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What is the optimal management of thromboprophylaxis after liver transplantation regarding prevention of bleeding, hepatic artery or portal vein thrombosis? A systematic review of the literature and expert panel recommendations
Kirchner VA, O'Farrell B, Imber C, McCormack L, Northup PG, Song GW, Spiro M, Raptis DA, Durand F
Clinical transplantation. 2022;:e14629
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Abstract
BACKGROUND A key tenet of clinical management of patients post liver transplantation (LT) is the prevention of thrombotic and bleeding complications. This systematic review investigated the optimal management of thromboprophylaxis after LT regarding portal vein thrombosis (PVT) or hepatic artery thrombosis (HAT) and prevention of bleeding. METHODS Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. Seven databases were used to conduct extensive literature searches focusing on the use of anticoagulation in LT and its impact on the following outcomes: PVT, HAT, and bleeding. (CRD42021244288) RESULTS Of the 2,478 articles/abstracts screened, 16 studies were included in the final review. All articles were critically appraised by a panel of independent reviewers. There was wide variation regarding the anticoagulation protocols used. Thromboprophylaxis with therapeutic doses of heparin/Vitamin K antagonist combination did not decrease the risk of de novo or the recurrence of PVT but was associated with an increased risk of bleeding in some studies. Only the use of aspirin resulted in a small but significant decrease in the incidence of HAT post-LT, yet it did not increase the risk of bleeding. CONCLUSIONS Based on existing data and expert opinion, thromboprophylaxis at therapeutic or prophylactic dose is not recommended for prevention of de novo PVT following LT in patients not at high risk. Aspirin should be considered as the standard of care following LT to prevent HAT. Thromboprophylaxis should be strongly considered in recipients at risk of HAT and PVT following LT. This article is protected by copyright. All rights reserved.
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Viscoelastic versus conventional coagulation tests to reduce blood product transfusion in patients undergoing liver transplantation: A systematic review and meta-analysis
Aceto P, Punzo G, Di Franco V, Teofili L, Gaspari R, Wolfango Avolio A, Del Tedesco F, Posa D, Lai C, Sollazzi L
European journal of anaesthesiology. 2022
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Editor's Choice
Abstract
BACKGROUND Recent literature suggests viscoelastic test (VET)-guided transfusion management could be associated with reduced blood product administration in patients undergoing liver transplantation. OBJECTIVES To assess the effectiveness of coagulation management guided by VETs compared with conventional coagulation tests (CCTs) in reducing blood product transfusion in patients undergoing liver transplantation. DESIGN Systematic review and meta-analysis of randomised (RCTs) and nonrandomised clinical trials performed according to PRISMA guidelines. The protocol was previously published (PROSPERO CRD42021230213). DATA SOURCES The Cochrane Central Library, PubMed/MEDLINE, Embase and the Transfusion Evidence Library were searched up to 30th January 2022. ELIGIBILITY CRITERIA Setting: operating room. Patients: liver transplantation recipients. Intervention: use of VETs versus CCTs. Main outcome measures: the primary outcome was the mean number of transfused units for each blood product including red blood cells (RBCs), fresh frozen plasma (FFP), platelets (PLTs) and cryoprecipitate. Secondary outcomes included mortality rate, intensive care unit (ICU) and hospital length of stay (LOS). RESULTS Seventeen studies (n = 5345 patients), 15 observational and two RCTs, were included in this review. There was a mean difference reduction in RBCs [mean difference: -1.40, 95% confidence interval (95% CI), -1.87 to -0.92; P < 0.001, I2 = 61%) and FFP units (mean difference: -2.98, 95% CI, -4.61 to -1.35; P = < 0.001; I2 = 98%) transfused in the VETs group compared with the CCTs one. A greater amount of cryoprecipitate was administered in the VETs group (mean difference: 2.71, 95% CI, 0.84 to 4.58; P = 0.005; I2 = 91%). There was no significant difference in the mean number of PLT units, mortality, hospital and ICU-LOS. CONCLUSION Our meta-analysis demonstrated that VETs implementation was associated with reduced RBC and FFP consumption in liver transplantation patients without effects on mortality and hospital and ICU-LOS. The certainty of evidence ranged from moderate to very low. Further well conducted RCTs are needed to improve the certainty of evidence.
PICO Summary
Population
Patients undergoing liver transplantation (17 studies, n= 5,345).
Intervention
Coagulation management guided by viscoelastic tests (VETs group).
Comparison
Conventional coagulation tests (CCTs group).
Outcome
There was a mean difference reduction in red blood cells (mean difference: -1.40, 95% confidence interval (95% CI) -1.87 to -0.92, I2 = 61%) and fresh frozen plasma units (mean difference: -2.98, 95% CI -4.61 to -1.35; I2 = 98%) transfused in the VETs group compared with the CCTs group. A greater amount of cryoprecipitate was administered in the VETs group (mean difference: 2.71, 95% CI, 0.84 to 4.58; I2 = 91%). There was no significant difference in the mean number of platelets units, mortality, hospital and intensive care unit (ICU) and hospital length of stay (LOS).
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Viscoelastometric versus standard coagulation tests to guide periprocedural transfusion in adults with cirrhosis: A meta-analysis of randomized controlled trials
Tangcheewinsirikul N, Moonla C, Uaprasert N, Pittayanon R, Rojnuckarin P
Vox sanguinis. 2021
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Editor's Choice
Abstract
BACKGROUND AND OBJECTIVES Due to rebalanced haemostasis in cirrhosis, viscoelastometric testing (VET) is more accurate than standard coagulation tests (SCTs) in preprocedural haemostatic evaluation, resulting in decreased unnecessary transfusion. We aimed to determine the impact of VET-guided strategy on postprocedural bleeding, periprocedural transfusion rates and quantities, transfusion-related adverse events (TRAEs), lengths of stay (LOS) and mortality from randomized controlled trials (RCTs) of cirrhotic patients. METHODS PubMed and EMBASE were searched for RCTs comparing VET-guided with SCT-guided transfusion in cirrhotic adults undergoing esophagogastroduodenoscopy, liver transplantation or other invasive interventions. Using random-effects models, the pooled risk ratios (RRs) and/or mean differences (MDs) of postprocedural bleeding-free events and the other outcomes were estimated alongside 95% confidence intervals (CIs). RESULTS Of seven included RCTs (n = 421; 72.2% men; mean age 49.1 years), VET-guided transfusion did not change postprocedural bleeding-free statuses (RR 1.05; 95% CI 0.94-1.17). However, VET-based algorithms decreased the rates of fresh frozen plasma (FFP; RR 0.52; 95% CI 0.35-0.77) and platelet transfusions (RR 0.34; 95% CI 0.16-0.73), the quantities of transfused FFP (MD -1.39 units; 95% CI -2.18 to -0.60), platelets (MD -1.06 units; 95% CI -2.01 to -0.12) and cryoprecipitate (MD -7.13 units; 95% CI -14.20 to -0.07) and the risk of TRAEs (RR 0.42; 95% CI 0.27-0.65). The overall mortality rates and LOS were not significantly different between two groups. CONCLUSION Compared with conventional SCT-guided, VET-guided strategy decreases periprocedural plasma and platelet transfusions and TRAEs, without increasing haemorrhagic complications, LOS or mortality in cirrhosis.
PICO Summary
Population
Patients with cirrhosis undergoing esophagogastroduodenoscopy, liver transplantation or other invasive interventions (7 studies, n= 421).
Intervention
Viscoelastometric testing (VET) guided transfusion.
Comparison
Standard coagulation testing (SCT) guided transfusion.
Outcome
VET-guided transfusion did not change post-procedural bleeding-free statuses. However, VET-based algorithms decreased the rates of fresh frozen plasma (FFP) and platelet transfusions, the quantities of transfused FFP (MD -1.39 units), platelets (MD -1.06 units) and cryoprecipitate (MD -7.13 units) and the risk of transfusion-related adverse events. The overall mortality rates and lengths of stay were not significantly different between two groups.
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Correlation between plasma fibrinogen and FIBTEM thromboelastometry during liver transplantation: a comprehensive assessment
Blasi A, Sabate A, Beltran J, Costa M, Reyes R, Torres F
Vox Sanguinis. 2017;112((8):):788-795
Abstract
BACKGROUND Thromboelastometry may reduce red blood cell (RBC) transfusion in liver transplantation (LT). Fibrinogen concentration is a primary determinant of FIBTEM maximum clot firmness (MCF), but several factors could affect the correlation between FIBTEM MCF and fibrinogen values. We aimed to investigate (1) the concordance between fibrinogen level and FIBTEM MCF and (2) the association of fibrinogen level and FIBTEM MCF with RBC transfusion during LT. METHODS A post hoc analysis of data from a randomized, multicentre, double-blind, saline/fibrinogen trial was used (NCT01539057). A total of 86 adult patients were included. RESULTS The Lin concordance coefficient (LCC) between FIBTEM MCF and fibrinogen levels with the model formula 1.3679 + 0.05414* FIBTEM MCF was poor overall (LLC [95% CI]: 0.387 [0.340 to 0.432]) and moderate for the preperfusion period (LLC [95% CI]: 0.789 [0.747 to 0.824]), but very poor for the postreperfusion period (LLC [95% CI] 0.170 [0.105 to 0.233]). The model assessed for RBC transfusion for FIBTEM MCF showed an area under the curve of 0.788 [0.745-0.832]. Patients with FIBTEM MCF values <8 mm had a significantly higher likelihood of receiving RBC than patients with higher values. (OR [95% CI]: 2.08 [1.30-3.33], P = 0.002). FIBTEM MCF values over 10 mm do not appear to reduce the likelihood of RBC transfusion. CONCLUSION FIBTEM MCF is not a good indicator of plasma fibrinogen values after graft reperfusion. FIBTEM MCF >8 mm during the LT procedure is associated with less RBC transfusion. FIBTEM MCF values over 10 mm could lead to unnecessary fibrinogen administration.
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Thrombelastography-guided blood product use before invasive procedures in cirrhosis with severe coagulopathy: a randomized, controlled trial
De Pietri L, Bianchini M, Montalti R, De Maria N, Di Maira T, Begliomini B, Gerunda GE, di Benedetto F, Garcia-Tsao G, Villa E
Hepatology. 2016;63((2)):566-73.
Abstract
UNLABELLED Bleeding is a feared complication of invasive procedures in patients with cirrhosis and significant coagulopathy (as defined by routine coagulation tests) and is used to justify preprocedure use of fresh frozen plasma (FFP) and/or platelets (PLT). Thromboelastography (TEG) provides a more comprehensive global coagulation assessment than routine tests (international normalized ratio [INR] and platelet count), and its use may avoid unnecessary blood product transfusion in patients with cirrhosis and significant coagulopathy (defined in this study as INR >1.8 and/or platelet count <50 x 10(9) /L) who will be undergoing an invasive procedure. Sixty patients were randomly allocated to TEG-guided transfusion strategy or standard of care (SOC; 1:1 TEG:SOC). The TEG group would receive FFP if the reaction time (r) was >40 min and/or PLT if maximum amplitude (MA) was <30 mm. All SOC patients received FFP and/or PLT per hospital guidelines. Endpoints were blood product use and bleeding complications. Baseline characteristics of the two groups were similar. Per protocol, all subjects in the SOC group received blood product transfusions versus 5 in the TEG group (100% vs. 16.7%; P<0.0001). Sixteen SOC (53.3%) received FFP, 10 (33.3%) PLT, and 4 (13.3%) both FFP and PLT. In the TEG group, none received FFP alone (P<0.0001 vs. SOC), 2 received PLT (6.7%; P=0.009 vs. SOC), and 3 both FFP and PLT (not significant). Postprocedure bleeding occurred in only 1 patient (SOC group) after large-volume paracentesis. CONCLUSIONS In patients with cirrhosis and significant coagulopathy before invasive procedures, TEG-guided transfusion strategy leads to a significantly lower use of blood products compared to SOC (transfusion guided by INR and platelet count), without an increase in bleeding complications. Remarkably, even in patients with significant coagulopathy, postprocedure bleeding was rare, indicating that TEG thresholds should be reevaluated. (Hepatology 2016;63:566-573).Copyright © 2015 by the American Association for the Study of Liver Diseases.
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Evaluation of hemostatic factors in patients undergoing major hepatic resection and other major abdominal surgeries
Tapper EB, Tanaka KA, Sarmiento JM
The American Surgeon. 2011;77((9):):1188-93.
Abstract
The aim of this study was to evaluate the role for additional testing of coagulation in perioperative management of patients undergoing major hepatic resection. Major outcome measures were perioperative measurements of hemostatic factors (activated partial prothrombin time [aPTT], prothrombin time/international normalized ratio, fibrinogen, antithrombin-III). We conducted a prospective, single-blind study comparing hemostatic factors in patients undergoing major hepatectomy, Whipple procedures, and other gastrointestinal operations. Ninety-five consecutive patients were enrolled. No values differed significantly at baseline. Immediately postoperative, only international normalized ratio was significantly lower comparing major hepatectomy with Whipple (P < 0.005) and other procedures (P < 0.0032). Twenty-four hours postoperative, antithrombin-III was lower for major hepatectomy than Whipple (P < 0.028) and others (P < 0.0001); fibrinogen was lower compared with Whipple (P < 0.014) and others (P < 0.0009); international normalized ratio was lower to compared with Whipple (P < 0.0001) and others (P < 0.0001). aPTT measurements never differed significantly between groups at any time. Antithrombin-III and fibrinogen only correlated with international normalized ratio and aPTT for the other procedures. Additional hemostatic values beyond the standard evaluations of aPTT and international normalized ratio are needed to better assess patients undergoing major hepatic surgery.
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Thromboelastography-guided transfusion decreases intraoperative blood transfusion during orthotopic liver transplantation: randomized clinical trial
Wang SC, Shieh JF, Chang KY, Chu YC, Liu CS, Loong CC, Chan KH, Mandell S, Tsou MY
Transplantation Proceedings. 2010;42((7):):2590-3.
Abstract
OBJECTIVE To test in a prospective randomized study the hypothesis that use of thromboelastography (TEG) decreases blood transfusion during major surgery. MATERIAL AND METHODS Twenty-eight patients undergoing orthotopic liver transplantation were recruited over 2 years. Patients were randomized into 2 groups: those monitored during surgery using point-of-care TEG analysis, and those monitored using standard laboratory measures of blood coagulation. Specific trigger points for transfusion were established in each group. RESULTS In patients monitored via TEG, significantly less fresh-frozen plasma was used (mean [SD], 12. 8 [7. 0] units vs 21. 5 [12. 7] units). There was a trend toward less blood loss in the TEG-monitored patients; however, the difference was not significant. There were no differences in total fluid administration and 3-year survival. CONCLUSION Thromboelastography-guided transfusion decreases transfusion of fresh- frozen plasma in patients undergoing orthotopic liver transplantation, but does not affect 3-year survival.