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Antibodies From Patients With Heparin-Induced
Thrombocytopenia/Thrombosis Recognize Different Epitopes on Heparin:
Platelet Factor 4
Jang-Soo Suh,
Richard H. Aster, and
Gian P. Visentin
From the Blood Research Institute, The Blood Center of Southeastern
Wisconsin, Milwaukee; and the Departments of Medicine and Pathology,
Medical College of Wisconsin, Milwaukee, WI.
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.
Blood, Vol. 91 No. 3 (February 1), 1998:
pp. 916-922
© 1998 by The American Society of Hematology.
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