Review
Copyright ©The Author(s) 2018.
World J Gastroenterol. Jul 21, 2018; 24(27): 2931-2948
Published online Jul 21, 2018. doi: 10.3748/wjg.v24.i27.2931
Table 1 Balance of antihemostatic and prohemostatic drivers in the cirrhotic patient
Anti-hemostatic driversPro-hemostatic drivers
Primary hemostasisAbnormal platelet functionElevated vWF
ThrombocytopeniaReduced ADAMTS 13
Decreased production of thrombopoietinPlatelet hyperreactivity
CoagulationReduced synthesis of factors II, V, VII, IX, X, and XIElevated factor VIII
Vitamin K deficiencyReduced anticoagulant protein C, protein S, antithrombin III
Hypo-dysfibrinogenemiaProcoagulant changes in fibrin structure
FibrinolysisLow α2-antiplasmin,Low plasminogen
factor XIII, and TAFIHigh PAI
Elevated tPA
Table 2 Different thromboprophylaxis protocols for postoperative arterial and venous thrombosis in liver transplant patients
AuthorsType of studyDrug usedTarget populationNumber PtsPVTHATBleedingObservations
Blasi 2016[61]Retrospective study No controlsEnoxaparin not routinely, unless intraoperative. thrombectomy or the patient was under anticoagulant treatment before LT. No thromboprophylaxis if the platelets are under 30 × 109/L.Adult LT3288 (2.4%)NANot reported5/8 patients with PVT did not receive prophylaxis, and the other 3 received it days after LT or in only a few doses
Kaneko 2005[71]Prospective study No controlsDalteparin administration adjusted with reference to the ACT (130-160 s)Adult Living-donor LT1281 PVT (0.78%) and 1 (0.78%) PVT + HAT2 HAT (1.5%) and 1 HAT + PVT (0.78%)11 (8.5%) surgical revisions and 8 (6.25%) patients with hemorrhages complications treated conservativelyHigh hemorrhage complication rate in this series indicates that a lower target ACT range may be preferable in the second post-operative week.
Gad 2016[74]Retrospective study No controlsHeparin infusion up to 180-200 units/kg/day adjusted with reference to the ACT (target levels, 180-200 s) and/or the aPTT (target levels, 50-70 s).Adult and pediatric living-donor LT1865 (2.3%)4 HAT (1.8%) 4 HAT and PVT (1.8%)4 (1.8%)Pre-LT PVT may deserve more intensive anticoagulation therapy
Sugawara 2002[76]Prospective study No ControlsLMWH, ATIII, prostaglandin E1 (0.01 g/kg/h) and a protease inhibitorAdult Living-donor LT1724 (2.3%) both PVT + HAT7 (4.0%)Not consideredThe authors’ strategy against HAT is aimed to correct the imbalance between the coagulation and anticoagulation systems
Mori 2017[80]Prospective study No controlsHeparin infusion at the dose of 5 U/kg/h during the first week after LTAdult Living-donor LT282 total patients; 48 patients with pre-existing PVT; number of patient with thromboprophylaxis not cited8 (17%)NANot consideredThe basic protocol after LDLT does not provide anticoagulant therapy. Only patients with good coagulation (INR) < 1.5 or slow portal flow (velocity < 10 cm/s) and intraoperative portal reconstruction for PVT were administered intravenous heparin. The aim of this study was to determine the risk factors that influence the incidence of DVT/PE and the effectiveness of prophylaxis
Yip 2016[73]Retrospective case control studySubcutaneous heparin (5000 U) every 8 hAdult LT999 total patients; 288 patients with thromboprophylaxis from 2011Not consideredNot consideredNAThe aim of this study was to determine the risk factors that influence the incidence of DVT/PE and the effectiveness of prophylaxis
Uchikawa 2009[75]Prospective case control studyContinuous i.v. Dalteparin infusion administered in the anhepatic phase to maintain the ACT levels from 140 to 150 seconds (Gr.A) vs continuous i.v Dalteparin infusion administered immediately after the operation and adjusted depending on clinical findings (Gr.B)Adult Living-donor LT42 total patients (10 vs 32)0 % in Gr. B 5 (15.6%) in Gr. A0 % in Gr. B 5 (15.6%) in Gr. A0% in Gr. B 1 (3.1%) in Gr. AThe study evaluated the advantage of ACT as a reliable tool for bedside monitoring of LMWH anticoagulant effects during and following LDLT
Stange 2003[72]Retrospective study No controlsUFH 5000 IU over 24 h beginning 6 h postoperatively, for 14 dAdult Living-donor LT1192Not evaluated14 (1.17%)3 (0.2%) bleeding episodes not apparently related to UFHThe authors analyzed the incidence, clinical presentation, therapeutic options, and outcome of hepatic artery thrombosis (HAT)
Wolf DC, 1997[77]Retrospective case control study81 mg oral aspirin in adult and 40 mg in children from postoperative day 1Adult and pediatric LT499 total patients (354 vs 175)Not evaluated10 (2.9%) vs 6 (3.6%) in the not treated group89 (16.8%) gastrointestinal bleeding 66 treated vs 23 not treated patientsThe spontaneous or invasive maneuver-related bleeding episodes were more frequent in the treated group
Vivarelli 2007[78]Retrospective case control study100 mg aspirinAdult LT838 total patients (236 treated vs 592 not treated)Not evaluated1/236 (0.4%) treated patients vs 13/592 (2.2%) not treated patients0%The aim of this study was to determine the safety and efficacy of aspirin therapy on late HAT
Shay 2013[79]Retrospective case control study325 mg aspirinAdult LT469 total patients (165 treated vs 304 not treated)6/304 (2%) not treated patients vs 1/165 patients treated (0.6%)15/304 patients (4.9%) vs 5/165 (3%) patients overall HAT (early and late) in the control and treated groupSimilar bleeding rates between the two groupsThe aim of this study was to determine the safety and efficacy of early aspirin therapy on clinical outcomes
Table 3 Possible conditions warranting thromboprophylaxis in the postoperative period of liver transplant recipients
Living-donor liver transplant and split liver
Surgical difficulties and complex vessel reconstruction
Presurgical portal vein thrombosis
Intraoperative portal or hepatic artery thrombectomy
Hypoplastic portal vein
Jump graft artery reconstruction
Cholestatic recipient diseases and Budd-Chiari disease
Non-alcoholic fatty liver disease/non-alcoholic steatohepatitis
Small or multiple recipient arteries
Low portal or arterial blood flow intraoperatively