Faculty Collaboration Database

Heparin is not required for detection of antibodies associated with heparin-induced thrombocytopenia/thrombosis. J Lab Clin Med 2001 Jul;138(1):22-31

Date

07/04/2001

Pubmed ID

11433225

DOI

10.1067/mlc.2001.115525

Scopus ID

2-s2.0-0034962770 (requires institutional sign-in at Scopus site)   121 Citations

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.

Author List

Visentin GP, Moghaddam M, Beery SE, McFarland JG, Aster RH

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

Antibody Specificity
Anticoagulants
Antigen-Antibody Reactions
Blood Platelets
Epitopes
Heparin
Heparitin Sulfate
Humans
In Vitro Techniques
Platelet Activation
Platelet Factor 4
Polyelectrolytes
Polymers
Polysaccharides
Polyvinyls
Thrombocytopenia
Thrombosis