title: 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.
  
  
  CONCLUSIONS
  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.
authors: Section of Hepatology and Hume-Lee Transplant Center, Virginia Commonwealth University, Richmond, VA, USA. rstravit@vcu.edu
authors: R Todd
authors: RT
authors: Stravitz
authors: Regina
authors: R
authors: Bowling
authors: Robert L
authors: RL
authors: Bradford
authors: Nigel S
authors: NS
authors: Key
authors: Sam
authors: S
authors: Glover
authors: Leroy R
authors: LR
authors: Thacker
authors: Don A
authors: DA
authors: Gabriel
mesh_terms: D000328:Adult; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D005260:Female; D006501:Hepatic Encephalopathy / Q000097:blood*; D006801:Humans; D017114:Liver Failure, Acute / Q000150:complications*; D008297:Male; D008875:Middle Aged; D040201:Platelet Membrane Glycoprotein IIb / Q000097:blood; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood / Q000209:etiology*; D013925:Thromboplastin / Q000378:metabolism
chemical_list: D040201:Platelet Membrane Glycoprotein IIb; D013925:Thromboplastin
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