Korean J Clin Pathol.  1997 Dec;17(6):944-955.

Characterization of Heparin:PF4 Isoantibody Interaction to Platelets in Heparin-Induced Thrombocytopenia/ Thrombosis

• Kim KY
• Chang YJ
• Suh JS
• Kim JS

Abstract

BACKGROUND: Heparin-induced thrombocytopenia/ thrombosis (HITT) is recognized as the most frequent and fatal symptom complexes in patients receiving heparin therapy. The antibodies of HITT are not directly bound to heparin but bound to complexes of heparin and platelet factor 4 (PF4) derived from platelet alpha-granules. That is, HITT IgG antibody-heparin-PF4 immune complexes are bound to FcgammaRII receptor of platelets, which induced thrombocytopenia. Some researches showed the antibodies reactive to platelets could be IgM or IgA as well as IgG. So in this study, the authors tried to explain the molecular basis of heparin-PF4-isoantibody complexes .
METHODS
In HITT patients who had received long-term heparin therapy, we determined HITT isoantibodies and titers using heparin:PF4 ELISA. When fifteen HITT patients with high titer antibodies (more than 1 : 100) were selected, reaction patterns of isoantibodies with the platelets were examined through serotonin release test and flow cytometry.
RESULTS
All patients showed one or more isotype antibodies and the most frequent isotype was IgGl (nine patients) . In the presence of optimal concentra pion of heparin and PF4, ten patients had antibodies which activated platelets, and all of them were positive in serotonin release test. Reactive plasmas had IgGl, IgG3, IgA or IgM antibodies, and each of them except one had IgGl. These platelet activations could be blocked in vitro by anti-IV.3 antibody. Non-reactive plasmas were negative In serotonin release assay nor had TgGl. The plasmas 4hat had two or more isoantibodies showed a similar pattern of the IgG antibody by flow cytometry.
CONCLUSIONS
The HITT antibodies can be all kinds of antibody isotopes, but IgA and IgM may not bind to the platelets directly. It seems to be possible only after reacting with heparin-PF4-IgG complexes.

MeSH Terms

Antibodies
Antigen-Antibody Complex
Blood Platelets
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Heparin
Humans
Immunoglobulin A
Immunoglobulin G
Immunoglobulin M
Isoantibodies
Isotopes
Mesons
Plasma
Platelet Activation
Platelet Factor 4
Serotonin
Thrombocytopenia
Thrombosis*
Antibodies
Antigen-Antibody Complex
Heparin
Immunoglobulin A
Immunoglobulin G
Immunoglobulin M
Isoantibodies
Isotopes
Platelet Factor 4
Serotonin