Comparison between Endogenous Thrombin Potential (ETP) and INR To Assess Liver Function in Patients with Liver Cirrhosis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4015-4015
Author(s):  
Jeoffrey Schouten ◽  
Alain P. Gadisseur ◽  
Sven Franque ◽  
Marc Van der Planken ◽  
Peter Michielsen ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Liver Function ◽  
Liver Failure ◽  
Thrombin Generation ◽  
Coagulation Factors ◽  
Liver Function Tests ◽  
Prognostic Indicator ◽  
Classification Systems ◽  
Prognostic Models ◽  
Clear Correlation

Abstract The decreased hepatic synthesis of coagulation factors is a marker of liver failure and a prognostic indicator of survival in cirrhosis. The aPTT and PT/INR are the conventional coagulation tests to measure the haemostatic capacity of the liver. The INR was developed uniquely for use in patients under oral anticoagulation and may not adequately reflect the coagulation changes in liver cirrhosis. However, prognostic models for liver disease include the INR (MELD). New coagulation assessment tests are obviously needed in liver cirrhosis. Recently a test has become available to routinely measure the endogenous thrombin generation potential (ETP). This more physiological test is currently investigated in several haemostatic disorders but not yet in liver failure. The aim of the study is to investigate correlations between ETP performed on the BCS® system (both Dade Behring, Marburg, Germany) and liver function tests, and compared with INR. We analysed 112 patients with liver cirrhosis (73 Child A, 21 Child B, 18 Child C) without known pre-existing coagulation abnormalities. In these patients ETP, APTT, PT/INR and S-cholinesterase were measured and an C14-Aminopyrine breathing test was performed. Both INR and ETP show good correlation with the Child score (P<0.01) as a whole. Looking at the Child score for bilirubin there is a clear correlation with the normalized ETP with 0.84 (CI95 0.81 - 0.88) for Child A, 0.74 (CI95 0.55 - 0.93) for Child B, and 0.67 (CI95 0.60 - 0.75) for Child C (p<0.01). For the presence of ascites there is a correlation with the ETP with 0.86 (CI95 0.82 - 0.89) for Child A, 0.71 (CI95 0.62 - 0.79) for Child B, and 0.69 (CI95 0.59 - 0.80) for Child C (p<0.01). Looking at the albumin level there is a clear correlation with the normalized ETP with 0.83 (CI95 0.79 - 0.86) for Child A patients, 0.72 (CI95 0.57 - 0.88) for Child B, and 0.69 (CI95 0.60 - 0.78) for Child C (p=0.02). In a linear regression model bilirubin (β= −0.319, p<0.01) and ascites (β= −0.233, p=0.06) are the main predictive factor for decreasing thrombin generation. No such clear relationships can be identified for the INR. Both ETP and INR correlate well with S-cholinesterase levels (p<0.01). ETP correlated better with the breathing test than the INR. These results indicate that the integrity of the coagulation decreases in line with deterioration of other liver functions in patients with liver cirrhosis. The seriousness of this decrease in haemostatic capacity is better demonstrated by the ETP than by the INR (currently part of MELD). In the future the ETP may supersede the INR in prognostic classification systems for hepatic failure.

Liver Function Tests and Physiological Features of Liver Failure

2020 ◽  
pp. 241-242
Author(s):  
Peter Kam ◽  
Ian Power ◽  
Michael J. Cousins ◽  
Philip J. Siddal
Keyword(s):  
Liver Function ◽  
Liver Failure ◽  
Liver Function Tests ◽  
Function Tests

Rebalanced Thrombin Generation in Liver Cirrhosis Calls for Tailored Transfusion Protocols

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3523-3523 ◽  
Author(s):  
Romy Kremers ◽  
Marie-Claire Kleinegris ◽  
Hugo ten Cate ◽  
Bas De Laat ◽  
Rob Wagenvoord ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Prothrombin Time ◽  
In Silico ◽  
Healthy Subjects ◽  
Thrombin Generation ◽  
Prothrombin Complex Concentrate ◽  
Bleeding Risk ◽  
Coagulation Factors ◽  
Blood Product Transfusion ◽  
Cirrhosis Patient

Abstract Introduction Most coagulation factors are produced by the liver, and therefore in liver cirrhosis both pro- and anticoagulant factor levels are reduced. Cirrhosis patients show no clear systemic bleeding or thrombotic phenotype and thrombin generation (TG) is (almost) unaffected, therefore it has previously been proposed that coagulation is rebalanced in cirrhosis because both pro- and anticoagulant processes are affected to a similar extent. Nevertheless, clinical parameters such as the prothrombin time indicate a bleeding risk in cirrhosis patients, and based on these tests patients often receive blood product transfusion during surgery. In this study we investigated thrombin generation and its main underlying pro- and anticoagulant processes (prothrombin conversion and thrombin inactivation) to provide empirical evidence for the hypothesis of rebalanced thrombin generation in liver cirrhosis. In addition, we used in silico experimentation to study the consequences of rebalanced TG for current transfusion practices. Methods 25 cirrhosis patients and 25 healthy subjects were enrolled in our study. The group of cirrhosis patients consisted of 22 Child-Pugh A and 3 Child-Pugh B patients. Prothrombin, antithrombin (AT) and α2Macroglobulin (α2M) levels were determined and TG was measured at 5 pM tissue factor by calibrated automated thrombinography. Prothrombin conversion and thrombin inactivation were quantified from each TG curve, and thrombin-antithrombin and thrombin-α2Macroglobulin complex formation was determined. The effect of transfusion of prothrombin complex concentrate (PCC) was simulated by an in silico increase of prothrombin conversion. The increase of prothrombin conversion was simulated by substituting the prothrombin conversion curve of a cirrhosis patient by the average healthy subject prothrombin conversion curve, to normalize prothrombin conversion in patients. Thrombin generation curves were calculated based on this normalized prothrombin conversion curve and the original thrombin inactivation parameters of each cirrhosis patient. Results Prothrombin and antithrombin are significantly decreased in cirrhosis patients (74 % and 70 %, p<0.001), whereas the α2M level is significantly increased (p<0.001). Thrombin generation in healthy subjects and patients is similar (figure), although prothrombin conversion (65 %, p<0.001) and thrombin inactivation (73 % p<0.001) are markedly reduced in cirrhosis patients. Acquired AT deficiency results in a reduction of thrombin inactivation by AT (64 %, p<0.001), but the substitution of AT by α2M leads to increased thrombin inactivation by α2M (220 %, p<0.001). The effect of prothrombin complex concentrate transfusion on thrombin generation in cirrhosis patients was determined by computational modeling (figure). In silico normalization of prothrombin conversion, as would be achieved by PCC transfusion, causes TG to rise to levels that have been shown to be highly prothrombotic (ETP 2878 ± 1323 nM∙min, p<0.001). Conclusions Despite large differences in prothrombin conversion and thrombin inactivation, TG in liver cirrhosis patients remains within the normal range (rebalanced), in contrast to the prothrombin time that predicts a bleeding risk in these patients. The transfusion of PCC based on a prolonged prothrombin time would result in a substantial elevation of thrombin generation. This indicates that standard transfusion protocols need to be tailored to the specific needs of cirrhosis patients. Figure 1. Thrombin generation in healthy subjects (■), cirrhosis patients (●), and cirrhosis patients transfused with PCC (in silico; ○). ***p<0.001 Figure 1. Thrombin generation in healthy subjects (■), cirrhosis patients (●), and cirrhosis patients transfused with PCC (in silico; ○). ***p<0.001 Disclosures Kremers: Synapse bv: Employment. De Laat:Synapse bv: Employment. Wagenvoord:Synapse bv: Employment. Hemker:Synapse bv: Employment.

scholarly journals A Patient with Nafcillin-Associated Drug-Induced Liver Failure

2017 ◽  
Vol 11 (3) ◽  
pp. 564-568 ◽  
Author(s):  
Qin Rao ◽  
Isaiah Schuster ◽  
Talal Seoud ◽  
Kevin Zarrabi ◽  
Nirvani Goolsarran
Keyword(s):  
Liver Injury ◽  
Liver Function ◽  
Liver Failure ◽  
Acute Liver Injury ◽  
Early Recognition ◽  
Antibiotic Use ◽  
Liver Function Tests ◽  
The United States ◽  
Drug Induced ◽  
Drug Induced Liver Injury

Nafcillin-induced acute liver injury is a rare and potentially fatal complication that has been known since the 1960s but inadequately studied. At this time, the only proven treatment is early discontinuation of the drug. Because of the high prevalence of nafcillin class antibiotic use in the United States, it is important for clinicians to have a high clinical suspicion for this diagnosis. We present a case of liver failure attributable to nafcillin use in a 68-year-old male with a history methicillin-sensitive Staphylococcus and L3/L4 osteomyelitis. After starting long-term antibiotic therapy, he presented with painless jaundice which necessitated discontinuation of the drug. At the time of presentation, the patient’s lab work exhibited a bilirubin/direct bilirubin of 9.4/8.2 mg/dL, alkaline phosphatase of 311 IU/L, and aspartate transaminase/alanine transaminase of 109/127 IU/L. The patient was switched to i.v. vancomycin given the concern for drug-induced liver injury. Imaging did not show obstruction of the hepatobiliary or pancreaticobiliary trees. Serology was unremarkable for viral etiology, autoimmune processes, Wilson disease, and hemochromatosis. A liver biopsy showed findings consistent with drug-induced liver injury. The patient’s liver function tests peaked at day 7 of admission and trended towards normal levels with cessation of nafcillin therapy. The patient was discharged with a diagnosis of nafcillin-induced acute liver injury. Our case highlights the importance of early recognition of the diagnosis and careful monitoring of liver function when nafcillin is employed in the clinical setting.

Hepatic disorders

2011 ◽  
Author(s):  
Carl Waldmann ◽  
Neil Soni ◽  
Andrew Rhodes
Keyword(s):  
Hepatic Encephalopathy ◽  
Liver Function ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Serum Bilirubin ◽  
Liver Function Tests ◽  
Abnormal Liver Function ◽  
Chronic Liver ◽  
Bile Pigments ◽  
Chronic Liver Failure

Jaundice 348Acute liver failure 350Hepatic encephalopathy 352Chronic liver failure 354Abnormal liver function tests 356Jaundice (icterus) is the accumulation of bile pigments in serum and tissues including sclerae and skin. Jaundice is usually clinically detectable once serum bilirubin exceeds 50...

Routine Measurement of Endogenous Thrombin Potential (ETP) To Assess Hemostatic Function in Patients with Liver Cirrhosis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4014-4014
Author(s):  
Alain P. Gadisseur ◽  
Jeoffrey Schouten ◽  
Sven Franque ◽  
Marc Van der Planken ◽  
Peter Michielsen ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Thrombin Generation ◽  
Pearson Correlation ◽  
Area Under The Curve ◽  
Classification Systems ◽  
Bleeding Tendency ◽  
Endogenous Thrombin Potential ◽  
Automated Assay ◽  
The Mean

Abstract The maintenance of hemostasis through the production of most of the coagulation proteins is a basic liver function. In patients with cirrhosis of the liver the decrease in these proteins is one of the contributory factors to an increased bleeding tendency. Normally the hemostatic capacity of the liver is measured through routine clotting tests as the activated Partial Thromboplastin Time (aPTT) and Prothrombin Time (PT). In the Child classification for liver cirrhosis the coagulation as expressed by the PT is one of the determinants. Recently a test has become available which will make it possible to routinely measure the endogenous thrombin generation potential (ETP) which may be a better alternative. In this test according to the method first described by Hemker (1993) thrombin generation is continuously measured by use of a chromogenic substrate. Results are calculated as area under the curve and as a percentage of normal. We analysed 110 patients with liver cirrhosis classified according to the Child classification, 79 patients with stage A, 19 stage B and 12 stage C, without known pre-existing coagulation abnormalities like inherited bleeding disorders, or anticoagulant drugs. In these patients ETP, APTT, PT/INR, FV, FVII and FXI were measured. We used a fully automated assay for the determination of the endogenous thrombin potential (ETP) on the BCS® System (both Dade Behring, Marburg, Germany). The results for the mean PT were 81% (CI95 77 - 85) for Child A patients, 53% (CI95 44 - 63) for Child B, and 41% (CI95 33 - 50) for Child C. For the mean INR the results were 1.11 (CI95 1.08 - 1.14) for Child A patients, 1.65 (CI95 1.22 - 2.08) for Child B, and 1.82 (CI95 1.34 - 2.31) for Child C. The results for the mean normalized ETP were 0.87 (CI95 0.84 - 0.90) for Child A patients, 0.78 (CI95 0.68 - 0.88) for Child B, and 0.58 (CI95 0.51 - 0.64) for Child C (p&lt;0.001). While the normalized ETP correlated well with both PT and INR for Child B (P&lt;0.05) and C (p&lt;0.01), there were significant differences within the child A patients where no significant correlation could be identified (Pearson correlation 0.203, R2=0.04, p=0.075. We conclude that the fully automated assay for the determination of the endogenous thrombin potential (ETP) on the BCS® System (both Dade Behring, Marburg, Germany) is a potentially interesting test to measure the coagulation abilities in patients with liver cirrhosis which in the future may supersede the PT/INR in classification systems for hepatic disease.

scholarly journals A CASE REPORT ON ROLE OF N-ACETYLCYSTEINE IN NON–ACETAMINOPHEN RELATED ACUTE LIVER INJURY

2016 ◽  
Vol 9 (6) ◽  
pp. 7
Author(s):  
Anooja Thampi
Keyword(s):  
Liver Injury ◽  
Liver Function ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Acute Liver Injury ◽  
Liver Function Tests ◽  
Function Test ◽  
Cytosolic Glutathione ◽  
Antioxidant Agent

 Acute liver failure is a clinical entity associated with a high mortality rate and majority of these patients may require liver transplantation. N-Acetylcysteine (NAC), an antioxidant agent that replenishes mitochondrial and cytosolic glutathione stores, is an antidote for acetaminophen poisoning. But their role in non–acetaminophen-related acute liver failure is still not proven. Here, we discuss about a 67 year old male patient diagnosed with hepatitis with acute liver injury who was admitted in Emergency Medicine. He was treated with N- Acetylcysteine infusion for an average of 48 hours and later it was found that his liver function tests improved. In this study, we could find that N-Acetylcysteine plays a major role in improving the liver function test of patients with non–acetaminophen-related acute liver failure.

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