Thromboelastography-Guided Therapy Enhances Patient Blood Management in Cirrhotic Patients: A Meta-analysis Based on Randomized Controlled Trials
Hartmann J, Dias JD, Pivalizza EG, Garcia-Tsao G
Seminars in thrombosis and hemostasis. 2022
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Patients with cirrhosis often have abnormal hemostasis, with increased risk of hemorrhage and thrombosis. Thromboelastography provides a rapid assessment of the coagulation status and can guide product transfusions in adult patients with cirrhosis. This study aimed to determine whether the use of thromboelastography in adult patients with cirrhosis decreases blood product use and impacts adverse events or mortality compared with standard practice. A registered (PROSPERO CRD42020192458) systematic review and meta-analysis was conducted for randomized controlled trials (RCTs) comparing thromboelastography-guided hemostatic management versus standard practice (control). Co-primary outcomes were the number of transfused platelet units and fresh frozen plasma (FFP) units. Secondary outcomes were mortality, adverse events, utilization of individual blood products, blood loss or excessive bleeding events, hospital/intensive care unit stay, and liver transplant/intervention outcomes. The search identified 260 articles, with five RCTs included in the meta-analysis. Platelet use was five times lower with thromboelastography versus the control, with a relative risk of 0.17 (95% confidence interval [CI]: [0.03-0.90]; p = 0.04), but FFP use did not differ significantly. Thromboelastography was associated with less blood product (p < 0.001), FFP + platelets (p < 0.001), and cryoprecipitate (p < 0.001) use. No differences were reported in bleeding rates or longer term mortality between groups, with the thromboelastography group having lower mortality at 7 days versus the control (relative risk [95% CI] = 0.52 [0.30-0.91]; p = 0.02). Thromboelastography-guided therapy in patients with cirrhosis enhances patient blood management by reducing use of blood products without increasing complications.
Patients with cirrhosis (5 studies, n= 302).
Thromboelastography-guided haemostatic management.
Standard coagulation testing (standard practice).
Platelet use was five times lower with thromboelastography vs. standard practice, with a relative risk of 0.17 (95% confidence interval [CI]: [0.03-0.90]), but fresh frozen plasma (FFP) use did not differ significantly. Thromboelastography was associated with less blood product, FFP + platelets, and cryoprecipitate use. No differences were reported in bleeding rates or longer-term mortality between groups, with the thromboelastography group having lower mortality at 7 days vs. standard practice (relative risk [95% CI] = 0.52 [0.30-0.91]).
Viscoelastic Testing Prior to Non-surgical Procedures Reduces Blood Product Use Without Increasing Bleeding Risk in Cirrhosis
Shenoy, A., Louissaint, J., Shannon, C., Tapper, E. B., Lok, A. S.
Digestive Diseases and Sciences. 2022;67(11):5290-5299
BACKGROUND/AIMS: Thromboelastography (TEG) and Rotational Thromboelastometry (ROTEM) analyze hemostatic function in patients with coagulopathy. We sought to quantify the impact of TEG and ROTEM-guided transfusion algorithms on blood product utilization in patients with cirrhosis undergoing non-surgical procedures. METHODS We performed a systematic review and meta-analysis on the utility of viscoelastic testing prior to non-surgical procedures to determine their impact on pre-procedural blood product use and post-procedural bleeding events. Studies comparing TEG or ROTEM-guided transfusions with standard-of-care (SOC) prior to non-surgical procedures in adult patients with cirrhosis were included. Primary outcomes were fresh frozen plasma (FFP) and platelet transfusion and secondary outcomes of post-procedure bleeding, transfusion-related complications, and mortality; and were reported as standardized mean differences (SMD) and risk ratios (RR). RESULTS Six studies (five randomized controlled trials and one cohort study) involving 367 patients met inclusion criteria. Compared with SOC, TEG/ROTEM-guided transfusions led to an overall decreased number of patients who received FFP transfusions (SMD = -0.93, 95% CI [-1.54, -0.33], p < 0.001) and platelets transfusions (SMD = -1.50, CI [-1.85, -1.15], p < 0.001). Total amount of FFP (SMD-0.86, p < 0.001) and platelet (SMD = -0.99, p < 0.001) transfused in the TEG/ROTEM group were also lower. Decreased pre-procedure transfusion in the TEG/ROTEM group did not result in increased post-procedure bleeding (RR = 0.61, p = 0.09) or in mortality (RR = 0.91, p = 0.93). CONCLUSION In patients with cirrhosis, TEG or ROTEM significantly reduces blood product utilization prior to non-surgical procedures, with no increase in post-procedure bleeding or mortality. TEG and ROTEM utilization can promote high-value care and improve transfusion stewardship in this population.
Systematic review and meta-analysis: incidence of variceal hemorrhage in patients with cirrhosis undergoing transesophageal echocardiography
Odewole M, Sen A, Okoruwa E, Lieber SR, Cotter TG, Nguyen AD, Mufti A, Singal AG, Rich NE
Alimentary pharmacology & therapeutics. 2022
BACKGROUND The presence of esophageal varices is considered a relative contraindication to transesophageal echocardiography (TEE) by cardiology professional societies, so gastroenterologists are often consulted to perform upper endoscopy prior to TEE in patients with cirrhosis. AIM: To perform a systematic review to quantify the risk of bleeding complications in patients with cirrhosis following TEE. METHODS Two reviewers searched Ovid MEDLINE, MEDLINE In-Process and EMBASE databases from January 1992 to May 2021 for studies reporting bleeding complications from TEE in patients with cirrhosis. We calculated the pooled incidence rate of bleeding events using the metaprop command with a random effect model. RESULTS We identified 21 studies comprising 4050 unique patients with cirrhosis; 9 studies (n = 3015) assessed the risk of intraoperative TEE during liver transplant (LT) and 12 studies (n = 1035) assessed bleeding risk in patients undergoing TEE for other indications. The pooled incidence of bleeding post-TEE was 0.37% (95% CI 0.04-0.94%) across all studies. Bleeding complications were low among patients undergoing TEE during LT as well as those undergoing TEE for other diagnostic reasons (0.97% vs. 0.004%) and among studies with mean MELD >18 compared to those with mean MELD <18 (0.43% vs. 0.08%). Few studies had a comparator arm, and data on patient-level factors impacting bleeding complications (including degree of liver dysfunction and coagulopathy) were limited across studies. CONCLUSIONS The risk of bleeding complications following TEE is low in patients with cirrhosis, suggesting TEE is safe and risk stratification with upper endoscopy may not be necessary.
Primary prevention of bleeding from esophageal varices in patients with liver cirrhosis: An update and review of the literature
Garbuzenko DV, Arefyev NO
Journal of evidence-based medicine. 2020
All patients with liver cirrhosis and portal hypertension should be stratified by risk groups to individualize different therapeutic strategies to increase the effectiveness of treatment. In this regard, the development of primary prophylaxis of variceal bleeding and its management according to the severity of portal hypertension may be promising. This paper is to describe the modern principles of primary prophylaxis of esophageal variceal bleeding in patients with liver cirrhosis. The PubMed and EMbase databases, Web of Science, Google Scholar, and the Cochrane Database of Systematic Reviews were used to search for relevant publications from 1999 to 2019. The results suggested that depending on the severity of portal hypertension, patients with cirrhosis should be divided into those who need preprimary prophylaxis, which aims to prevent the formation of esophageal varices, and those who require measures that aim to prevent esophageal variceal bleeding. In subclinical portal hypertension, therapy should be etiological and pathogenetic. Cirrhosis with clinically significant portal hypertension should receive nonselective β-blockers if they have small esophageal varices and risk factors for variceal bleeding. Nonselective β-blockers are the first-line drugs for the primary prevention of bleeding from medium to large-sized esophageal varices. Endoscopic band ligation is indicated for the patients who are intolerant to nonselective β-blockers or in the case of contraindications to pharmacological therapy. In summary, the stratification of cirrhotic patients by the severity of portal hypertension and an individual approach to the choice of treatment may increase the effectiveness of therapy as well as improve survival rate of these patients.
Clinical utility of viscoelastic testing in chronic liver disease: A systematic review
Wei, H., Child, L. J.
World Journal of Hepatology. 2020;12(11):1115-1127
BACKGROUND Conventional coagulation tests are widely used in chronic liver disease to assess haemostasis and to guide blood product transfusion. This is despite the fact that conventional tests do not reliably separate those with a clinically significant coagulopathy from those who do not. Viscoelastic testing such as thromboelastography (TEG) correlate with bleeding risk and are more accurate in identifying those who will benefit from blood product transfusion. Despite this, viscoelastic tests have not been widely used in patients with chronic liver disease outside the transplant setting. AIM: To assess the utility of Viscoelastic Testing guided transfusion in chronic liver disease patients presenting with bleeding or who require an invasive procedure. METHODS PubMed and Google Scholar searches were performed using the key words "thromboelastography", "TEG" or "viscoelastic" and "liver transplantation", "cirrhosis" or "liver disease" and "transfusion", "haemostasis", "blood management" or "haemorrhage". A full text review was undertaken and data was extracted from randomised control trials that evaluated the outcomes of viscoelastic test guided transfusion in those with liver disease. The study subjects, inclusion and exclusion criteria, methods, outcomes and length of follow up were examined. Data was extracted by two independent individuals using a standardized collection form. The risk of bias was assessed in the included studies. RESULTS A total of five randomised control trials included in the analysis examined the use of TEG guided blood product transfusion in cirrhosis prior to invasive procedures (n = 118), non-variceal haemorrhage (n = 96), variceal haemorrhage (n = 60) and liver transplantation (n = 28). TEG guided transfusion was effective in all five studies with a statistically significant reduction in overall blood product transfusion compared to standard of care. Four of the five studies reported a significant reduction in transfusion of fresh frozen plasma and platelets. Two studies showed a significant reduction in cryoprecipitate transfusion. No increased risk of bleeding was reported in the three trials where TEG was used perioperatively or prior to an invasive procedure. Two trials in the setting of cirrhotic variceal and non-variceal bleeding showed no difference in control of initial bleeding. In those with variceal bleeding, there was a statistically significant reduction in rate of re-bleeding at 42 d in the TEG arm 10% (vs 26.7% in the standard of care arm P = 0.012). Mortality data reported at various time points for all five trials from 6 wk up to 3 years was not statistically different between each arm. One trial in the setting of non-variceal bleeding demonstrated a significant reduction in adverse transfusion events in the TEG arm 30.6% (vs 74.5% in the control arm P < 0.01). In this study there was no significant difference in total hospital stay although length of stay in intensive care unit was reduced by an average of 2 d in the TEG arm (P = 0.012). CONCLUSION Viscoelastic testing has been shown to reduce blood product usage in chronic liver disease without compromising safety and may enable guidelines to be developed to ensure patients with liver disease are optimally managed.
Systematic review with meta-analysis: abnormalities in the international normalised ratio do not correlate with periprocedural bleeding events among patients with cirrhosis
Kovalic AJ, Majeed CN, Samji NS, Thuluvath PJ, Satapathy SK
Alimentary pharmacology & therapeutics. 2020;52(8):1298-1310
BACKGROUND Cirrhotic coagulopathy is a delicate interplay comprising deficiencies of both procoagulant and anticoagulant factors. AIM: To identify the relationship between international normalised ratio [INR] with periprocedural bleeding risk among patients with cirrhosis. METHODS Following a thorough database search of the primary literature, 29 studies were targeted for analysis, including 13 276 patients with cirrhosis undergoing indicated procedures. RESULTS There was no significant association between periprocedural bleeding events and pre-procedural INR [pooled odds ratio 1.52; 95% CI 0.99, 2.33; P = 0.06]. Furthermore, there was no significant difference in mean INR [pooled mean difference 0.05; 95% CI -0.03, 0.13; P = 0.23] upon comparison of patients who either did or did not experience a periprocedural bleeding event. Significant heterogeneity among some studies was primarily fuelled by significant subgroup effects of both specific procedure types performed. Additionally, there were markedly inconsistent transfusion practices across studies. CONCLUSIONS INR fails to serve as a significant correlate for periprocedural bleeding events among patients with cirrhosis. Ideally, these new findings will help serve as a springboard for future studies, as well as to minimize transfusion of blood products, which command a myriad of adverse effects among patients with cirrhosis.
Thromboelastography versus standard coagulation testing in the assessment and reversal of coagulopathy among cirrhotics: a systematic review and meta-analysis
Kovalic AJ, Khan MA, Malaver D, Whitson MJ, Teperman LW, Bernstein DE, Singal A, Satapathy SK
European journal of gastroenterology & hepatology. 2020;32(3):291-302
The utility of thromboelastography/thromboelastometry currently has unvalidated clinical benefit in the assessment and reversal of coagulopathy among cirrhotic patients as compared to standard coagulation testing. A novel systematic review and meta-analysis was conducted in order to assess pooled outcome data among patients receiving thromboelastography/thromboelastometry as compared to standard coagulation testing. As compared to standard coagulation testing, there was a significant reduction in the number of patients requiring pRBC, platelet, and fresh frozen plasma transfusions among thromboelastography/thromboelastometry group with pooled OR 0.53 (95% CI 0.32-0.85; P = 0.009), 0.29 (95% CI 0.12-0.74; P = 0.009), and 0.19 (95% CI 0.12-0.31; P < 0.00001), respectively. Similarly, there was a significant reduction in number of pRBC, platelet, and fresh frozen plasma units transfused in the thromboelastography/thromboelastometry group with pooled MD -1.53 (95% CI -2.86 to -0.21; P = 0.02), -0.57 (95% CI -1.06 to -0.09; P = 0.02), and -2.71 (95% CI -4.34 to -1.07; P = 0.001), respectively. There were significantly decreased total bleeding events with pooled OR 0.54 (95% CI 0.31-0.94; P = 0.03) and amount of intraoperative bleeding during liver transplantation with pooled MD -1.46 (95% CI -2.49 to -0.44; P = 0.005) in the thromboelastography/thromboelastometry group. Overall, there was no significant difference in mortality between groups with pooled OR 0.91 (95% CI 0.63-1.30; P = 0.60). As compared to standard coagulation testing, a thromboelastography/thromboelastometry-guided approach to the assessment and reversal of cirrhotic coagulopathy improves overall number of patients exposed to blood product transfusions, quantity of transfusions, and bleeding events.