Antibodies to platelet factor 4 - Heparin after cardiopulmonary bypass in patients anticoagulated with unfractionated heparin or a low-molecular-weight heparin - Clinical implications for heparin-induced thrombocytopenia

Background-Cardiopulmonary bypass (CPB) induces platelet activation with re lease of platelet factor 4 (PF4), and patients are exposed to high doses of heparin (H). We investigated whether this contributes to the development o f antibodies to H-PF4 and heparin-induced thrombocytopenia (HIT). Methods and Results-CPB was performed with unfractionated heparin (UFH) in 328 patients. After surgery, patients received UFH (calcium heparin, 200 IU .kg(-1).d(-1)) (group 1, n=157) or low-molecular-weight heparin (LMWH, Dalt eparin, 5000 TU once daily) (group 2, n=171). Eight days after surgery, ant ibodies to H-PF 1 were present in 83 patients (25.3%), 46 in group 1 and 37 in group 2 (P=0.12). Most patients (61%) had IgG 1 to H-PF4, but only 8 sa mples with antibodies induced platelet activation with positive results on serotonin release assay. HIT occurred in 6 patients in group 1, but no thro mbocytopenia was observed in subjects receiving LMWH, although 2 had high l evels of antibodies with positive serotonin release assay results. When ant ibodies to H-PF4 were present, mean platelet counts were lower only in pati ents with Fc gamma RIIA R/R-131 platelets. Conclusions-These results provide evidence that the development of antibodi es to H-PF4 after CPB performed with UFH is not influenced by the postopera tive heparin treatment. The antibodies associated with high risk of HIT are mainly IgG1, which is present at high titers in the plasma of patients con tinuously treated with UR-I.