Heparin-associated thrombocytopenia: immune complexes are attached to the platelet membrane by the negative charge of highly sulphated oligosaccharides.
The interaction of sulphated oligosaccharides (SO) with platelets and the antibody of heparin-associated thrombocytopenia (HAT type II) was investigated. 3H-heparin binding to platelets was inhibited by different SO, depending on their grade of sulphation. Dextran sulphate, pentosan polysulphate, and heparin were more effective than were LMW heparins. De-N-sulphated heparin and a LMW heparinoid (Org 10172) had no effect. Platelets preincubated with high-grade SO and washed, released serotonin in the presence of HAT sera without additional heparin. Platelets preincubated with HAT sera and then washed were not activated when heparin was added. Only high-grade SO which inhibited heparin binding to platelets caused platelet activation with HAT sera. However, low- and high-grade SO in high concentrations (0.11 g/l) inhibited serotonin release induced by HAT sera and heparin. 32P-phosphorylation of platelet proteins was enhanced by HAT-IgG and heparin and by heat-aggregated IgG, and was inhibited by the moab IV.3. High SO concentrations inhibited only the effect of HAT-IgG and not that of aggregated IgG. We assume that the antigen in HAT involves a releasable platelet protein with a binding site for SO. This was corroborated by studies with an anti-platelet factor 4 antibody causing Fc-receptor dependent platelet activation inhibitable by high SO concentrations.
Greinacher
A
A
Institute for Clinical Immunology and Transfusion Medicine, Rudolf-Buchheim-Institut für Pharmakologie, Justus Liebig University, Giessen, Germany.
Michels
I
I
Liebenhoff
U
U
Presek
P
P
Mueller-Eckhardt
C
C
D000936:Antigen-Antibody Complex / Q000378:metabolism*; D001667:Binding, Competitive; D001792:Blood Platelets / Q000378:metabolism* / Q000502:physiology; D002478:Cells, Cultured; D006493:Heparin / Q000009:adverse effects*; D006801:Humans; D009844:Oligosaccharides / Q000378:metabolism*; D010766:Phosphorylation; D010978:Platelet Factor 4 / Q000276:immunology; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000276:immunology
D000936:Antigen-Antibody Complex; D009844:Oligosaccharides; D010978:Platelet Factor 4; D006493:Heparin