutes, (E) clot density (D), and (F) time to spontaneous clotting (Tsp). Pooled normal plasma (Cryocheck) samples were spiked with rivaroxaban (R), apixaban (A), or dabigatran (D) to obtain final concentrations ranging from 0 to 1000 nM. DOAC concentrations were measured in the spiked samples. Concentrations are expressed in both nanograms per milliliter (ng/mL) and nanomolar (nM) to facilitate comparisons between R (red dots), A (blue dots), and D (green dots). Spontaneous clotting occurred in n = 5 (14%), n = 5 (14%), and n = 12 (33%) samples spiked with R, A, and D, respectively, mainly at low DOAC concentrations.

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  Figure 2. Thrombography parameters (Thrombodynamics) as a function of direct oral anticoagulant (DOAC) concentrations in spiking experiments. (A) Lag time (Lag_ATG), (B) time to peak (Tmax_ATG), (C) maximal thrombin concentration (peak height, Cmax_ATG), (D) endogenous thrombin potential (ETP_ATG), (E) stationary amplitude of thrombin moving peak (Ast), and (F) rate of thrombin peak propagation (Vt). Pooled normal plasma (Cryocheck) samples were spiked with rivaroxaban (R), apixaban (A), or dabigatran (D; see Figure 1 legend). Concentrations of DOACs are expressed in both nanograms per milliliter (ng/mL) and nanomolar (nM) to facilitate comparisons between R (red dots), A (blue dots), and D (green dots). ETP, endogenous thrombin potential.

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  Figure 3. Fibrinography parameters (Thrombodynamics) as a function of direct oral anticoagulant (DOAC) concentrations in all Assessment of Direct oral Anticoagulants in Geriatrics (ADAGE) patients. (A) Lag time (Tlag), (B) initial rate of clot growth (V), (C) clot size (CS) at 30 minutes, (D) clot density (D), and (E) time to spontaneous clotting (Tsp). Concentrations of DOACs are expressed in both nanograms per milliliter (ng/mL) and nanomolar (nM) to facilitate comparisons between rivaroxaban (R; red dots), apixaban (A; blue dots), and dabigatran (D; green dots). Dashed lines indicate the locally determined reference intervals in healthy subjects. Of note, 1 patient on R (676 ng/mL) is represented by an open black diamond (beyond the limits of quantification). a.u., arbitrary units.

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  Figure 4. Thrombography parameters (Thrombodynamics-4D) as a function of direct oral anticoagulant (DOAC) concentrations in all Assessment of Direct oral Anticoagulants in Geriatrics (ADAGE) patients. (A) Lag time (Lag_ATG), (B) time to peak (Tmax_ATG), (C) maximal thrombin concentration (Cmax_ATG), (D) endogenous thrombin potential (ETP_ATG), and (E) stationary amplitude of thrombin moving peak (Ast). Concentrations of DOACs are expressed in both nanograms per milliliter (ng/mL) and nanomolar (nM) to facilitate comparisons between rivaroxaban (R; red dots), apixaban (A; blue dots), and dabigatran (D; green dots). Dashed lines indicate the locally determined reference intervals in healthy subjects. Of note, 1 patient on R (676 ng/mL) is represented by an open black diamond (beyond the limits of quantification). AU, arbitrary units; ETP, endogenous thrombin potential.

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  Figure 5. Fibrinography parameters (Thrombodynamics-4D) in a subset of Assessment of Direct oral Anticoagulants in Geriatrics (ADAGE) patients on rivaroxaban, apixaban, or dabigatran (reduced dose) at peak time (Tmax) and trough (Tmin) compared with pooled normal plasma (Normal Pool; gray) and elderly direct oral anticoagulant (DOAC)-free subjects (Elderly control; yellow). (A) Lag time (Tlag), (B) initial rate of clot growth (Vi), (C) clot size (CS) at 30 minutes, and (D) time of spontaneous clotting (Tsp). Fibrinography parameters are presented as scattered dot plots. ADAGE patients on rivaroxaban o.d. 15 mg (pink) or 20 mg (red); ADAGE patients on apixaban twice daily (b.i.d.) 2.5 mg (light blue) or 5.0 mg (dark blue); ADAGE patients on 110 mg dabigatran twice daily (green). Dashed lines indicate the locally determined reference intervals in healthy subjects. Comparisons between the mean values of each parameter in the Elderly control group and ADAGE patients are shown as ∗∗∗P < 10-3, ∗∗P < 10-2, ∗P < .05 (Mann–Whitney U-test). Of note, 1 patient on rivaroxaban (676 ng/mL) is represented by an open black diamond (beyond the limits of quantification). b.i.d., twice-daily; o.d., once daily.

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  Figure 6. Thrombography parameters in a subset of Assessment of Direct oral Anticoagulants in Geriatrics (ADAGE) patients on rivaroxaban, apixaban, or dabigatran (reduced dose) at peak time (Tmax) and time to trough (Tmin) compared with pooled normal plasma (Normal Pool; gray) and direct oral anticoagulant (DOAC)-free elderly subjects (Elderly control; yellow). (A) Lag time (Lag_ATG), (B) time to peak (Tmax_ATG), (C) maximal thrombin concentration (Cmax_ATG), (D) endogenous thrombin potential (ETP_ATG), and (E) stationary amplitude of thrombin moving peak (Ast). Thrombography parameters are presented as scattered dot plots. ADAGE patients on rivaroxaban o.d. 15 mg (pink) or 20 mg (red); ADAGE patients on apixaban 2.5 mg (light blue) or 5.0 mg (dark blue) twice daily; ADAGE patients on 110 mg dabigatran (green) twice daily. Dashed lines indicate the locally determined reference intervals in healthy subjects. Comparisons between the mean values of each parameter in the elderly control group and ADAGE patients are shown as ∗∗∗P < 10-3, ∗∗P < 10-2, ∗P < .05 (Mann–Whitney U-test). Of note, 1 patient on rivaroxaban (676 ng/mL) is represented by an open black diamond (beyond the limits of…