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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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The Use of Thromboelastography in Percutaneous Coronary Intervention and Acute Coronary Syndrome in East Asia: A Systematic Literature Review
Xu O, Hartmann J, Tang YD, Dias J
Journal of clinical medicine. 2022;11(13)
Abstract
Dual antiplatelet therapy (DAPT), alongside percutaneous coronary intervention (PCI), is central to the prevention of ischemic events following acute coronary syndrome (ACS). However, response to therapy can vary due to several factors including CYP2C19 gene variation, which shows increased prevalence in East Asian populations. DAPT responsiveness can be assessed using techniques such as light transmission aggregometry (LTA), VerifyNow(®) and thromboelastography with the PlateletMapping(®) assay, and there is increasing focus on the utility of platelet function testing to guide individualized treatment. This systematic literature review of one English and three Chinese language databases was conducted to evaluate the evidence for the utility of thromboelastography in ACS/PCI in East Asia. The search identified 42 articles from the English language and 71 articles from the Chinese language databases which fulfilled the pre-determined inclusion criteria, including 38 randomized controlled trials (RCTs). The identified studies explored the use of thromboelastography compared to LTA and VerifyNow in monitoring patient responsiveness to DAPT, as well as predicting ischemic risk, with some studies suggesting that thromboelastography is better able to detect low DAPT response than LTA. Other studies, including one large RCT, described the use of thromboelastography in guiding the escalation of DAPT, with some evidence suggesting that such protocols reduce ischemic events without increasing the risk of bleeding. There was also evidence suggesting that thromboelastography can be used to identify individuals with DAPT hyporesponsiveness genotypes and could potentially guide treatment by adjusting therapy in patients depending on responsiveness.
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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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Utility of Viscoelastic Tests to Predict Flap Thrombosis: A Systematic Review
Malapati H, Hanwright PJ, Tuffaha SH
Plastic and reconstructive surgery. Global open. 2021;9(8):e3769
Abstract
BACKGROUND Flap thrombosis is a rare but devastating complication in microsurgery. Preoperative identification of patients at increased risk for microvascular thrombosis remains challenging. Viscoelastic testing (VET) provides a comprehensive evaluation of the clotting process and can effectively identify hypercoagulability. However, the utility of VET in microvascular reconstruction remains unclear. METHODS A systematic review of the association between VET and pedicle thrombosis and free flap loss was performed in accordance with Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines. Identified studies were reviewed independently by two authors for pertinent data. RESULTS Six studies met inclusion criteria. Heterogenous study design and outcome reporting complicated direct comparisons and precluded a formal meta-analysis. Four studies found a statistically significant relationship between VET results and flap thrombosis or flap loss. The maximum clot strength and the fibrinogen-to-platelet ratio (FPR) were key viscoelastic parameters in these studies, both representing a measure of maximal clot strength. Specifically, an elevated FPR (>42%) generated a sensitivity and specificity for flap loss ranging from 57% to 75% and 60% to 82%, respectively. Notably, the negative predictive value for flap failure with a normal preoperative FPR was greater than 90% in all studies reporting a correlation. The remaining two studies reported no predictive value for VET with respect to flap failure or pedicle thrombosis. CONCLUSION The results of this review suggest that VET, particularly parameters relating to clot strength, may help clinicians identify patients at risk for flap thrombosis. However, uncontrolled and heterogenous reporting limit definitive conclusions, and high-quality diagnostic studies are needed to better determine the clinical utility of viscoelastic testing for free flap patients.
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Systematic Review and Meta-Analysis of Diagnostic Test Accuracy Studies Evaluating Point-of-Care Tests of Coagulopathy in Cardiac Surgery
Woźniak, M. J., Abbasciano, R., Monaghan, A., Lai, F. Y., Corazzari, C., Tutino, C., Kumar, T., Whiting, P., Murphy, G. J.
Transfusion Medicine Reviews. 2021;35(1):7-15
Abstract
Treatment guidelines recommend the routine use of point-of-care diagnostic tests for coagulopathy in the management of cardiac surgery patients at risk of severe bleeding despite uncertainty as to their diagnostic accuracy. We performed a systematic review and meta-analysis of studies that evaluated the diagnostic accuracy of viscoelastometry, platelet function tests, and modified thromboelastography (TEG) tests, for coagulopathy in cardiac surgery patients. The reference standard included resternotomy for bleeding, transfusion of non-red cell components, or massive transfusion. We searched MEDLINE, EMBASE, CINAHL, and Clinical Trials.gov, from inception to June 2019. Study quality was assessed using QUADAS-2. Bivariate models were used to estimate summary sensitivity and specificity with (95% confidence intervals). All 29 studies (7440 participants) included in the data synthesis evaluated the tests as predictors of bleeding. No study evaluated their role in the management of bleeding. None was at low risk of bias. Four were judged as low concern regarding applicability. Pooled estimates of diagnostic accuracy were; Viscoelastic tests, 12 studies, sensitivity 0.61 (0.44, 0.76), specificity 0.83 (0.70, 0.91) with significant heterogeneity. Platelet function tests, 12 studies, sensitivity 0.63 (0.53, 0.72), specificity 0.75 (0.64, 0.84) with significant heterogeneity. TEG modification tests, 3 studies, sensitivity 0.80 (0.67, 0.89), specificity 0.76 (0.69, 0.82) with no evidence of heterogeneity. Studies reporting the highest values for sensitivity and specificity had important methodological limitations. In conclusion, we did not demonstrate predictive accuracy for commonly used point-of-care devices for coagulopathic bleeding in cardiac surgery. However, the certainty of the evidence was low.
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A Systematic Review of Thromboelastography Utilization in Vascular and Endovascular Surgery
Kim Y, Patel SS, McElroy IE, DeCarlo C, Bellomo TR, Majumdar M, Lella SK, Mohebali J, Dua A
Journal of vascular surgery. 2021
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Editor's Choice
Abstract
OBJECTIVE Thromboelastography (TEG) is diagnostic modality that analyzes real-time blood coagulation parameters. Clinically, TEG primarily allows for directed blood component resuscitation among patients with acute blood loss and coagulopathy. The utilization of TEG has been widely adopted in among other surgical specialties; however, its use in vascular surgery is less prominent. We aimed to provide an up-to-date review of TEG utilization in vascular and endovascular surgery. METHODS Using PRISMA guidelines, a literature review with the Medical Subject Headings (MeSH) terms "TEG and arterial events", "TEG and vascular surgery", "TEG and vascular", "TEG and endovascular surgery", "TEG and endovascular", "TEG and peripheral artery disease", "TEG and prediction of arterial events", "TEG and prediction of complications ", "TEG and prediction of thrombosis", "TEG and prediction of amputation", and "TEG and amputation" was performed in Cochrane and PubMed databases to identify all peer-reviewed studies of TEG utilization in vascular surgery, written between 2000-2021 in the English language. The free text and MeSH subheadings search terms included diagnosis, complications, physiopathology, surgery, mortality, and therapy to further restrict the articles. Studies were excluded if they were not in humans or pertaining to vascular or endovascular surgery. Additionally, case reports and studies with limited information regarding TEG utilization were excluded. Each study was independently reviewed by two researchers to assess for eligibility. RESULTS Of the 262 studies identified through the MeSH strategy, 15 studies met inclusion criteria and were reviewed and summarized. Literature on TEG utilization in vascular surgery spanned cerebrovascular disease (n=3), peripheral arterial disease (n=3), arteriovenous malformations (n=1), venous thromboembolic events (n=7), and perioperative bleeding and transfusion (n=1). In cerebrovascular disease, TEG may predict the presence and stability of carotid plaques, analyze platelet function before carotid stenting, and compare efficacy of antiplatelet therapy after stent deployment. In peripheral arterial disease, TEG has been used to predict disease severity and analyze the impact of contrast on coagulation parameters. In venous disease, TEG may predict hypercoagulability and thromboembolic events among various patient populations. Finally, TEG can be utilized in the postoperative setting to predict hemorrhage and transfusion requirements. CONCLUSIONS This systematic review provides an up-to-date summarization of TEG utilization in multiple facets of vascular and endovascular surgery.
PICO Summary
Population
Patients undergoing vascular and endovascular surgery (15 studies).
Intervention
Systematic review to provide an up-to-date summarization of thromboelastography (TEG).
Comparison
Outcome
Literature on TEG utilization in vascular surgery spanned cerebrovascular disease (n=3), peripheral arterial disease (n=3), arteriovenous malformations (n=1), venous thromboembolic events (n=7), and perioperative bleeding and transfusion (n=1). In cerebrovascular disease, TEG may predict the presence and stability of carotid plaques, analyse platelet function before carotid stenting, and compare efficacy of antiplatelet therapy after stent deployment. In peripheral arterial disease, TEG has been used to predict disease severity and analyse the impact of contrast on coagulation parameters. In venous disease, TEG may predict hypercoagulability and thromboembolic events among various patient populations.
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Viscoelastic Blood Tests Use in Adult Cardiac Surgery: Meta-Analysis, Meta-Regression, and Trial Sequential Analysis
Meco, M., Montisci, A., Giustiniano, E., Greco, M., Pappalardo, F., Mammana, L., Panisi, P., Roscitano, C., Cirri, S., Donatelli, F., et al
Journal of Cardiothoracic and Vascular Anesthesia. 2020;34(1):119-127
Abstract
OBJECTIVES Postoperative hemorrhage in cardiac surgery is a significant cause of morbidity and mortality. Standard laboratory tests fail as predictors for bleeding in the surgical setting. The use of viscoelastic (VE) hemostatic assays thromboelastography (TEG) and rotational thromboelastometry (ROTEM) could be an advantage in patients undergoing cardiac surgery. The objective of this meta-analysis was to analyze the effects (benefits and harms) of VE-guided transfusion practice in cardiac surgery patients. DESIGN A meta-analysis of randomized trials. SETTING For this study, PubMed, EMBASE, Scopus, and the Cochrane Collaboration database were searched, and only randomized controlled trials were included. A systematic review and meta-analysis were performed in accordance with the standards set forth by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, using a random-effects model. PARTICIPANTS The study comprised adult cardiac surgery patients. INTERVENTIONS VE-hemostatic assays transfusion algorithm compared with transfusion algorithms based on clinicians' discretion. MEASUREMENTS AND MAIN RESULTS Seven comparative randomized controlled trials were considered, including a total of 1,035 patients (522 patients in whom a TEG- or ROTEM-based transfusion algorithm was used). In patients treated according to VE-guided algorithms, red blood cell (odds ratio 0.61; 95% confidence interval [CI]: 0.37-0.99; p: 0.04; I(2): 66%) and fresh frozen plasma transfusions (risk difference 0.22; 95% CI: 0.11-0.33; p < 0.0001; I(2): 79%) use was reduced; platelets transfusion was not reduced (odds ratio 0.61; 95% CI: 0.32-1.15; p: 0.12; I(2) 74%). CONCLUSIONS This study demonstrated that the use of VE assays in cardiac surgical patients is effective in reducing allogenic blood products exposure, postoperative bleeding at 12 and 24 hours after surgery, and the need for redo surgery unrelated to surgical bleeding.
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Use of Coagulation Point-of-Care Tests in the Management of Anticoagulation and Bleeding in Pediatric Cardiac Surgery: A Systematic Review
Bianchi P, Beccaris C, Norbert M, Dunlop B, Ranucci M
Anesth Analg. 2019
Abstract
Bleeding and coagulation management are essential aspects in the management of neonates and children undergoing cardiac surgery. The use of point-of-care tests (POCTs) in a pediatric setting is not as widely used as in the adult setting. This systematic review aims to summarize the evidence showed by the literature regarding the use of POCTs in children undergoing cardiac surgery. We included all studies examining the pediatric population (<18 years old) undergoing cardiac surgery in which the coagulation profile was assessed with POCTs. Three electronic databases (PubMed, Embase, and the Cochrane Controlled Clinical Trials register) were searched. Tests involved were heparin effect tests, viscoelastic tests, and platelet function tests. Due to the wide heterogeneity of the patients and tests studied, a formal meta-analysis was impossible, and the results are therefore presented through a systematic review. Eighty articles were found, of which 47 are presented in this review. At present, literature data are too weak to define POCTs as a "gold standard" for the treatment of perioperative bleeding in pediatric cardiac surgery. Nevertheless, introduction of POCTs into postoperative algorithms has shown to improve bleeding management, patient outcome, and cost efficiency.
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The Ability of Thromboelastography to Detect Hypercoagulability: A Systematic Review & Meta-Analysis
Wesley B, Matthew L, Michael M, Alexandra E, Christopher S, Richard J, Mara S
Journal of orthopaedic trauma. 2019
Abstract
OBJECTIVE We aimed to review the current literature on the use of viscoelastic hemolytic assays (VHA), like thromboelastography (TEG) and rotational thromboelastometry (ROTEM), during the perioperative period of patients and determine the ability of TEG and ROTEM to detect hypercoagulability and identify increased risk for the development of venous thromboembolism (VTE). DATA SOURCES PubMed, EMBASE, and Cochrane online databases were queried through February 11, 2018 by pairing the terms "thromboelastography," "viscoelastic hemostatic assays," and "rotational thromboelastometry" with "venous thromboembolism," "deep vein thrombosis," "pulmonary embolism," and "hypercoagulability." STUDY SELECTION Inclusion and exclusion criteria were established to determine relevance and quality of data, of which 2.54% of initially identified studies met. DATA EXTRACTION AND SYNTHESIS Articles and citations were reviewed for relevance by two independent individuals following PRISMA guidelines as well as a quality assessment of data as established by Zaza et. al. In studies that separated patients postoperatively by VTE development or no VTE development, data were pooled utilizing a modified DerSimmion and Laird random effects model. RESULTS 1,893 articles, were assessed for eligibility, yielding 370 abstracts. Of the 370 abstracts, 35 studies were included, and of these, only five were included in the meta-analysis. Studies included post-surgical patients in a variety of surgical fields, encompassing a total of 8,939 patients, with 717 thrombotic events reported. Elevated MA was a statistically significant indicator of hypercoagulability across at least one perioperative time point in 17 (50%) of the articles reviewed, consisting of 6,348 (72%) patients. The pooled mean MA value for defining hypercoagulability was greater than 66.70 mm. Using a pre-published value for hypercoagulability of 65mm, the combined effect of MA on the development of VTE in postsurgical patients was determined to be 1.31 (95% CI, .74-2.34, p=.175) and was 46% sensitive and 62% specific in predicting a postoperative VTE. CONCLUSION Only one parameter, MA, was consistently used to both define hypercoagulability and be predictive of VTE following traumatic injury and surgical intervention; however, there remains a broad variability in the definition of hypercoagulability as determined by MA and thus limits its predictive ability. Additionally, when hypercoagulability was measured throughout the perioperative period, TEG consistently demonstrated hypercoagulability starting on post-op day one (POD1).