Medical College of Wisconsin
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Antibodies from patients with heparin-induced thrombocytopenia/thrombosis recognize different epitopes on heparin: platelet factor 4. Blood 1998 Feb 01;91(3):916-22 PMID: 9446652

Pubmed ID

9446652

Abstract

Antibodies associated with heparin-induced thrombocytopenia/ thrombosis (HITT) are now thought to be specific for complexes formed between heparin and platelet factor 4 (PF4), a basic protein found normally in platelet alpha granules. How these antibodies cause thrombocytopenia and, in some patients, thrombosis, is not fully understood, in part because purified antibodies that could be labeled and used as probes to characterize target epitopes have not been available. We developed a novel method for antibody purification involving binding to and elution from PF4 complexed to heparin immobilized by end-linkage (EL) to a solid phase. Isolated antibodies were functional and after biotinylation, reacted with heparin: PF4 complexes in the same manner as unlabeled antibodies. Using these probes, we found that antibodies from 11 patients with HITT recognized two, and probably three, distinct sites on heparin: PF4 complexes. The antibodies did not bind to PF4 complexed with heparin immobilized by multiple chemical cross-linkages, suggesting that the heparin molecule must be in a flexible, relatively unconstrained state to react with PF4 in such a way as to create sites for HITT antibody binding.

Author List

Suh JS, Aster RH, Visentin GP

Author

Richard H. Aster MD Professor in the Medicine department at Medical College of Wisconsin




Scopus

2-s2.0-0032006889   88 Citations

MESH terms used to index this publication - Major topics in bold

Amino Acid Sequence
Antibodies
Antibody Specificity
Biotinylation
Cross-Linking Reagents
Epitopes
Heparin
Humans
Microspheres
Molecular Sequence Data
Peptide Fragments
Platelet Factor 4
Thrombocytopenia
Thrombosis
jenkins-FCD Prod-353 9ccd8489072cb19f5b9f808bb23ed672c582f41e