Coagulopathy, Bleeding Events, and Outcome According to Rotational Thromboelastometry in Patients With Acute Liver Injury/Failure
Open accessAbstract
Background and Aims: Patients with acute liver injury or failure (ALI/ALF) experience bleeding complications uncommonly despite an abnormal hemostatic profile. Rotational thromboelastometry (ROTEM), which assesses clot formation in whole blood, was used to determine the nature of abnormal hemostasis and whether it contributes to bleeding events, illness severity, or survival. Approach and Results: A total of 200 patients were recruited from sites of the ALF Study Group. Blood collected daily for up to 5 days was analyzed using ROTEM delta devices. Consistent with standard laboratory evidence of hypocoagulability (median international normalized ratio = 2.9 and platelet count = 144 × 10 9/L), patients frequently exhibited ROTEM parameters outside the normal range (73% and 62% had abnormalities in clot formation from extrinsic and intrinsic clotting cascades, respectively); however, measures of clot stability were generally normal. Eighteen patients (9%) experienced bleeding events, in whom clot initiation, assembly, and firmness were more severely deranged than patients without bleeding. Abnormal ROTEM parameters were more frequently observed in patients with non‐acetaminophen ALI/ALF than those with acetaminophen ALI/ALF (clot initiation [P < 0.001], assembly [P = 0.02], firmness at 10 minutes [P = 0.05], and maximal firmness [P = 0.06]). Patients with more severe systemic complications (high‐grade hepatic encephalopathy and need for renal replacement therapy) also had a higher incidence of abnormal ROTEM parameters. Finally, more hypocoagulable ROTEM parameters (clot initiation (P = 0.005), stiffness at 10 minutes (P = 0.05), and maximal stiffness by fibrin assembly (P = 0.004)) were observed in patients who died or underwent liver transplantation than those who survived with their native liver. Conclusions: In patients with ALI/ALF, abnormal ROTEM parameters are frequent and proportional to disease severity. Whether the increased bleeding risk associated with abnormal ROTEM indicates hemostatic failure or is a proxy for disease severity requires additional study.
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Paracetamol accounted for a weighted mean of 55.7% (range 50.0-77.8%) of severe acute liver injury (ALI) and/or ALF.
“Overall, paracetamol accounted for a weighted mean of 55.7% (range 50.0-77.8%) of severe acute liver injury (ALI) and/or ALF [201-208] and 7.3% (range 1.2-29.2%) of drug-induced liver injury (DILI) [209-219] (see Figure 7).”
From Paracetamol (acetaminophen) overdose and hepatotoxicity: mechanism, treatment, prevention measures, and estimates of burden of disease (2023) · cites this paper as [208]
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- Authors
- Stravitz, R. T., Fontana, R. J., Meinzer, C., Durkalski‐Mauldin, V., Hanje, A. J., Olson, J., Koch, D., Hamid, B., Schilsky, M. L., McGuire, B., Ganger, D., Liou, I., Karvellas, C. J., Rule, J. A., Lisman, T., Clasen, K., Reuben, A., Cripps, M., Lee, W. M., & ALF Study Group
- Affiliations
- Virginia Commonwealth University (US)
- University of Michigan (US)
- Medical University of South Carolina (US)
- The Ohio State University (US)
- University of Kansas Medical Center (US)
- University of California, San Francisco (US)
- Yale University (US)
- University of Alabama (US)
- Northwestern University (US)
- University of Washington (US)
- University of Alberta (CA)
- The University of Texas Southwestern Medical Center (US)
- University of Groningen (NL)
- Bristol-Myers Squibb (United States) (US)
- Corresponding author
- Stravitz, R. Todd
- ORCID
- Venue
- Hepatology
- Published
- 2021-08
- Volume
- 74
- Issue
- 2
- Pages
- 937-949
- ISSN
- 0270-9139 (ISSN-L)
- 1527-3350
- PMC
- PMC10668528
- OpenAlex
- W3132957741
- Cited by
- 50
- References
- 29
- Citations by year
- 2026: 4 · 2025: 12 · 2024: 13 · 2023: 11 · 2022: 9 · 2021: 1
- FWCI
- 6.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Funders
- Alexion Pharmaceuticals
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK058369, U‐01 58369, U01DK058369)
- Topics
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Trauma, Hemostasis, Coagulopathy, Resuscitation
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Keywords
- acute liver injury, acute liver failure, coagulopathy, bleeding complications, rotational thromboelastometry, hemostasis, thrombus formation, acetaminophen hepatotoxicity, hepatic encephalopathy, renal replacement therapy, disease severity, mortality, liver transplantation
- MeSH terms
- Acetaminophen, Adolescent, Adult, Aged, Blood Coagulation Disorders, Female, Hemorrhage, Humans, Male, Middle Aged, Severity of Illness Index, Thrombelastography, Liver Failure, Acute, Young Adult, Chemical and Drug Induced Liver Injury
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