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Supplemental Table 1. Statistical analysis of data presented in Table 1 (main manuscript). Data were analyzed by repeated measures ANOVA with Greenhouse- Geisser correction for the sphericity assumption on variances, followed by the comparison of all parameters (R, Angle, TMRTG, and MRTG) at each experimental condition with the baseline (No Drug). Benjamini-Hochberg method was used to adjust p-value in multiple comparisons to avoid type I error inflation. P-values are presented,

*p<0.05 vs. No Drug (for Dabigatran groups); #P < 0.05 (for Dabigatran + Idarucizumab groups); and #P < 0.05 (for Chandler loop experiments).

In-vitro A

Dab (ng/ml) P-value (R) P-value (Angle) P-value (MRTG) P-value (TMRTG) Overall <0.0001* <0.0001* <0.0001* <0.0001*

Dab 18.75 0.846 0.852 0.383 0.885

Dab 37.5 0.813 0.901 0.558 0.885

Dab 75 0.755 0.852 0.296 0.885

Dab 150 0.480 0.901 0.383 0.534

Dab 300 0.114 0.006* 0.850 0.022*

Dab 600 <0.003* <0.0001* <0.0001* <0.0001*

Dab 1200 <0.0001* <0.0001* <0.0001* <0.0001*

Dab 2400 <0.0001* <0.0001* <0.0001* <0.0001*

In-vitro B

Dab (ng/ml) + Ida(µg/ml)

P-value (for R)

P-value (Angle)

P-value (MRTG)

P-value (TMRTG) Overall <0.0001# <0.0001# 0.002# <0.0001#

Dab 18.75+IDA 125 0.989 0.799 0.634 0.516

Dab 37.5+IDA 125 0.989 0.799 0.634 0.516

Dab 75+IDA 125 0.989 0.799 0.916 0.516

Dab 150+IDA 125 0.989 0.799 0.310 0.516

Dab 300+IDA 125 0.989 0.799 0.634 0.516

Dab 600+IDA 125 0.989 0.799 0.916 0.516

Dab 1200+IDA 125 0.989 0.799 0.310 0.516

Dab 2400+IDA 125 <0.0001# <0.0001# 0.02# <0.0001#

Dab 2400+IDA 250 0.725 0.838 0.410 0.516

Dab 2400+IDA 500 0.989 0.799 0.620 0.516

Chandler loop C

Drug (ng/ml) P-value (for R)

Overall <0.0001#

Dab 2400 <0.0001#

Dab 4800 <0.0001#

Dab 9600 <0.0001#

Dab 19200 <0.0001#

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Supplemental Table 2. Parameters measure during 120 min in the cardiopulmonary bypass circuit stimulation with Dabigatran 10000ng/ml. Data were analyzed by repeated measures ANOVA with Greenhouse-Geisser correction for the sphericity assumption on variances. Benjamini-Hochberg method was used to adjust p-value in multiple comparisons to avoid type I error inflation. All data are means ± SD, n=6; for R (reaction time) *p<0.05 vs. No Drug.

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Supplemental Table 3. Parameters measure during 120 min in the cardiopulmonary bypass circuit stimulation with Dabigatran 7500ng/ml. Data were analyzed by repeated measures ANOVA with Greenhouse-Geisser correction for the sphericity assumption on variances. Benjamini-Hochberg method was used to adjust p-value in multiple comparisons to avoid type I error inflation. All data are means ± SD, n=6; for R (reaction time) *p<0.05 vs. No Drug.

Dabigatran 7500 ng/ml (with Ca 5mmol/L added) No Drug 1min 30min 60min 120min R min (rapidTEG) 0.4±0.2 47.7±3.9* 50.8±5.9* 48.8±6.0* 45.2±5.3*

pH 7.33±0.17 7.43±0.07 7.5±0.09 7.4±0.07 7.4±0.07

pCO2 mmHg 37.5±6.8 31.2±2.5 30.9±1.5 26.2±1.2 27±1.2

pO2 mmHg 608±17 617±22 589±82 534±28 515±47

BE ecf mmol/L -5.3±9.1 -2.9±4.9 -1.1±5.9 -1.0±4.2 -1.6±4.2

Hct % 30.7±2.7 28.6±2.5 29.3±2.9 29.2±2.7 29.5±2.9

Ca2+ mmol/L - 5.1±0.9 4.2±0.7 5.6±2.7 5.5±2.5

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bypass circuit stimulation with Dabigatran 5000ng/ml. Data were analyzed by repeated measures ANOVA with Greenhouse-Geisser correction for the sphericity assumption on variances. Benjamini-Hochberg method was used to adjust p-value in multiple comparisons to avoid type I error inflation. All data are means ± SD, n=6; for R (reaction time) *p<0.05 vs. No Drug.

Dabigatran 5000 ng/ml (with Ca 5mmol/L added) No Drug 1min 30min 60min 120min R min (rapidTEG) 0.4±0.2 34.5±4.2* 37.4±6.9* 33.8±5.9* 40.0±27.5*

pH 7.55±0.12 7.43±0.05 7.50±0.05 7.40±0.05 7.40±0.07

pCO2 mmHg 30.7±3.9 31.8±2.2 31.7±2.2 31.9±1.2 32.5±3.7

pO2 mmHg 494±114.2 590±46 572±64 580±77 629±64

BE ecf mmol/L -4.2±8.3 -3.1±3.7 -1.4±2.7 -2.2±2.9 -3.6±2.7

Hct % 30.0±2.5 28.8±2.7 28.6±2.5 28.8±2.2 29.2±2.2

Ca2+ mmol/L - 5.4±0.5 4.5±0.2 3.9±1.2 3.9±1.2

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Supplemental Table 5. Parameters measure during 120 min in the cardiopulmonary bypass circuit stimulation with Heparin 3U/ml. Data were analyzed by repeated

measures ANOVA with Greenhouse-Geisser correction for the sphericity assumption on variances. Benjamini-Hochberg method was used to adjust p-value in multiple

comparisons to avoid type I error inflation. All data are means ± SD, n=6; for R (reaction time) *p<0.05 vs. No Drug.

Heparin 3 U/mL (with Ca 5mmol/L added) No Drug 1min 30min 60min 120min R min (rapidTEG) 0.41±0.05 6.38±3.6* 4.56±1.0* 4.74±1.74* 3.66±1.34*

pH 7.35±0.17 7.42±0.12 7.46±0.1 7.45±0.07 7.45±0.07

pCO2 mmHg 38.8±8.9 35.0±4.9 33.4±3.1 31.7±1.1 31.8±2.7

pO2 mmHg 519±212 545±205 534±199 480±237 561±207

BE ecf mmol/L -3.8±9.7 -1.5±6.6 -0.9±4.1 -1.7±4.4 -1.7±1.8

Hct % 30.5±2.9 28.7±2.3 28.7±2.3 29±2.3 29±2.3

Ca2+ mmol/L - 6.8±4.1 5.4±1.9 5.1±1.5 4.9±1.1

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