Postoperative bleeding in patients on antithrombotic therapy after gastric endoscopic submucosal dissection

Table 1 Clinicopathological features and treatment outcomes of all 2094 patients (2434 lesions and 2378 ulcers) n (%)

Age (mean ± SD, yr)	72 ± 6.9
Gender
Male	1786 (75.1)
Female	592 (24.9)
Location
U	412 (17.5)
M	742 (31.2)
L	122 (51.5)
Morphology
Protruded	1042 (43.8)
Flat/depressed	1336 (56.2)
Specimen size, (mean ± SD, mm)	39 ± 9.8
Depth of invasion
M	2227 (93.7)
SM	151 (6.3)
Ulcerative findings
(+)	203 (8.5)
(-)	2175 (91.5)
Anticoagulant agents
(+)	447 (18.8)
(-)	1931 (81.2)
En-bloc resection	99.2%
R0+curative resection	91.9%
Mean procedure time ± SD (min)	49 ± 30.1
Complications
Perforation	74 (3.1)
Delayed perforation	2 (0.8)
Delayed bleeding	122 (5.1)
Thromboembolism	0

Table 2 Univariate analysis of risk factors of delayed bleeding n (%)

	n = 2378	Delayed bleeding		P value	OR	95%CI
		(+) n = 122	(-) n = 2256
Age (mean ± SD, yr)		71.5 ± 8.7	71.1 ± 8.8	0.6222	1.005	0.984-1.027
Gender
Male	1786 (75.1)	106 (5.9)	1680 (94.1)	0.0021	2.271	1.331-3.875
Female	24.9 (592)	16 (2.7)	576 (97.3)
Location
U	412 (17.3)	17 (4.1)	395 (95.9)		Reference	1.0
M	742 (31.2)	40 (5.4)	702 (94.6)	0.342	1.303	0.755-2.250
L	1224 (51.5)	65 (5.3)	1159 (94.7)	0.344	1.324	0.741-2.366
Morphology
Protruded	1042 (43.8)	49 (4.7)	993 (95.3)	0.4041	0.854	0.589-1.238
Flat/depressed	1336 (56.2)	73 (5.5)	1263 (94.5)
Specimen size (mean ± SD, mm)	38.9 ± 2.2	44.4 ± 15.1	38.9 ± 13.1	< 0.0012	1.025	1.014-1.037-
Depth of invasion
M	2227 (93.7)	109 (4.9)	2118 (95.1)	0.0451	1.830	1.004-3.336
SM	151 (6.3)	13 (8.6)	138 (91.4)
Ulcerative findings
(+)	203 (8.5)	12 (5.9)	191 (94.1)	0.5981	1.179	0.638-2.179
(-)	2175 (91.5)	110 (5.1)	2065 (94.9)
Anticoagulant agents
(+)	447 (18.8)	46 (10.3)	401 (89.7)	< 0.0011	2.800	1.911-4.101
(-)	1931 (81.2)	76 (3.9)	1855 (96.1)
En-bloc resection rate	99.2%	99.1%	99.2%	0.979	0.973	0.129-7.329
R0+curative resection rate	91.9%	95.1%	97.1%	0.198	1.744	0.740-4.017
Median procedure time (min)	49 ± 30.1	50 ± 30.8	50 ± 32.2	0.8852	1.033	0.840-2.354

¹χ² test;

²t-test.

Table 3 Multivariate analysis of risk factors of delayed bleeding

	P value	OR	95%CI
Male	0.007	2.103	1.224-3.611
Median specimen size	< 0.001	1.025	1.013-1.037
SM	0.187	1.516	0.817-2.812
Anticoagulant agents (+)	< 0.001	2.643	1.796-3.889

Table 4 Univariate analysis of risk factors for delayed bleeding by each antithrombotic agent n (%)

	Delayed bleeding		P value1	OR	95%CI
	(+)	(-)
Aspirin
(+) (n = 211)	12 (5.7)	199 (94.3)	0.224	1.472	0.787-2.753
(-) (n = 1931)	76 (3.9)	1855 (96.1)
Thienopyridine
(+) (n = 19)	0 (0)	19 (100)	0.379	0.990	0.985-0.994
(-) (n = 1931)	76 (3.9)	1855 (96.1)
Warfarin
(+) (n = 17)	1 (5.9)	16 (94.1)	0.498	1.525	0.200-11.653
(-) (n = 1931)	76 (3.9)	1855 (96.1)
DOAC
(+) (n = 18)	1 (5.6)	17 (94.4)	0.725	1.436	0.189-10.930
(-) (n = 1931)	76 (3.9)	1855 (96.1)
Others
(+) (n = 70)	3 (4.3)	67 (95.7)	0.883	1.093	0.336-3.554
(-) (n = 1931)	76 (3.9)	1855 (96.1)
HBT
(+) (n = 39)	6 (15.4)	33 (84.6)	< 0.01	4.438	1.805-10.911
(-) (n = 1931)	76 (3.9)	1855 (96.1)
DAPT/multidrug combination
(+) (n = 75)	23 (30.7)	52 (69.3)	< 0.01	10.796	6.280-18.558
(-) (n = 1931)	76 (3.9)	1855 (96.1)

¹χ² test. DOAC: Direct oral anticoagulants; HBT: Heparin bridging therapy; DAPT: Dual antiplatelet therapy.

Table 5 Multivariate analysis of risk factors for delayed bleeding by each antithrombotic agent

	P value	OR	95%CI
HBT	0.002	4.244	1.736-10.380
DAPT/multidrug combination	< 0.001	10.325	6.060-17.593

HBT: Heparin bridging therapy; DAPT: Dual antiplatelet therapy.

Table 6 Investigation of rate of bleeding based on withdrawal or continuation of antithrombotic agent n (%)

	Delayed bleeding		P value1	OR	95%CI
	(+)	(-)
Control group/withdrawal group
Control (n = 1931)	76 (3.9)	1855 (96.1)	< 0.01	0.472	0.308-0.725
Withdrawal (n = 401)	32 (8.0)	369 (92.0)
Withdrawal group/continuation group
Withdrawal (n = 401)	32 (8.0)	369 (92.0)	< 0.01	5.045	2.445-10.411
Continuation (n = 46)	14 (30.4)	32 (69.6)

¹χ² test.

Table 7 Investigation of bleeding time by each drug

	Bleeding (+) n = 46		P value1	OR	95%CI
	Early phase	Late phase
Aspirin (n = 12)	6	6	0.477	0.619	0.164-2.332
Thienopyridine (n = 0)	0	0	-	-	-
Warfarin (n = 7)	6	1	0.015	0.083	0.009-0.767
DOAC (n = 1)	0	1	1.000	1.038	0.964-1.118
Others (n = 3)	2	1	0.561	0.327	0.027-3.892
HBT (n = 6)	5	1	0.068	0.108	0.011-1.015
DAPT/multidrug combination (n = 23)	5	18	0.007	5.600	1.530-20.492

¹Fisher’s exact test. DOAC: Direct oral anticoagulants; HBT: Heparin bridging therapy; DAPT: Dual antiplatelet therapy.