title: Platelet-activating protamine-heparin-antibodies lead to higher protamine demand in patients undergoing cardiac surgery.
abstract: OBJECTIVE
  Platelet-activating antibodies against protamine-heparin-complexes were described in patients undergoing cardiac surgery, but their clinical consequences remain unclear. This prospective single-center observational study aimed to describe the prevalence and clinical consequences of protamine-heparin-complex antibodies in patients undergoing cardiac surgery with cardiopulmonary bypass.
  
  
  METHODS
  A total of 200 patients undergoing cardiac surgery with cardiopulmonary bypass were included. Blood samples were collected preoperatively and 1 hour, 24 hours, and 7 days after weaning from cardiopulmonary bypass. All sera were tested for the presence of protamine-heparin-complex antibodies using a modified heparin-induced platelet-activation assay. Specific Fcγ receptor IIa-dependent platelet activation was confirmed by repeated testing in the presence of the Fcγ receptor IIa-blocking antibody IV.3.
  
  
  RESULTS
  Samples from 185 patients were obtained, of whom 24 patients (13%) were positive for protamine-heparin-complex antibodies preoperatively. In all positive samples, functional reactivity was reversible in the presence of IV.3. Although patients with a preoperative presence of protamine-heparin-complex antibodies were significantly older compared with patients negative for protamine-heparin-complex antibodies (73 ± 9.8 years vs 68 ± 10 years, P = .037), no other potential risk factors were identified at 1 day before operation. Patients with protamine-heparin-complex antibodies required significantly more protamine to neutralize heparin (47.66 mg vs 41.67 mg, P = .027). Protamine-heparin-complex antibodies have no significant influence on perioperative platelet numbers, bleeding complications, transfusion requirement, thromboembolic events, major cardiovascular and cerebrovascular events, inflammation parameters, or kidney function.
  
  
  CONCLUSIONS
  Protamine-heparin-complex antibodies occur frequently in patients undergoing cardiac surgery on cardiopulmonary bypass, resulting in specific platelet activation in vitro. Protamine-heparin-complex antibodies are associated with increased protamine requirement after cardiopulmonary bypass and possibly slower recovery of platelet numbers.
authors: Department of Adult and Pediatric Cardiovascular Surgery, University Hospital Giessen, Giessen, Germany. Electronic address: Philippe.grieshaber@chiru.med.uni-giessen.de.
authors: Philippe
authors: P
authors: Grieshaber
authors: Department of Transfusion Medicine, Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany.
authors: Tamam
authors: T
authors: Bakchoul
authors: Department of Internal Medicine, German Center for Lung Research, Justus Liebig University, Giessen, Germany.
authors: Jochen
authors: J
authors: Wilhelm
authors: Department of Adult and Pediatric Cardiovascular Surgery, University Hospital Giessen, Giessen, Germany.
authors: Alexander
authors: A
authors: Wagner
authors: Department of Anaesthesiology and Intensive Care Medicine University Hospital Giessen, Giessen, Germany.
authors: Matthias
authors: M
authors: Wollbrück
authors: Department of Adult and Pediatric Cardiovascular Surgery, University Hospital Giessen, Giessen, Germany.
authors: Andreas
authors: A
authors: Böning
authors: Institute for Clinical Immunology und Transfusion Medicine, Justus Liebig University Giessen, Giessen, Germany.
authors: Ulrich
authors: U
authors: Sachs
mesh_terms: D000368:Aged; D000906:Antibodies / Q000097:blood*; D000925:Anticoagulants / Q000276:immunology*; D002315:Cardiopulmonary Bypass; D005260:Female; D006493:Heparin / Q000276:immunology*; D006494:Heparin Antagonists / Q000276:immunology* / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D015539:Platelet Activation / Q000276:immunology*; D011446:Prospective Studies; D011479:Protamines / Q000276:immunology* / Q000627:therapeutic use*
chemical_list: D000906:Antibodies; D000925:Anticoagulants; D006494:Heparin Antagonists; D011479:Protamines; D006493:Heparin
keywords: cardiopulmonary bypass; drug-dependent antibodies; platelet activation; protamine; thrombocytopenia