Abstract
Heparin-induced thrombocytopenia (HIT), with or without thrombosis, is a common and
often serious complication of heparin therapy. Platelet-activating, heparin-induced
antibodies characteristic of HIT are thought to be specific for complexes formed between
platelet factor 4 (PF4) and heparin, and such complexes are routinely used for antibody
detection. We studied the binding of HIT antibodies to PF4 complexed with heparin
fractions of uniform molecular size or linear polyanions other than heparin and found
that many compounds other than heparin form complexes with PF4 that are suitable for
antibody detection, provided they carry strong negative charges spaced about 0.5 nm
apart along the molecular backbone and are of sufficient length to span about 40%
of the circumference of the PF4 tetramer. Polyvinyl phosphonate was among the compounds
that were equivalent to heparin. Thus neither a polysaccharide chain nor sulfate side
groups—the hallmarks of heparin structure—are required for HIT antibody detection.
The findings support the view that antibodies associated with HIT are specific for
conformational changes that take place in the positively charged PF4 molecule when
it reacts with a suitable, linear polyanion. (J Lab Clin Med 2001;138:22-31)
Abbreviations:
ELISA (enzyme-linked immunospecific assay), GAG (glycosaminoglycan), HF (heparin fragment), HIT (heparin-induced thrombocytopenia), IgG (immunoglobulin G), LMWH (low-molecular-weight heparin), OD (optical density), PAS (polyanethyl sulfonate), PBS (phosphate-buffered saline solution), PBS-Tween (PBS containing 0.05% Tween-20), PEG (polyethylene glycol), PF4 (platelet factor 4), PG (poly-D -glutamic acid), PSS (polystyrene sulfonate), PVP (polyvinyl phosphate), PVPN (polyvinyl phosphonate), PVS (polyvinyl sulfate), PVSN (polyvinyl sulfonate), SRA (serotonin release assay), UFH (unfractionated heparin)To read this article in full you will need to make a payment
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Article info
Publication history
Accepted:
March 7,
2001
Received in revised form:
January 24,
2001
Received:
June 15,
2000
Footnotes
☆Supported by grants HL-13629, HL-44612, and HL-64704 and by Clinical Investigator Award HL-03464 from the National Heart, Lung, and Blood Institute.
☆☆Reprint requests: Gian Paolo Visentin, MD, Blood Research Institute of The Blood Center of Southeastern Wisconsin, PO Box 2178, Milwaukee, WI 53201-2178.
Identification
Copyright
© 2001 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
