title: Discrepancy between latex and ELISA D-dimer values in sepsis may be caused by human neutrophil elastase.
abstract: We have recently shown that D-dimers are degraded by human neutrophil elastase (HNE) in vitro, causing rapid decrease in the D-dimer levels measured by a Latex test, but not with an ELISA test employing the same monoclonal antibody against D-dimer. To see if such discrepant D-dimer concentrations occurred in patients with high HNE concentration, we examined 80 plasma samples from 8 patients with sepsis with a Latex and an ELISA test and calculated the ratio between the D-dimer values obtained with the two tests. Twenty healthy pregnant and twenty pre-eclamptic patients, who are known to have raised D-dimer but low HNE concentrations, were chosen as controls. HNE levels were estimated by determining the HNE-alpha 1-proteinase inhibitor complex (HNE-A1PI) concentration. HNE-A1PI concentration was increased in sepsis patients compared with pre-eclamptic patients (p < 0.0005) and healthy pregnant women (p < 0.0005). In sepsis patients, the D-dimer results were skewed towards lower ratios between Latex and ELISA values compared to pre-eclamptic patients (p = 0.008) and healthy pregnant women (p = 0.0001). In plasma samples from patients with the largest discrepancy between Latex and ELISA D-dimer values, Western blotting with immunostaining indicated degradation of D-dimers to D-like fragments similar to those observed following degradation of cross-linked fibrin by HNE in vitro. We conclude that in sepsis patients there is a marked discrepancy between Latex and ELISA D-dimer values that may be caused by HNE. In such patients Latex D-dimer assays may cause severe underestimation of fibrinolysis.
authors.affiliation: Department of Pulmonary Medicine, Ullevål Hospital, University of Oslo, Norway. Edvin.Bach-Gansmo@ioks.uio.no
authors.forename: E T
authors.initials: ET
authors.lastname: Bach-Gansmo
authors.forename: O
authors.initials: O
authors.lastname: Strand
authors.forename: H C
authors.initials: HC
authors.lastname: Godal
authors.forename: F
authors.initials: F
authors.lastname: Wisløff
authors.forename: O H
authors.initials: OH
authors.lastname: Skjønsberg
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis*; D005342:Fibrinolysis; D006801:Humans; D066298:In Vitro Techniques; D007841:Latex Fixation Tests / Q000379:methods*; D019272:Leukocyte Elastase / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000201:enzymology; D011225:Pre-Eclampsia / Q000097:blood; D011247:Pregnancy; D018805:Sepsis / Q000097:blood* / Q000201:enzymology; D000515:alpha 1-Antitrypsin / Q000032:analysis
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D000515:alpha 1-Antitrypsin; C036309:fibrin fragment D; D019272:Leukocyte Elastase