Safety of laparoscopic surgery in digestive diseases with special reference to antithrombotic therapy: A systematic review of the literature

Table 1 Reported data concerning bleeding complications of "basic" abdominal surgery in patients with antithrombotic therapy (antiplatelet therapy and/or anticoagulation therapy)

First author of the reports	Year	Surgery type	Drug use and exposure	Bleeding events	TE, mortality
Laparoscopic surgery (overall)
Fujikawa[10]	2013	Abdominal laparoscopic surgery (cholecystectomy (mostly), appendectomy, surgery for GI malignancy, liver resection, splenectomy etc)	Patients with continued use of ASA (n = 52)	PBC 0% in continued ASA vs 2.5% in discontinuation vs 0.7% in control (P = 0.987)	TE 0% in continued ASA vs 0.6% in discontinued ASA vs 0.2% in control (P = 0.625)
			Patients with discontinuation of APT (n = 160)		Only one mortality in continued ASA group (1.9%)
			Patients not on APT (control, n = 863)
Laparoscopic cholecystectomy
Ercan[11]	2010	Laparoscopic cholecystectomy (only elective)	Patients with ACT (w/ bridging, n = 44)	PBC 25% in ACT vs 1.5% in control (P < 0.001)	(not mentioned)
			Patients without ACT (control, n = 1377)	One mortality due to severe bleeding
Ono[12]	2013	Laparoscopic cholecystectomy (n = 270) or Laparoscopic colorectal cancer resection (n = 218)	Patients with continued ASA (n = 52)	SBL 27 mL in continued ASA vs 17 mL in control (P = 0.430)	No mortality in both groups
			Patients without ASA (control, n = 436)
Anderson[13]	2014	Laparoscopic cholecystectomy (elective and emergency)	Patients with continued clopidogrel (n = 36)	No difference in SBL (49 g vs 47 g, P = 0.85)	No TE in both groups
			Matched patients without clopidogrel (control, n = 36)	PBC 0% in clopidogrel vs 2.8% in control (P = 0.31)	No mortality in both groups
Noda[14]	2014	Early laparoscopic cholecystectomy for acute cholecystitis	Patients with continued use of ATT (n = 21)	No conversion to open surgery	No mortality in both groups
			Patients without ATT (n = 162)	No PBC in both groups
Joseph[15]	2015	Emergency laparoscopic cholecystectomy	Patients with continued use of APT (n = 56), including those with preop Plt transfusion (n = 12)	SBL ≥ 100 mL 14.3% in continued ASA vs 9% in control (P = 0.50)	No difference in the rates of overall postop complications (8.9% vs 7.1%, P = 0.80)
			Patients without APT (control, n = 56)		No mortality in both groups
Fujikawa[16]	2017	Emergency cholecystectomy including 106 laparoscopic surgery for acute cholecystitis	Patients with continued use of APT (n = 89)	SBL ≥ 500 mL 12% in continued APT vs 5% in control (P = 0.240)	TE 1.1% in continued APT vs 0% in control (P = 0.37)
			Patients without APT (control, n = 154)	PBC 7% in multiple APT vs 3% in single APT vs 0.6% in control (P = 0.027)	No mortality in both groups
Sakamoto[17]	2017	Laparoscopic cholecystectomy (only elective operation)	Patients with continued single APT (n = 49)	SBL ≥ 200 mL 4.7% in continued APT vs 4.7% in discontinued APT vs 1.5% in control (P = 0.064)	TE 0% in continued APT vs 0.9% in discontinued APT vs 0.2% in control (P = 0.296)
			Patients with discontinuation of APT (n = 106)	PBC 0% in continued APT vs 0.9% in discontinued APT vs 0.2% in control (P = 0.022)	No mortality in any group
			Patients not on APT (control, n = 653)
Yun[18]	2017	Laparoscopic cholecystectomy (elective vs emergency) for acute cholecystitis	Patients with continued use of ATT (almost APT, n = 22)	SBL ≥ 100mL 13.6% in continued ATT vs 22.2% in control (P = 0.613)	One case of TE (2.2%) in control
			Patients with discontinued ATT (almost APT, control, n = 45)		Mortality 4.6% in continued ATT vs 2.2% in control (P > 0.999)
Laparoscopic appendectomy
Chechik[19]	2011	Appendectomy including laparoscopic appendectomy (n = 78)	Patients with continued APT (n = 39)	No difference in SBL or PBC between the groups	No mortality in both groups
			Patients without APT (control, n = 140)
Pearcy[20]	2017	Laparoscopic appendectomy (urgent only)	Patients with continued APT (n = 287)	No difference in SBL (31 g vs 26 g) or blood transfusion rate (1% vs 0%) between the groups	Two cases of TE (MI) in continued APT (0.7%)
			Matched patients without APT (control, n = 287)		No difference in the rates of mortality (1% vs 0%, P = 0.12)

ATT: Antithrombotic therapy; APT: Antiplatelet therapy, ACT: Anticoagulation therapy; TE: Thromboembolism; SBL: Surgical blood loss; PBC: Postoperative bleeding complications; ASA: Aspirin; GE: Gastroenterological; MI: Myocardial infarction.

Table 2 Reported data concerning bleeding complications of "advanced" abdominal surgery in patients with antithrombotic therapy (antiplatelet therapy and/or anticoagulation therapy)

First author of the reports	Year	Surgery type	Drug use and exposure	Bleeding events	TE, mortality
Laparoscopic liver resection
Fujikawa[24]	2017	Laparoscopic liver resection vs open liver resection	Patients with ATT (n = 100)	SBL ≥ 500 mL 23% in those with ATT vs 27% in control (P = 0.468)	TE 1% in ATT vs 1.3% in control (P = 0.310)
			Patients without ATT (control, n = 158)	PBC 4.6% in those with ATT vs 4.3% in control	Mortality 1% in ATT vs 0% in control (P = 0.350)
Laparoscopic colorectal cancer resection
Ono[12]	2013	Laparoscopic colorectal cancer resection (n = 218) or laparoscopic cholecystectomy (n = 270)	Patients with continued ASA (n = 52)	SBL 27 mL in continued ASA vs 17 mL in control (P = 0.430)	No mortality in both groups
			Patients without ASA (control, n = 436)
Shimoike[21]	2016	Colorectal cancer surgery including laparoscopic surgery (n = 191)	Patients with APT (n = 148)	PBC 0.7% in those with APT vs 0.9% in control (P = 1.000)	TE 0.7% in APT vs 0% in control (P = 0.301)
			Patients without APT (control, n = 343)		No mortality in both groups
Laparoscopic gastrectomy
Takahashi[22]	2017	Laparoscopic gastrectomy	Patients with ATT (continued in high risk, n = 12)	No difference in SBL or PBC between the groups	No difference in overall complications between the groups
			Patients without ATT (n = 34)		No mortality in both groups
Gerin[23]	2015	Laparoscopic sleeve gastrectomy	Patients with ACT (n = 15)	PBC 6.7% in ACT vs 3.3% in control (P = 0.60)	No mortality in both groups
			Matched patients without ACT (control, n = 30)

ATT: Antithrombotic therapy; APT: Antiplatelet therapy; ACT: Anticoagulation therapy; TE: Thromboembolism; SBL: Surgical blood loss; PBC: Postoperative bleeding complications; ASA: Aspirin; HBP: Hepatobiliary and pancreas.

Table 3 Types, specific agents, and acting duration of commonly used antithrombotic drugs

Class of agents	Type	Specific agents	Duration of action
Antiplatelets
	Thienopyridines	Clopidogrel (Plavix), Ticlopidine (Panardine), Prasugrel (Effient)	5-7 d1
	Type III PDE inhibitor	Cilostazol (Pretal)	2 d
	Acetylsalicylic acid	Aspirin	7-10 d
	Other NSAIDs	Ibuprofen (Brufen, Advil), Loxoprofen (Loxonin), Diclofenac (Voltaren), etc	Varies
Anticoagulants
	Vitamin K antagonist	Warfarin (Coumadin)	5 d
	Heparin derivatives	Fondaparinux (Arixtra)	1.5-2 d
	DOACs
	Direct thrombin inhibitor	Dabigatran (Pradaxa)	1-2 d
	Factor Xa inhibitors	Rivaroxaban (Xarelto), Apixaban (Eliquis), Edoxaban (Lixiana)	1-2 d

¹In ticlopidine, duration of action is 10-14 d. PDE: Phosphodiesterase; NSAID: Non-steroidal anti-inflammatory drug; DOAC: Direct-acting oral anticoagulant.