title: Incidence of antibodies to protamine sulfate/heparin complexes incardiac surgery patients and impact on platelet activation and clinical outcome.
abstract: A new ELISA (Zymutest HIA®), based on incubation of diluted plasma with protamine/heparin (PRT/H) complexes without and with platelet factor 4 (PF4) provided by a platelet lysate, was used to detect heparin-dependent antibodies in a cohort of 232 cardiac surgery (CS) patients and in 47 patients with heparin-induced thrombocytopenia (HIT). Significant binding of IgG/A/M to PRT/H complexes was demonstrated in 59 CS patients (25.4%), with similar absorbances whether platelet lysate was added to the plasma or not, and significant reactivity to PF4/H in 29 of them. Antibodies to PRT or heparin alone were present in 15 and two of these patients, respectively. Importantly, antibodies to PRT/H were detected in only three of the 47 HIT patients, who had also undergone recent CS. The Zymutest HIA® was positive in another 41 CS patients (17%), but only or mainly when their plasma was tested with platelet lysate, with significant levels of antibodies to PF4/H in 40 of them without detectable reactivity to PRT or heparin alone. Slight antibody binding to PRT/H complexes was also measured in six of these 41 patients. Therefore, a total of 35 CS patients exhibited dual antibody reactivity towards PRT/H and PF4/H complexes. Serotonin release assay performed with PRT alone was positive in 17 CS patients with antibodies to PRT/H, but all had normal platelet count evolution without thrombosis postoperatively. In conclusion, antibodies to PRT/H are frequently present in CS patients postoperatively (25.4%), and can activate platelets in vitro, but their clinical impact remains questionable.
authors: Department of Hematology-Hemostasis, Trousseau Hospital, 37044 Tours Cedex, France.
authors: Claire
authors: C
authors: Pouplard
authors: Dorothée
authors: D
authors: Leroux
authors: Jérome
authors: J
authors: Rollin
authors: Jean
authors: J
authors: Amiral
authors: Marc-Antoine
authors: MA
authors: May
authors: Yves
authors: Y
authors: Gruel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000276:immunology*; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D003324:Coronary Artery Disease / Q000150:complications / Q000601:surgery; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006493:Heparin / Q000009:adverse effects / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000737:chemistry; D015539:Platelet Activation / Q000187:drug effects*; D011479:Protamines / Q000737:chemistry* / Q000276:immunology; D012701:Serotonin / Q000378:metabolism; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000276:immunology; D013927:Thrombosis / Q000276:immunology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000906:Antibodies; D010455:Peptides; D011479:Protamines; D012701:Serotonin; D006493:Heparin