Heparin-induced thrombocytopenia: IgG binding to PF4-heparin complexes in the fluid phase and cross-reactivity with low molecular weight heparin and heparinoid.
Early diagnosis of heparin-induced thrombocytopenia (HIT) is essential to reduce morbidity and mortality. We report an enzyme immunoassay which detects the binding of HIT IgG to PF4-heparin in the fluid phase. Our fluid phase assay produces consistently low background and can detect low levels of anti-PF4-heparin. It is suited to testing alternative anticoagulants because, unlike in an ELISA, a clearly defined amount of antigen is available for antibody binding. We were able to detect anti-PF4-heparin IgG in 26/28 (93%) HIT patients. We investigated cross-reactivity of anti-PF4-heparin antibodies with PF4 complexed to alternative heparin-like anticoagulants. Low molecular weight heparins cross-reacted with 23/26 (88%) of the sera from HIT patients while half of the HIT sera weakly cross-reacted with PF4-danaparoid (Orgaran). The thrombocytopenia and thrombosis of most of these patients resolved during danaparoid therapy, indicating that detection of low affinity antibodies to PF4-danaparoid by immunoassay may not be an absolute contraindication for danaparoid administration.
Centre for Thrombosis and Vascular Research, Department of Haematology, Prince of Wales Hospital, Randwick, NSW, Australia.
P M
PM
Newman
R L
RL
Swanson
B H
BH
Chong
D000925:Anticoagulants / Q000009:adverse effects*; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D006493:Heparin / Q000009:adverse effects; D006495:Heparin, Low-Molecular-Weight / Q000276:immunology; D006496:Heparinoids / Q000276:immunology; D006801:Humans; D007124:Immunoenzyme Techniques; D007074:Immunoglobulin G / Q000097:blood*; D010978:Platelet Factor 4 / Q000378:metabolism*; D011485:Protein Binding; D013921:Thrombocytopenia / Q000097:blood / Q000139:chemically induced*; D016896:Treatment Outcome
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D006496:Heparinoids; D007074:Immunoglobulin G; D010978:Platelet Factor 4; D006493:Heparin