Coagulation in acutely ill patients with severe chronic liver disease: Insights from thromboelastography

Lloyd-Donald, Patryck; Vasudevan, Abhinav; Angus, Peter W; Gow, Paul J; Mårtensson, Johan; Glassford, Neil J; Eastwood, Glenn M; Hart, Graeme K; Bellomo, Rinaldo

doi:10.1016/j.jcrc.2016.10.030

Cited by 32 publications

(32 citation statements)

References 33 publications

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“…Patients with de novo sepsis demonstrated the lowest protein C and AT‐III levels, and the highest vWF and Factor VIII levels at days 3 and 7 across all three groups possibly due to the severity of hepatic dysfunction, sepsis and multiple antibiotic usages causing myelosuppression . Prophylactic antibiotic therapy has led to less early rebleeding and better control of variceal bleeding .…”

Section: Discussionmentioning

confidence: 99%

“…Patients with de novo sepsis demonstrated the lowest protein C and AT-III levels, and the highest vWF and Factor VIII levels at days 3 and 7 across all three groups possibly due to the severity of hepatic dysfunction, sepsis and multiple antibiotic usages causing myelosuppression. 30 Prophylactic antibiotic therapy has led to less early rebleeding and better control of variceal bleeding. 31 Fisher et al compared the coagulation profile in patients with ACLF (n = 17), AD of cirrhosis (n = 44) and stable cirrhotics (n = 8) and found that there was a progressive increase in INR, Factor VIII and vWF levels and a corresponding decrease in antithrombin, ADAMTS-13 and fibrinogen levels.…”

Section: Coagulation Profile Changes In Aclf With Sepsismentioning

confidence: 99%

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Coagulation failure is associated with bleeding events and clinical outcome during systemic inflammatory response and sepsis in acute‐on‐chronic liver failure: An observational cohort study

Premkumar

Saxena

Rangegowda

et al. 2019

Liver International

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Background Patients with acute‐on‐chronic liver failure (ACLF) have coagulation failure in the setting of systemic inflammatory syndrome (SIRS), sepsis and extra‐hepatic organ failures. Methods Consecutive ACLF patients without sepsis at baseline were assessed at days 0, 3 and 7 with thromboelastography (TEG) and specific assays (Factor VIII, von Willebrand factor [vWF], protein C and antithrombin III [ATIII]) and followed for development of sepsis, bleeding and outcome. Results Of 243 patients, 114 (63% ethanol related; mean age 44.3 ± 11.7 years; 90% male) were recruited. SIRS was noted in 39 (34.2%), 45 (39.5%) and 46 (40%) patients at days 0, 3 and 7 and sepsis in 28 (24%) and 52 (56.1%) patients at days 3 and 7 respectively. The 28‐ and 90‐day survivals were 62% and 51% respectively. A hypocoagulable TEG at baseline was a predictor of bleeding (hazard ratio [HR] 2.1; CI 1.6‐4.9; P = 0.050) and mortality (HR 1.9; CI 1.3‐7.9; P = 0.043). ACLF patients had increased Factor VIII, vWF, tissue factor levels and tissue plasminogen activator (tPA) activity with reduced protein C and ATIII. Coagulation parameters like Coagulation Index (HR 2.1; CI 1.1‐4.5; P = 0.044),clot lysis (HR 3.2; CI 1.9‐3.4; P = 0.033), low protein C < 30% (HR 2.1; CI 1.5‐2.8; P = 0.017), ATIII (HR 1.4; CI 1.7‐3.1; P = 0.052) and tPA (HR 1.5; CI 1.1‐2.4; P = 0.052) were predictors of mortality at day 28. Protein C activity <30% (HR 1.3; CI 1.0‐2.9; P = 0.042) and tPA >20 ng/mL (HR 1.2; CI 1.1‐2.1; P = 0.040) predicted mortality when adjusted for age, gender and baseline MELD. Conclusions Dynamic coagulation derangements, measured by TEG, determine the likelihood of bleeding and mortality in ACLF.

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Section: Discussionmentioning

confidence: 99%

Section: Coagulation Profile Changes In Aclf With Sepsismentioning

confidence: 99%

Coagulation failure is associated with bleeding events and clinical outcome during systemic inflammatory response and sepsis in acute‐on‐chronic liver failure: An observational cohort study

Premkumar

Saxena

Rangegowda

et al. 2019

Liver International

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“…The study reported delayed clot formation and decreased clot strength in the TE test associated with increased severity of cirrhosis and no alterations in clot degradation. Similar results were reported recently by Lloyd‐Donald et al in a study that included 34 patients with advanced cirrhosis evaluated by thromboelastography (TEG). TEG measurements showed hypocoagulable features with delayed clot formation and decreased MCF.…”

Section: Discussionmentioning

confidence: 99%

Coagulation Failure in Patients With Acute‐on‐Chronic Liver Failure and Decompensated Cirrhosis: Beyond the International Normalized Ratio

et al. 2018

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Balanced hemostasis with hypocoagulable and hypercoagulable features may occur in acute-on-chronic liver failure (ACLF). The characteristics and prognostic impact of the coagulation profile in ACLF are unknown. Consecutive patients with ACLF (n = 36) and acute decompensation (AD; n = 24) were included. Blood samples for thromboelastometry (TE) were obtained at admission and 72 hours thereafter. The coagulation profile was evaluated in patients with and without ACLF and in those with and without systemic inflammatory response syndrome. The impact of the coagulation profile on transfusion requirements, bleeding events, and short-term survival was assessed. At admission, patients with ACLF showed more hypocoagulable characteristics compared to AD subjects, with prolonged time to initial fibrin formation and clot formation time and decreased maximum clot firmness and alpha-angle values. TE parameters worsened at 72 hours in ACLF but improved in patients with AD. Prevalence of a hypocoagulable profile (three or more TE parameters outside range) was significantly higher in patients with ACLF either at admission (61% versus 29% in AD; P = 0.03) or during follow-up. Hypocoagulability correlated with systemic inflammation and was associated with higher 28-day (45% versus 16%; P = 0.02) and 90-day (52% versus 19%; P = 0.01) mortality rates but not with transfusion requirements or bleeding. Prolonged time to initial fibrin formation (extrinsic TE assay >80 seconds) and Model for End-Stage Liver Disease score at baseline were independent predictors of 28-day mortality. Conclusion: Patients with ACLF frequently show hypocoagulable features with prolonged time to initial fibrin formation and clot formation time and reduced clot firmness; these alterations worsen after admission, correlate with systemic inflammation, and translate into higher short-term mortality; hypofibrinolysis could contribute to organ failure in ACLF.

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“…TEG is a point‐of‐care, global hemostasis assessment device that measures the viscoelastic changes that occur during the hemostatic process, providing real‐time reports. TEG is often normal in patients with compensated cirrhosis and can display hypocoagulable features in patients with advanced cirrhosis …”

mentioning

confidence: 99%

“…TEG is often normal in patients with compensated cirrhosis (3,4) and can display hypocoagulable features in patients with advanced cirrhosis. (5,6) TEG is considered to be a more reliable test to assess coagulation than traditional tests (INR, PLTs) to guide transfusions in patients undergoing cardiac, trauma, and abdominal surgery and liver transplantation, and in patients with cirrhosis and significant coagulopathy undergoing invasive procedures. (7)(8)(9)(10)(11)(12)(13)(14)(15) A recently published systematic review and metaanalysis assessed the randomized controlled trials performed on patients in acute need of blood transfusions due to bleeding (not limited to liver disease patients), to evaluate the effect of VHA guidance on bleeding, transfusion requirements, and mortality.…”

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confidence: 99%

Thromboelastography‐Guided Blood Component Use in Patients With Cirrhosis With Nonvariceal Bleeding: A Randomized Controlled Trial

et al. 2019

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Thromboelastography (TEG) provides a more comprehensive global coagulation assessment than routine tests (international normalized ratio [INR] and platelet [PLT] count), and its use may avoid unnecessary blood component transfusion in patients with advanced cirrhosis and significant coagulopathy who have nonvariceal upper gastrointestinal (GI) bleeding. A total of 96 patients with significant coagulopathy (defined in this study as INR >1.8 and/or PLT count < 50 × 109/L) and nonvariceal upper GI bleed (diagnosed after doing upper gastrointestinal endoscopy, which showed ongoing bleed from a nonvariceal source) were randomly allocated to TEG‐guided transfusion strategy (TEG group; n = 49) or standard‐of‐care (SOC) group (n = 47). In the TEG group, only 26.5% patients were transfused with all three blood components (fresh frozen plasma [FFP], PLTs, and cryoprecipitate) versus 87.2% in the SOC group (P < 0.001). Although 7 (14.3%) patients in the TEG group received no blood component transfusion, there were no such patients in the SOC group (P = 0.012). Also, there was a significantly lower use of blood components (FFP, PLTs, and cryoprecipitate) in the TEG group compared with the SOC group. Failure to control bleed, failure to prevent rebleeds, and mortality between the two groups were similar. Conclusion: In patients with advanced cirrhosis with coagulopathy and nonvariceal upper GI bleeding, TEG‐guided transfusion strategy leads to a significantly lower use of blood components compared with SOC (transfusion guided by INR and PLT count), without an increase in failure to control bleed, failure to prevent rebleed, and mortality.

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Coagulation in acutely ill patients with severe chronic liver disease: Insights from thromboelastography

Cited by 32 publications

References 33 publications

Coagulation failure is associated with bleeding events and clinical outcome during systemic inflammatory response and sepsis in acute‐on‐chronic liver failure: An observational cohort study

Coagulation failure is associated with bleeding events and clinical outcome during systemic inflammatory response and sepsis in acute‐on‐chronic liver failure: An observational cohort study

Coagulation Failure in Patients With Acute‐on‐Chronic Liver Failure and Decompensated Cirrhosis: Beyond the International Normalized Ratio

Thromboelastography‐Guided Blood Component Use in Patients With Cirrhosis With Nonvariceal Bleeding: A Randomized Controlled Trial

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