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Role of procoagulant microparticles in mediating complications and outcome of acute liver injury/acute liver failure.

ABSTRACT: Microparticles (MPs), membrane fragments of 0.1-1.0 μm, are derived from many cell types in response to systemic inflammation. Acute liver failure (ALF) is a prototypical syndrome of systemic inflammatory response syndrome (SIRS) associated with a procoagulant state. We hypothesized that patients with ALF develop increased procoagulant MPs in proportion to the severity of systemic complications and adverse outcome. Fifty patients with acute liver injury (ALI), 78% of whom also had hepatic encephalopathy (HE; ALF), were followed until day 21 after admission. MPs were characterized by Invitrox Sizing, Antigen Detection and Enumeration, a light-scattering technology that can enumerate MPs as small as 0.15 μm, and by flow cytometry. Procoagulant activity was assessed by a functional MP-tissue factor (MP-TF) assay. Sixteen patients (32%) died and 27 (54%) recovered without liver transplantation (LT). Total MPs (0.15-1.0 μm) were present in nearly 19-fold higher concentrations in ALI/ALF patients, compared to healthy controls (P < 0.0001). MP-TF assays revealed high procoagulant activity (9.05 ± 8.82 versus 0.24 ± 0.14 pg/mL in controls; P = 0.0008). MP concentrations (0.28-0.64 μm) were higher in patients with the SIRS and high-grade HE, and MPs in the 0.36-0.64-μm size range increased in direct proportion to SIRS severity (P < 0.001) and grade of HE (P < 0.002). Day 1 MPs (0.28-0.64 μm) correlated with laboratory predictors of death/LT (higher phosphate and creatinine; lower bicarbonate), and day 1 and 3 MPs were higher in patients who died or underwent LT, compared to spontaneous survivors (P ≤ 0.01). By flow cytometry, 87% of patients had circulating CD41(+) MPs, indicating platelet origin.Highly procoagulant MPs of specific size ranges are associated with the SIRS, systemic complications, and adverse outcome of ALI/ALF. MPs may contribute to the multiorgan system failure and high mortality of ALF.

SUBMITTER: Stravitz RT

PROVIDER: S-EPMC5571831 | biostudies-other | 2013 Jul

REPOSITORIES: biostudies-other

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Project description:In patients with acute liver failure (ALF), elevated prothrombin time and thrombocytopenia can fuel a perception of a bleeding tendency. However, the incidence, site, risk factors, and clinical significance of bleeding complications have not been quantified in a large cohort of patients with ALF. We studied 1,770 adult patients enrolled in the ALF Study Group Registry between 1998 and 2016. Bleeding complications and blood component transfusions were collected for 7 days after admission. The relationship of bleeding complications to 21-day mortality was assessed. Despite a median international normalized ratio of 2.7 and platelet count of 96 × 109 /L on admission, bleeding complications were observed in only 187 patients (11%), including 173 spontaneous and 22 postprocedural bleeding episodes. Eighty-four percent of spontaneous bleeding episodes were from an upper gastrointestinal source and rarely resulted in red blood cell transfusion. Twenty patients experienced an intracranial bleed; half of these occurred spontaneously and half after intracranial pressure monitor placement, and this was the proximate cause of death in 20% and 50%, respectively. Bleeders and patients who received red blood cell transfusions were more acutely ill from extrahepatic organ system failure but not from hepatocellular failure. Consistent with this observation, bleeding complications were associated with lower platelet counts but not higher international normalized ratio. Transfusion of any blood component was associated with nearly 2-fold increased death or need for liver transplantation at day 21, but bleeding complications were the proximate cause of death in only 5% of cases. CONCLUSIONS:Despite a perceived bleeding diathesis, clinically significant bleeding is uncommon in patients with ALF; bleeding complications in patients with ALF are markers of severe systemic inflammation rather than of coagulopathy and so portend a poor prognosis. (Hepatology 2018;67:1931-1942).

Project description:BackgroundHepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) is an important type of liver failure in Asia. There is a direct relationship between HBV-ACLF and gastrointestinal barrier function. However, the nutritional status of HBV-ACLF patients has been poorly studied.AimTo investigate the nutritional risk and nutritional status of HBV-ACLF patients and evaluated the impact of nutritional support on the gastrointestinal barrier and 28-d mortality.MethodsNutritional risk screening assessment and gastrointestinal barrier biomarkers of patients with HBV-ACLF (n = 234) and patients in the compensatory period of liver cirrhosis (the control group) (n = 234) were compared during the period between 2016 and 2018. Changes were analyzed after nutritional support in HBV-ACLF patients. Valuable biomarkers have been explored to predict 28-d death. The 28-d survival between HBV-ACLF patients with nutritional support (n = 234) or no nutritional support (2014-2016) (n = 207) was compared.ResultsThe nutritional risk of the HBV-ACLF patients was significantly higher than that of the control group. The nutritional intake of the patients with HBV-ACLF was lower than that of the control group. The decrease in skeletal muscle and fat content and the deficiency of fat intake were more obvious (P < 0.001). The coccus-bacillus ratio, secretory immunoglobulin A, and serum D-lactate were significantly increased in HBV-ACLF patients. The survival group had a lower nutritional risk, lower D-lactate, and cytokine levels (endotoxin, tumor necrosis factor alpha, interleukin-10, and interleukin-1). Interleukin-10 may be a potential predictor of death in HBV-ACLF patients. The 28-d survival of the nutritional support group was better than that of the non-nutritional support group (P = 0.016).ConclusionPatients with HBV-ACLF have insufficient nutritional intake and high nutritional risk, and their intestinal barrier function is impaired. Individualized and dynamic nutritional support is associated with a better prognosis of 28-d mortality in HBV-ACLF patients.

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Role of procoagulant microparticles in mediating complications and outcome of acute liver injury/acute liver failure.

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