title: The clinical utility of fibrin-related biomarkers in sepsis.
abstract: Sepsis is associated with systemic inflammatory responses and induction of intravascular fibrin formation. Our aim is to investigate whether three fibrin-related markers (FRM) reflect the extent of coagulation activation in vivo and evaluate their clinical usefulness in identifying as well as monitoring patients with sepsis. Fibrin-degradation products (FDP), D-dimer and soluble fibrin monomer assays were measured on plasma samples from patients in the ICU with sepsis (n = 37), systemic inflammatory response syndrome (SIRS) (n = 35) and healthy individuals (n = 15). The levels were correlated with each other and also with fibrinogen, prothrombin time, platelets and antithrombin III. Clinical correlation was also performed for the diagnosis of sepsis and longitudinal monitoring for survival or death.There was strong correlation between the three FRM (r = 0.38-0.93, P < 0.0001) with only fibrin monomer correlating significantly with prothrombin time, fibrinogen and platelet levels. Clinically, all three FRM could discriminate between patients with sepsis, SIRS and healthy individuals with FDP, and D-dimer showing statistical significance (P < 0.05). No FRM predicted outcome from a single measurement but FDP was significantly able to predict patient survival from serial samples [mean FDP (μg/ml) from 35.36 to 21.37 (first to third ICU-day), P < 0.05]. Fibrin monomer appears the most sensitive indicator of coagulation activation, whereas D-dimer and FDP levels can significantly differentiate ICU patients with sepsis from those without. In addition, FDP would be preferable for monitoring with its statistically significant time-dependent prediction of survival or death from sepsis.
authors.affiliation: aLiverpool College bDepartments of Biostatistics cDepartment of Clinical Infection, Microbiology and Immunology, University of Liverpool dDepartment of Blood Sciences, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK.
authors.forename: Julien M H
authors.initials: JM
authors.lastname: Toh
authors.forename: Gie
authors.initials: G
authors.lastname: Ken-Dror
authors.forename: Colin
authors.initials: C
authors.lastname: Downey
authors.forename: Simon T
authors.initials: ST
authors.lastname: Abrams
mesh_terms: D000368:Aged; D000990:Antithrombin III / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D003937:Diagnosis, Differential; D005260:Female; D005337:Fibrin / Q000378:metabolism; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011517:Prothrombin Time; D018805:Sepsis / Q000097:blood* / Q000175:diagnosis / Q000401:mortality; D016019:Survival Analysis; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood* / Q000175:diagnosis / Q000401:mortality
chemical_list: D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D; C011468:fibrinmonomer; D000990:Antithrombin III; D005337:Fibrin