Changes in platelet levels and prognosis in patients with acute liver failure and late-onset hepatic failure

The therapeutic strategies for acute liver failure (ALF) and late-onset hepatic failure (LOHF) still have room for improvement. Recent studies have reported an association between platelets and the pathophysiology of ALF. In this study, we investigated changes in platelet levels and clinical findings in ALF and LOHF patients. We retrospectively investigated the clinical data of 62 patients with ALF and LOHF. We analyzed the association between changes in platelet levels for 7 days after admission and the prognosis in patients with ALF and LOHF. The factors associated with changes in platelet levels were also analyzed. The platelet levels on days 1, 3, and 7 were significantly lower in the patients who died or underwent liver transplantation than in the spontaneous survivors. Administration of recombinant thrombomodulin was associated with spontaneous survival. The platelet levels in patients who met the King’s College Hospital Criteria or the Japanese scoring system (JSS) for ALF ≥ 4 were significantly decreased 7 days after admission. The area under the receiver operating characteristic curve (AUROC) of a JSS score of 3 for predicting low platelet levels on day 7 was 0.903. Decreased platelet levels were associated with poor prognosis in patients with ALF and LOHF. The patients with low platelet levels and JSS scores on admission showed a high AUROC for predicting low platelet levels on day 7. Decreased platelet levels after admission may be a simple prognostic marker in ALF and LOHF patients.

[1]  Jiyuan Zhang,et al.  Low platelets: a new and simple prognostic marker for patients with hepatitis E virus-related acute liver failure , 2022, Hepatology International.

[2]  Y. Takikawa,et al.  Contrast‐Enhanced Ultrasonography–Based Hepatic Perfusion for Early Prediction of Prognosis in Acute Liver Failure , 2020, Hepatology.

[3]  C. Weston,et al.  The platelet receptor CLEC-2 blocks neutrophil mediated hepatic recovery in acetaminophen induced acute liver failure , 2020, Nature Communications.

[4]  K. Tachibana,et al.  Enhanced effect of recombinant human soluble thrombomodulin by ultrasound irradiation in acute liver failure , 2020, Scientific Reports.

[5]  K. Kawasaki,et al.  Thrombomodulin alfa prevents the decrease in platelet aggregation in rat models of disseminated intravascular coagulation. , 2019, Thrombosis research.

[6]  R. Jalan,et al.  Long‐term outcome in patients with acute liver failure , 2018, Liver international : official journal of the International Association for the Study of the Liver.

[7]  O. Yokosuka,et al.  Nationwide survey for acute liver failure and late-onset hepatic failure in Japan , 2018, Journal of Gastroenterology.

[8]  M. Manns,et al.  EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure. , 2017, Journal of hepatology.

[9]  William M. Lee,et al.  Thrombocytopenia Is Associated With Multi-organ System Failure in Patients With Acute Liver Failure. , 2016, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[10]  S. Takai,et al.  Recombinant human soluble thrombomodulin improved lipopolysaccharide/d-galactosamine-induced acute liver failure in mice. , 2015, Journal of pharmacological sciences.

[11]  I. Henderson,et al.  Inflammation drives thrombosis after Salmonella infection via CLEC-2 on platelets. , 2015, The Journal of clinical investigation.

[12]  Mitchell R. McGill,et al.  Platelets and protease-activated receptor-4 contribute to acetaminophen-induced liver injury in mice. , 2015, Blood.

[13]  W. Chang,et al.  Recombinant Thrombomodulin Inhibits Lipopolysaccharide-Induced Inflammatory Response by Blocking the Functions of CD14 , 2015, The Journal of Immunology.

[14]  N. Ohkohchi,et al.  Role of platelets in chronic liver disease and acute liver injury , 2014, Hepatology research : the official journal of the Japan Society of Hepatology.

[15]  Robert L. Bradford,et al.  Role of procoagulant microparticles in mediating complications and outcome of acute liver injury/acute liver failure , 2013, Hepatology.

[16]  Y. Kanda,et al.  Investigation of the freely available easy-to-use software ‘EZR' for medical statistics , 2012, Bone Marrow Transplantation.

[17]  S. Mochida,et al.  Acute liver failure in Japan: definition, classification, and prediction of the outcome , 2012, Journal of Gastroenterology.

[18]  Y. Takikawa,et al.  Diagnostic criteria of acute liver failure: A report by the Intractable Hepato‐Biliary Diseases Study Group of Japan , 2011, Hepatology research : the official journal of the Japan Society of Hepatology.

[19]  N. Hayashi,et al.  Thrombocytopenia exacerbates cholestasis-induced liver fibrosis in mice. , 2010, Gastroenterology.

[20]  Paul Yap,et al.  MELD score to predict outcome in adult patients with non‐acetaminophen‐induced acute liver failure , 2007, Liver international : official journal of the International Association for the Study of the Liver.

[21]  Yasuhiro Ohtomo,et al.  A multicenter, prospective validation of disseminated intravascular coagulation diagnostic criteria for critically ill patients: Comparing current criteria* , 2006, Critical care medicine.

[22]  Hiroshi Yamamoto,et al.  The N-terminal domain of thrombomodulin sequesters high-mobility group-B1 protein, a novel antiinflammatory mechanism. , 2005, The Journal of clinical investigation.

[23]  J. Farrell,et al.  The Management of Fulminant Hepatic Failure , 2001 .

[24]  C. Esmon Thrombomodulin as a model of molecular mechanisms that modulate protease specificity and function at the vessel surface , 1995, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[25]  R Williams,et al.  Early indicators of prognosis in fulminant hepatic failure. , 1989, Gastroenterology.

[26]  K. Fujiwara,et al.  Intravascular coagulation in acute liver failure in rats and its treatment with antithrombin III. , 1988, Gut.