[Platelet factor 4, target of anti-heparin antibodies: application to biological diagnosis of heparin-induced thrombopenia]

Abstract

Heparin-platelet factor 4 (H-PF4) complexes are the target for heparin-dependent antibodies present in most of heparin-induced thrombocytopenias (HIT). The highest reactivity is obtained with 27 IU of heparin per mg of PF4. Low molecular weight heparin (LMWH) and pentosane polysulphate can also form these complexes. Antibodies to H-PF4, may be of the IgG, IgA or IgM isotypes. In some HIT, IgGs are absent and only IgMs and/or IgAs are observed. These antibodies may also develop in heparin (15%) or LMWH (8%) treated patients in the absence of thrombocytopenia. IgGs rarely develop in these cases. Presence of antibodies to H-PF4 is therefore a risk factor for developing HIT. Development of pathology requires additional factors such as: PF4 and heparin at an optimised ratio allowing formation of macromolecular complexes; presence of activated platelets exposing increased Fc gamma RII-A and heparin receptors; His. 131 phenotype of Fc gamma RII-A; pre-thrombotic and/or inflammatory clinical manifestations. Assay of antibodies to H-PF4 improves HIT diagnosis and could be predictive for monitoring heparin-therapies.