title: Incidence and clinical relevance of anti-platelet factor 4/heparin antibodies before cardiac surgery.
abstract: BACKGROUND
  Heparin-induced thrombocytopenia (HIT) is caused by anti-platelet factor 4/heparin (PF4/H) immunoglobulin (Ig) G antibodies, which activate platelets. In some patients, anti-PF4/H antibodies are already detectable before cardiac surgery. Whether preoperative presence of antibodies confers adverse prognosis and which particular antibody classes (IgG, IgA, IgM) might be implicated are unknown.
  
  
  METHODS
  We prospectively screened 591 patients undergoing cardiopulmonary bypass surgery for heparin-dependent antibodies by PF4/H immunoassay (separately for IgG, IgA, and IgM) and platelet activation test at preoperative baseline and at days 6 and 10. All patients received heparin or low-molecular-weight heparin postsurgery regardless of antibody status and were followed for postoperative complications, frequency of HIT, length of hospital stay, and 30-day mortality.
  
  
  RESULTS
  Anti-PF4/H antibodies of any class were detected at preoperative baseline in 128 (21.7%) of 591 patients: IgG n = 44 (7.4%), IgA n = 36 (6.1%), and IgM n = 79 (13.4%); some patients had >1 antibody class. Neither IgG nor IgA was a risk factor for any adverse outcome parameter. However, preoperative presence of IgM antibodies was associated with an increased risk for nonthromboembolic complications (all complications combined: hazard ratio 1.73, 95% CI 1.15-2.61) and a longer in-hospital stay (P = .02), but without evidence for increased risk of thrombotic complications or subsequent HIT.
  
  
  CONCLUSIONS
  Patients with preoperative anti-PF4/H antibodies of IgG and IgA class are not at increased risk for thrombotic or nonthrombotic adverse events, whereas those with baseline anti-PF4/H IgM had an increased risk of nonthrombotic adverse outcomes but not of subsequent HIT or thrombosis. Because IgM antibodies do not cause HIT, they could represent a surrogate marker for other heparin-independent risk factors.
authors.affiliation: Institut für Immunologie und Transfusionsmedizin, Ernst-Moritz-Arndt Universität, Greifswald, Germany. sixten.selleng@uni-greifswald.de
authors.forename: Sixten
authors.initials: S
authors.lastname: Selleng
authors.forename: Birgit
authors.initials: B
authors.lastname: Malowsky
authors.forename: Till
authors.initials: T
authors.lastname: Itterman
authors.forename: Jessica
authors.initials: J
authors.lastname: Bagemühl
authors.forename: Antje
authors.initials: A
authors.lastname: Wessel
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Wollert
authors.forename: Theodore E
authors.initials: TE
authors.lastname: Warkentin
authors.forename: Andreas
authors.initials: A
authors.lastname: Greinacher
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects / Q000276:immunology*; D006348:Cardiac Surgical Procedures; D005260:Female; D006493:Heparin / Q000009:adverse effects / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008297:Male; D010978:Platelet Factor 4 / Q000276:immunology*; D057234:Preoperative Period; D011446:Prospective Studies; D013921:Thrombocytopenia / Q000139:chemically induced / Q000175:diagnosis / Q000276:immunology
chemical_list: D000925:Anticoagulants; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D010978:Platelet Factor 4; D006493:Heparin