Quantification of antithrombin isoform proportions in plasma samples of healthy subjects, sepsis patients, and in antithrombin concentrates.
Antithrombin (AT) circulates in plasma in two isoforms, AT-alpha (90-95%) and AT-beta (5-10%). AT isoform proportions were measured in plasma samples of 17 healthy subjects and 26 posttraumatic or postoperative septic patients, as well as in 4 commercially available AT concentrates. Total AT was immune-purified from plasma and concentrates. Micellar electrokinetic chromatography was used to analytically separate and quantify the isoforms. Compared with plasma samples of healthy donors, septic plasmas revealed significantly reduced AT activity (p < 0.001) and beta-isoform content (p < 0.05). AT-beta correlated inversely with urea and creatinine serum concentrations (p < 0.01), indicating a relationship between better renal function and higher beta-isoform content. beta-Isoform neither correlated with age, gender, and 28-day mortality, nor with plasma concentrations of various inflammatory and organ function parameters. The commercial AT concentrate, which is equivalent to the current WHO standard, had an AT-beta content close to that found in plasma of healthy subjects. The availability of this novel quantitative AT isoform assay allows, for the first time, a closer look at the role of AT isoforms in hemostasis and sepsis pathophysiology.
Römisch
Jürgen
J
Aventis Behring GmbH, Research, Marburg, Germany. Jurgen.Roemisch@octopharma.at
Dönges
Reiner
R
Stauss
Harald
H
Inthorn
Dietrich
D
Mühlbayer
Dieter
D
Jochum
Marianne
M
Hoffmann
Johannes  N
J
D000328:Adult; D000990:Antithrombin III / Q000032:analysis* / Q000302:isolation & purification / Q000592:standards; D015415:Biomarkers; D003404:Creatinine / Q000097:blood; D003505:Cyclodextrins / Q000494:pharmacology; D019040:E-Selectin / Q000097:blood; D019075:Electrophoresis, Capillary; D005260:Female; D006801:Humans; D007163:Immunosorbent Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D007668:Kidney / Q000503:physiopathology; D019272:Leukocyte Elastase / Q000097:blood; D008297:Male; D008823:Micelles; D008875:Middle Aged; D020033:Protein Isoforms / Q000097:blood / Q000172:deficiency; D018805:Sepsis / Q000097:blood* / Q000401:mortality; D014508:Urea / Q000097:blood; D047392:beta-Cyclodextrins
D015415:Biomarkers; D003505:Cyclodextrins; D019040:E-Selectin; D015850:Interleukin-6; D016209:Interleukin-8; D008823:Micelles; D020033:Protein Isoforms; D047392:beta-Cyclodextrins; D018799:Intercellular Adhesion Molecule-1; D014508:Urea; D000990:Antithrombin III; D003404:Creatinine; D019272:Leukocyte Elastase; C031215:betadex