title: The occurrence of antibodies to heparin-platelet factor 4 in cardiac and thoracic surgical patients receiving desirudin or heparin for postoperative venous thrombosis prophylaxis.
abstract: BACKGROUND
  This randomized, exploratory study compared the incidence of heparin-dependent antibodies associated with subcutaneous (SC) desirudin or heparin given for deep-vein thrombosis prophylaxis following cardiac and thoracic surgery.
  
  
  METHODS
  Adult patients scheduled for elective cardiac or thoracic surgery received desirudin 15 mg SC twice daily or unfractionated heparin 5000 units SC thrice daily. Duration of thrombosis prophylaxis was determined by the treating physician. Primary outcome measure was the incidence of new antibody formation directed against platelet factor 4 (PF4)/heparin complex. Secondary outcomes included bleeding and thrombotic complications. Blood was tested for anti-PF4/heparin antibodies at baseline, after surgery prior to study drug administration, postdrug day (PDD) 2, PDD 7, and at 1 month. Doppler studies were done before discharge.
  
  
  RESULTS
  Of 120 patients, 61 received desirudin, 59 received heparin. New PF4/heparin antibodies occurred in 10.2% and 13.6% of desirudin- and heparin-treated patients, respectively. Among desirudin patients with no heparin exposure, none (0/36) developed PF4/heparin antibodies versus 17.1% with heparin exposure. Incidence of deep venous thrombosis was 4.9% and 3.4% in the desirudin and heparin groups, respectively. Two heparin-group patients developed pulmonary embolism. Two patients per group had bleeding events; no patients required re-exploration for bleeding complications. Median chest tube output was similar with desirudin (900 mL) and heparin (692 mL) as was blood transfusion requirements of more than 2 units (5/61, desirudin; 2/59 heparin).
  
  
  CONCLUSIONS
  The incidence of thrombotic events was low in both groups. There were no safety concerns, and desirudin was not associated with anti-PF4/heparin antibodies.
authors.affiliation: Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA. avidanm@msnotes.wustl.edu
authors.forename: Michael S
authors.initials: MS
authors.lastname: Avidan
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Smith
authors.forename: Lee P
authors.initials: LP
authors.lastname: Skrupky
authors.forename: Laureen
authors.initials: L
authors.lastname: Hill
authors.forename: Eric
authors.initials: E
authors.lastname: Jacobsohn
authors.forename: Beth
authors.initials: B
authors.lastname: Burnside
authors.forename: Heidi
authors.initials: H
authors.lastname: Tymkew
authors.forename: Charles
authors.initials: C
authors.lastname: Eby
authors.forename: Ralph
authors.initials: R
authors.lastname: Damiano
authors.forename: George J
authors.initials: GJ
authors.lastname: Despotis
mesh_terms: D000906:Antibodies / Q000097:blood* / Q000276:immunology; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use; D006348:Cardiac Surgical Procedures / Q000009:adverse effects / Q000379:methods; D005260:Female; D006493:Heparin / Q000276:immunology / Q000627:therapeutic use*; D006629:Hirudins / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time / Q000379:methods; D010978:Platelet Factor 4 / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology / Q000627:therapeutic use; D019616:Thoracic Surgical Procedures / Q000009:adverse effects / Q000379:methods; D020246:Venous Thrombosis / Q000188:drug therapy / Q000276:immunology* / Q000517:prevention & control*
chemical_list: D000906:Antibodies; D000925:Anticoagulants; D006629:Hirudins; D011994:Recombinant Proteins; D010978:Platelet Factor 4; D006493:Heparin; C060225:desirudin