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Anti‐protein S antibodies following a varicella infection: detection, characterization and influence on thrombin generation
Author(s) -
REGNAULT V.,
BOEHLEN F.,
OZSAHIN H.,
WAHL D.,
DE GROOT P. G.,
LECOMPTE T.,
DE MOERLOOSE P.
Publication year - 2005
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2005.01270.x
Subject(s) - protein c , antibody , thrombin , purpura fulminans , thrombomodulin , epitope , protein s , medicine , immunology , microbiology and biotechnology , chemistry , biology , platelet , surgery
Summary. Postinfectious purpura fulminans is a rare disease. Varicella is one of the precipitating conditions and we recently observed such a case. The 4‐year‐old child was found to have a severe transient protein S deficiency. By enzyme‐linked immunosorbent assay and surface plasmon resonance we first demonstrated that anti‐protein S antibodies were present and also transient. Next we characterized the epitopes against which these antibodies were directed and found that they predominantly recognized the N‐terminal part of protein S. Finally we showed by thrombography a transient dramatic hypercoagulable state as a result of thrombin being unregulated by the dynamic protein C inhibitory system: in vitro thrombin generation, in response to a low concentration of tissue factor, was almost insensitive to activated protein C up to 25 nmol L −1 on day 4 while it was normally sensitive on day 42. For the first time, we demonstrated a temporal relationship between protein S deficiency, antibodies to protein S and hypercoagulability, thus supporting the pathogenic role of these antibodies.