Bleeding prediction by rotational thromboelastometry in chronic hemodialysis patients with non-valvular atrial fibrillation on apixaban

doi:10.4330/wjc.v17.i12.112046

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Dec 26, 2025 (publication date) through Dec 24, 2025

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World Journal of Cardiology

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1949-8462

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Cardiol. Dec 26, 2025; 17(12): 112046
Published online Dec 26, 2025. doi: 10.4330/wjc.v17.i12.112046

Table 1 Characteristics of patients classified into bleeding and no bleeding groups, n (%)

Characteristic clinical and epidemiologic	All patients (N = 19)	No Bleeding (n = 13)	Bleeding (n = 6)	P value
Age (year)	73 ± 12	73 ±12	74 ± 6	0.827
Sex (male = 1/females = 2)	13/6	9/4	4/2	0.911
Dialysis vintage (months)	4.56 ± 3.5	4.83 ± 0.9	4.0 ± 2.4	0.633
Body weight (kg)	83 ± 20	85 ± 20.	79 ± 21	0.513
Diabetes mellitus	7 (36.8)	5 (38.5)	2 (26.8)	0.829
Hypertension	12 (80)	9 (81.8)	3 (75)	0.770
Cardiac artery disease	5 (26.3)	4 (30.8)	1 (5.2)	0.516
Previous bleeding episodes	5 (26.3)	4 (30.8)	1 (5.2)	0.516
Stroke	4 (21.1)	2 (15.4)	2 (33.3)	0.372
Frailty scale	3.8 ± 1.8	3.8 ± 2.0	3.8 ± 1.5	0.944
Charlson Comorbidity Index	5.2 ± 1.3	5.2 ± 1.4	5.2 ± 1.0	0.933
Stroke/bleeding risk assessment (score)
CHA₂DS₂-VASc score	3 (2-5)	3 (2-5)	3 (2-4)	0.532
HAS-BLED score	3 (2-3)	2 (1.5-3)	3.5 (2.7-5.5)	0.070
ATRIA risk score	6 (5-8)	6 (3-7)	5.5 (5-8.5)	0.723
Modified hemodialysis score	1 (0-2)	1 (0-2)	1 (0.75-2)	0.550
Drugs
ACEIs/ARBs	8 (42.1)	7 (53.8)	1(5.2)	0.127
β-blockers	8 (42.1)	6 (46.2)	2 (33.3)	0.599
Antiarrhythmics	5 (26.3)	5 (38.5)	0 (0)	0.077
Statins	10 (52.6)	7 (53.8)	3 (30)	0.876
Acetylasalicylic acid/clopidogel	4 (21.1)	4 (30.8)	0 (0)	0.126

ACEI: Angiotensin-converting enzyme inhibitor; ARB: Angiotensin receptor blocker.

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Table 2 Coagulation parameters and apixaban levels, median (interquartile range)

Conventional coagulation tests (pre/post apixaban)	All patients (N = 19)	No Bleeding (n = 13)	Bleeding (n = 6)	P value
Prothrombin time-pre (second)	11.7 (11.3-12.8)	11.4 (11.1-12.1)	12.7 (11.7-13.8)	0.143
aPTT-pre (second)	34 (31-38)	34 (28-39)	32 (35-37)	0.597
Fibrinogen-pre (mg/dL)	440 (388-512)	440 (383-503)	467 (415-516)	0.394
D-dimers-pre (ng/mL)	633 (355-1423)	416 (307-1496)	713 (618-1504)	0.765
Prothrombin time-post (second)	12 (12-13)	11.5 (12-13)	13 (11.5-14)	0.636
aPTT-post (second)	34 (28-38)	34 (28-39)	35 (30-39)	0.535
Fibrinogen-post(mg/dL)	443 (359-528)	440 (355-518)	489 (340-536)	0.442
D-dimers-post (ng/mL)	585 (375-1418)	491 (217-1494)	699 (576-1404)	0.890
RΟΤΕΜ (pre/post apixaban)
Clotting time-pre (second)	83 (71-95)	85 (71-93)	80 (68-113)	0.372
Clot formation time-pre (second)	57 (51-68)	57 (53-66)	59 (47-82)	0.750
An angle-pre (rad)	78 (75-79)	79 (77-80)	78 (74-81)	0.992
Max clot firmness-pre (mm)	71 (66-73)	69 (66-73)	72 (65-74)	0.693
Maximum clot lysis-pre (%)	7 (6-8)	6 (4-7)	6 (5-7)	0.992
Li60-pre (%)	96 (94-97)	95 (94-97)	97 (93-98)	0.904
Clotting time-post (second)	102 (81-116)	87 (77-107)	118 (100-144)	0.008^a
Clot formation time-post (second)	66 (52-76)	66 (50-76)	68 (54-77)	0.692
An angle-post (rad)	77 (75-77)	77 (75-80)	77 (76-79)	0.961
Max clot firmness-post (mm)	69 (66-73)	69 (67-73)	71 (65-75)	0.865
Maximum clot lysis-post (%)	6 (4-7)	7 (6-10)	7 (5-10)	0.975
Li60-post (%)	95 (93-97)	94 (93-97)	96 (93-98)	0.719
CTdiff	8 (2-28)	7 (1.5-19)	38 (3-52)	0.013
PFA-200 (epinephrine)
Closure time (second)	135 (106-214)	123 (113-187)	172 (99-272)	0.425
Apixaban levels
Apixaban-trough (ng/mL)	93 (26-166)	93 (53-151)	65 (0-214)	0.918
Apixaban-peak (ng/mL)	163 (107-234)	183 (103-230)	139 (86-331)	0.841
Apxdiff	53 (27-107)	53 (35-100)	76 (21-137)	0.555

^aP < 0.01.

aPTT: Active partial thromboplastin time; ROTEM: Rotational thromboelastometry; Li60: Lysis index 60 minutes after clotting time; CTdiff: Difference between EXTEM clotting time after and prior administration of apixaban; PFA-200: Platelet Function Analyzer-200; Apxdiff: Difference between peak and trough levels of apixaban.

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Table 3 Correlations of EXTEM clotting time with apixaban levels and Platelet Function Analyzer-200 assay

	Apx-trough	Apx-peak	Apxdiff	CT-pre	CT-post	CTdiff	PFA-200
Apx-trough	1	0.882^b		770^c
Apx-peak	0.882^c	1		0.767^c	0.526^a
Apxdiff			1			0.464^a
CT-pre¹	0.770^c	0.767^c		1	0.616^b
CT-post²		0.526^a		0.616^b	1	0.645^b
CT-diff			0.464^a		0.645^b	1	0.565^a
PFA-200						0.565^a	1

^aP < 0.05.

^bP < 0.01.

^cP < 0.001.

¹Prior administration of apixaban.

²After administration of apixaban.

Apx: Apixaban; Apxdiff: Difference between peak and trough levels of apixaban; CT: Clotting time; CTdiff: Difference between EXTEM clotting time after and prior administration of apixaban; PFA-200: Platelet Function Analyzer-200.

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Table 4 Factors related to rotational thromboelastometry with EXTEM reagent clotting time-post

Parameter	β	SD	Standard β	P value	R change
Constant	46.57	16.34
Apixaban-peak	0.18	0.05	0.66	0.004	0.23
PFA-200 (closure time)	0.14	0.06	0.44	0.038	0.38

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Table 5 Multiple logistic regression analysis to identify bleeding risk factors in 19 hemodialysis patients

Parameter	Univariate		Multivariable
Parameter	OR (95%CI)	P value	OR (95%CI)	P value
CT-post (up 1 second)¹	1.08 (1.0-0.17)	0.048	1.08 (1.0-0.17)	0.48
Apixaban-peak (up 1 ng/mL)	1.0 (0.99-1.01)	0.867
PFA (closure time) (up 1 second)	1.01 (0.99-1.02)	0.430

¹After administration of apixaban.

CT: Clotting time; PFA: Platelet Function Analyzer; OR: Odds ratio; CI: Confidence interval.

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Table 6 Apixaban levels and clotting time-pre and clotting time-post drug administration in the four drug dose regimens as described in methods, mean (minimum-maximum)

Parameter	1	2	3	4	P value
Apx-trough	12 (11-13}	34 (6-89)	131 (40-285)	176 (93-269)	0.020
Apx-peak	71 (55-87)	125 (68-202)	194 (90-330)	248 (220-274)	0.048
CT-pre¹	72 (67-77)	70 (65-76)	92 (71-139)	92 (86-103)	0.099
CT-post²	118 (116-120)	84 (74-104)	103 (75-156)	106 (102-113)	0.323

¹Prior administration of apixaban.

²After administration of apixaban.

Apx-trough and Apx-peak, apixaban peak and trough levels respectively. Apx: Apixaban; CT: Clotting time.

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Citation: Bacharaki D, Kyriakou E, Sardeli A, Nikolopoulos P, Triantaphyllis G, Drakou A, Makris F, Spanou E, Triantou E, Haviaras E, Fatourou A, Poulis A, Tsantes A, Kyriazis J, Lionaki S. Bleeding prediction by rotational thromboelastometry in chronic hemodialysis patients with non-valvular atrial fibrillation on apixaban. World J Cardiol 2025; 17(12): 112046
URL: https://www.wjgnet.com/1949-8462/full/v17/i12/112046.htm
DOI: https://dx.doi.org/10.4330/wjc.v17.i12.112046