title: Low-grade endotoxemia and clotting activation in the early phase of pneumonia.
abstract: Community-acquired pneumonia (CAP) is associated with an increased risk of arterial and venous thrombosis but the underlying pathophysiological mechanisms are still unclear. We investigated if, in patients with CAP, a pro-thrombotic state does exist and its relationship with serum levels of endotoxins.
  
  
  
  A total of 104 consecutive patients with CAP were prospectively recruited and followed up until discharge. At admission and at discharge, serum endotoxins, systemic markers of clotting activation and zonulin, a marker of gut permeability, were analysed. Hospitalized patients matched for gender, age and comorbidities but without infections were used as control.
  
  
  
  At admission, CAP patients showed higher plasma levels of F1+2, a marker of thrombin generation (P = 0.023), and lower levels of protein C (PC; P < 0.001) and activated PC (aPC) (P < 0.001) compared with controls. At discharge, plasma levels of both PC and aPC significantly increased while F1+2significantly decreased (P < 0.001). Baseline serum endotoxins and zonulin were higher in CAP patients than controls (P < 0.001) and significantly decreased at discharge; a significant correlation between serum endotoxins and zonulin was detected (R = 0.575; P < 0.001) CONCLUSION: This study provides the first evidence that CAP patients disclose an ongoing pro-thrombotic state and suggests a role for endotoxemia in determining enhanced thrombin generation.
authors.affiliation: Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Cangemi
authors.affiliation: Coagulation Service & Thrombosis Research Unit, Scientific Institute San Raffaele, Milano, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Della Valle
authors.affiliation: Department of Cardiovascular, Respiratory, Nephrology, Anesthesiology and Geriatric Sciences, Sapienza University of Rome, Rome, Italy.
authors.forename: Camilla
authors.initials: C
authors.lastname: Calvieri
authors.affiliation: Infectious and Tropical Diseases Unit, Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Gloria
authors.initials: G
authors.lastname: Taliani
authors.affiliation: Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS San Raffaele Pisana, Rome, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Ferroni
authors.affiliation: Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Falcone
authors.affiliation: Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Carnevale
authors.affiliation: Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Bartimoccia
authors.affiliation: Coagulation Service & Thrombosis Research Unit, Scientific Institute San Raffaele, Milano, Italy.
authors.forename: Armando
authors.initials: A
authors.lastname: D'Angelo
authors.affiliation: Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy. francesco.violi@uniroma1.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Violi
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation; D001780:Blood Coagulation Tests / Q000379:methods; D002772:Cholera Toxin / Q000097:blood*; D017714:Community-Acquired Infections / Q000097:blood / Q000150:complications / Q000503:physiopathology; D019446:Endotoxemia / Q000175:diagnosis*; D004731:Endotoxins / Q000097:blood*; D005260:Female; D006242:Haptoglobins; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007558:Italy; D008297:Male; D008875:Middle Aged; D010539:Permeability; D011014:Pneumonia / Q000097:blood / Q000150:complications / Q000503:physiopathology; D011446:Prospective Studies; D011498:Protein Precursors; D013927:Thrombosis / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control
chemical_list: D015415:Biomarkers; D004731:Endotoxins; D006242:Haptoglobins; D011498:Protein Precursors; C408043:zonulin; D002772:Cholera Toxin
keywords: endotoxin; pneumonia; protein C; thrombosis; zonulin