Different platelet specificities of heparin-dependent platelet aggregating factors in heparin-associated immune thrombocytopenia.
Delayed onset heparin-associated thrombocytopenia (HAT) is thought to be a result of formation of antiplatelet antibodies which cause platelet aggregation in the presence of heparin. Platelet aggregation in response to serum from patients with HAT has been studied in platelet-rich plasma (PRP) from a panel of normal blood donors. Heparin-dependent aggregation with any HAT serum occurred in PRP from only some donors. PRP from the non-responding donors did, however, aggregate in the presence of heparin with other HAT sera. The same patterns of aggregation or lack of response to HAT sera were seen in washed platelet suspensions. Heparin (0.06-2 U/ml) did not cause aggregation in the presence of normal serum with PRP from these donors. However, in PRP from four of the 17 individuals studied, heparin (0.25-1 U/ml) alone caused rapid platelet aggregation and some HAT sera heated at 56 degrees C caused platelet aggregation without added heparin. Sub-aggregating concentrations of adrenaline could replace heparin in promoting aggregation by heated HAT sera in PRP of the other donors. HAT IgG showed the same platelet specificities as the serum in causing either heparin- or adrenaline-dependent aggregation. Thus in HAT, antibodies are directed towards different platelet antigens which are expressed differently in different individuals. Platelet activation by heparin and adrenaline either exposes these antigens or causes aggregation of antibody-coated platelets.
D000918:Antibody Specificity; D001779:Blood Coagulation Factors / Q000276:immunology; D001792:Blood Platelets / Q000276:immunology*; D004837:Epinephrine / Q000494:pharmacology; D006493:Heparin / Q000009:adverse effects* / Q000494:pharmacology; D006801:Humans; D010972:Platelet Activating Factor; D010974:Platelet Aggregation / Q000187:drug effects*; D013921:Thrombocytopenia / Q000097:blood / Q000209:etiology*
D001779:Blood Coagulation Factors; D010972:Platelet Activating Factor; D006493:Heparin; D004837:Epinephrine