Heparin-associated thrombocytopenia: the effects of various intravenous IgG preparations on antibody mediated platelet activation--a possible new indication for high dose i.v. IgG.
The immunologic type of heparin-associated thrombocytopenia (HAT) is caused by antibodies which activate platelets via the Fc-receptor in the presence of polysulfated oligosaccharides. The antigen is formed by a releasable platelet protein (in many cases PF4) complexed to heparin. Since the role of GP IIb/IIIa in platelet activation by HAT antibodies is controversial, we investigated platelet activation by antibodies related to HAT. We used normal platelets and platelets from a patient with Glanzmann's thrombasthenia (GT) lacking GP IIb/IIIa. Heparin and sera from patients with HAT stimulated GT platelets in the same manner as determined by 14C-serotonin release and the changes in phosphorylation of p20 and p47. Platelet activation could be inhibited by an anti FcRII monoclonal antibody (IV. 3, Fab-fragments), and by Fc-fragments, but not by F(ab')2-fragments of human IgG. The effect of four different, commercially available preparations of intact i.v. IgG on the platelet activation by six HAT sera was investigated by 14C-serotonin release. The inhibitory effect was strongly dependent upon the manufacturing process. At a concentration of 20 mg/ml only IgG that had been subjected to low pH and traces of pepsin sufficiently inhibited platelet activation. IgG treated with polyethylenglycol or sulfitolysis was less effective, whereas beta-propiolactone-treated IgG almost completely lost the ability to inhibit platelet activation by antibodies related to HAT. We conclude that inhibition of GP IIb/IIIa-fibrinogen interaction is insufficient for preventing platelet activation in HAT.(ABSTRACT TRUNCATED AT 250 WORDS)
Greinacher
A
A
Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, FRG.
Liebenhoff
U
U
Kiefel
V
V
Presek
P
P
Mueller-Eckhardt
C
C
D000368:Aged; D004305:Dose-Response Relationship, Drug; D005260:Female; D006493:Heparin / Q000009:adverse effects*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007518:Isoantibodies / Q000097:blood*; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects* / Q000276:immunology; D010980:Platelet Membrane Glycoproteins / Q000172:deficiency; D012016:Reference Values; D013921:Thrombocytopenia / Q000139:chemically induced / Q000628:therapy*
D016756:Immunoglobulins, Intravenous; D007518:Isoantibodies; D010980:Platelet Membrane Glycoproteins; D006493:Heparin