title: Thrombocytopenia Is Associated With Multi-organ System Failure in Patients With Acute Liver Failure.
abstract: OBJECTIVE
  Acute liver failure (ALF) is a syndrome characterized by an intense systemic inflammatory response (SIRS) and multi-organ system failure (MOSF). Platelet-derived microparticles increase in proportion to the severity of the SIRS and MOSF, and are associated with poor outcome. We investigated whether patients with ALF develop thrombocytopenia in proportion to the SIRS, MOSF, and poor outcome.
  
  
  METHODS
  In a retrospective study, we collected data on the post-admission platelet counts of 1598 patients included in the ALF Study Group Registry from 1998 through October 2012. We investigated correlations between platelet counts and clinical features of ALF, laboratory test results, and outcomes. Of the patients studied, 752 (47%) survived without liver transplantation, 390 (24%) received liver transplants, and 517 (32%) died.
  
  
  RESULTS
  In patients with SIRS, platelet counts decreased 2 to 7 days after admission, compared with patients without SIRS (P ≤ .001). Patients with abnormal levels of creatinine, phosphate, lactate, or bicarbonate had significantly lower platelet counts than patients with normal levels of these laboratory values (all P ≤ .001). The decrease in platelets during days 1 to 7 after admission was proportional to the grade of hepatic encephalopathy and requirement for vasopressor and renal replacement therapy. Although platelet numbers decreased after admission in the overall population, platelets were significantly lower 2 to 7 days after admission in patients with outcomes of death or liver transplantation than in patients who made spontaneous recoveries and survived. In contrast, international normalized ratios over time were not associated with SIRS, laboratory test results associated with poor outcomes, grade of hepatic encephalopathy, or requirement for renal replacement therapy.
  
  
  CONCLUSIONS
  The development of thrombocytopenia in patients with ALF is associated with the development of MOSF and poor outcome. We speculate that SIRS-induced activation of platelets, yielding microparticles, results in clearance of platelet remnants and subsequent thrombocytopenia.
authors.affiliation: Section of Hepatology and Hume-Lee Transplant Center, Virginia Commonwealth University, Richmond, Virginia. Electronic address: Richard.Stravitz@VCUHealth.ORG.
authors.forename: R Todd
authors.initials: RT
authors.lastname: Stravitz
authors.affiliation: Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Caitlyn
authors.initials: C
authors.lastname: Ellerbe
authors.affiliation: Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Valerie
authors.initials: V
authors.lastname: Durkalski
authors.affiliation: Division of Gastroenterology, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Adrian
authors.initials: A
authors.lastname: Reuben
authors.affiliation: Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Ton
authors.initials: T
authors.lastname: Lisman
authors.affiliation: University of Texas, Southwestern Medical Center, Dallas, Texas.
authors.forename: William M
authors.initials: WM
authors.lastname: Lee
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D017114:Liver Failure, Acute / Q000150:complications* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D018746:Systemic Inflammatory Response Syndrome / Q000150:complications* / Q000401:mortality / Q000473:pathology*; D013921:Thrombocytopenia / Q000175:diagnosis* / Q000209:etiology
keywords: Blood Cell; Hemostasis; INR; Plasma Membrane Fragmentation