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 NVP-AUY922 supplier 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. Conclusion: 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. (HEPATOLOGY 2013;) Acute liver failure (ALF), the clinical syndrome subsequent to acute liver injury (ALI), is characterized by coagulopathy, hepatic encephalopathy

(HE), and, frequently, death without liver transplantation (LT).1 An intense systemic inflammatory response find more syndrome (SIRS),2 often AZD5363 in the absence of infection, predicts multiorgan system failure (MOSF) and death.3 Although proinflammatory cytokines originating from the necrotic liver may trigger the systemic complications of ALF, mediators of the syndrome are incompletely defined, and others with effects on vascular endothelium and hemostasis likely coexist.4 Although abnormalities in hemostasis are an invariable feature of ALF syndrome, patients rarely develop bleeding complications despite dramatically elevated international normalized ratio of prothrombin time (INR).5 Indeed, patients with ALF appear more prone to thrombotic, rather than bleeding, complications,6 and intrahepatic thrombosis may exacerbate the initial injury.7 Recently, we6, 8 and others9 have suggested that patients with ALF generally maintain normal or hypercoagulable global hemostasis, as determined by thromboelastography (TEG) and thrombin generation assays. Moreover, maximal clot strength by TEG increases in proportion to the number of SIRS components, possibly resulting from increased release of factor VIII and von Willebrand factor from activated/injured endothelial cells (ECs),10 providing a plausible explanation for the absence of bleeding, even in the most critically ill subjects with the highest INR.