Antiplatelet factor 4/heparin antibodies in patients with gram negative bacteremia

Georgios Pongas, Swapan Kumar Dasgupta, Perumal Thiagarajan

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Heparin-induced thrombocytopenia (HIT) is an antibody-mediated syndrome of thrombocytopenia and prothrombotic state that follows exposure to heparin. However, spontaneous HIT has been described in the setting of infection, without evidence of previous heparin administration. Since PF4 binds to lipid A portion of lipopolysaccharide, we tested for the presence of antiPF4/heparin antibodies in patients with gram-negative bacteremia. Patients with bacteremia had higher titers of antiPF4/heparin antibodies compared to normal controls 26.3 ± SD 34 units, N = 32 versus 6.3 ± SD 2.38 units, N = 10, P = 0.001. FITC-labeled PF4 interacted with lipopolysaccharide in a concentration-dependent manner as determined by quenching of the emission spectrum following excitation at λ 488. In addition, immunoaffinity purified antiPF4/Heparin antibodies from 3 patients with HIT cross-reacted with PF4/heparin complex. These results show that PF4/LPS complex is immunogenic and can elicit cross-reacting antibodies against PF4/Heparin, providing an explanation for the presence of these antibodies in individuals, who were never been exposed to heparin before. These antibodies may also be at least partly responsible for the thrombocytopenia associated with infection.

Original languageEnglish (US)
Pages (from-to)217-220
Number of pages4
JournalThrombosis Research
Volume132
Issue number2
DOIs
StatePublished - Aug 2013

Bibliographical note

Funding Information:
GP and PT designed and perform the experiments and wrote the paper. SKG isolated the PF4 and performed fluorescence measurements. This study was supported in part by grants from the Department of Veterans Affairs (to PT) and by a grant from the National Blood Foundation (to SKD).

Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.

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