GENERATION OF ANTIBODIES TO HEPARIN-PF4 COMPLEXES WITHOUT THROMBOCYTOPENIA IN PATIENTS TREATED WITH UNFRACTIONATED OR LOW-MOLECULAR-WEIGHT HEPARIN

The incidence of antibodies to heparin-PF4 complexes (H-PF4) has been evaluated in patients who were under heparin therapy for more than 7 d ays: 100 patients treated with unfractionated heparin (UH) and 100 pat ients with low-molecular-weight heparin (LMWH), The presence of antibo dies was identified in 17% of the former group and 8% of the latter, I n both the UH and the LMWH groups, IgM antibodies were found in all bu t four patients who showed IgA antibodies. IgG isotypes were only dete cted in five patients and were consistently associated to either IgM o r IgA antibodies, The follow-up of H-PF4 antibodies in 76 patients tre ated with UH from 1 to greater than or equal to 12 days showed a relat ionship between the incidence of antibodies and the duration of therap y, Despite the presence of anti-H-PF4 antibodies there was no thromboc ytopenia (<150 10(9)/L) in the patients, A significant drop of platele ts requiring the discontinuation of heparin was observed, however, in three patients, but their platelet count consistently remained >150 10 (9)/L, Our study demonstrates that the induction of antibodies to H-PF 4 is a frequent phenomenon in patients treated with UH or with LMWH, T he absence of thrombocytopenia and of clinical complications in these patients demonstrates that other conditions must be associated with H- PF4 antibodies for inducing type II HIT: optimal concentrations of hep arin and PF4 in the blood circulation to allow the formation of macrom olecular H-PF4 complexes, presence of activated platelets that present an increased binding of H-PF4 complexes, increased expression of Fc g amma RIIA receptors, or presence of their H 131 phenotype, We conclude that the measurement of antibodies to H-PM complexes allows the detec tion of hepar-intreated patients at risk of developing type II HIT. (C ) 1996 Wiley-Liss, Inc.