title: Anti-PF4/heparin antibodies associated with repeated hemofiltration-filter clotting: a retrospective study.
abstract: BACKGROUND
  Heparin-induced thrombocytopenia is an immune-mediated adverse drug reaction that is associated with a procoagulant state and both arterial and venous thrombosis. After observing two cases of repeated hemofiltration-filter clotting associated with high anti-PF4/heparin antibody concentrations, we systematically measured the anti-PF4/heparin antibody concentration in all cases of unexpected and repeated hemofiltration-filter clotting during continuous veno-venous hemofiltration (CVVH). The aim of this study was to identify factors associated with positive anti-PF4/heparin antibody in the case of repeated hemofiltration-filter clotting.
  
  
  METHODS
  We reviewed the charts of all patients who had an anti-PF4/heparin antibody assay performed for repeated hemofiltration-filter clotting between November 2004 and May 2006 in our surgical intensive care unit. We used an enzyme-linked immunoabsorbent assay (heparin-platelet factor 4-induced antibody) with an optical density (OD) of greater than 1 IU considered positive.
  
  
  RESULTS
  During the study period, anti-PF4/heparin antibody assay was performed in 28 out of 87 patients receiving CVVH. Seven patients were positive for anti-PF4/heparin antibodies (OD 2.00 [1.36 to 2.22] IU) and 21 were antibody-negative (OD 0.20 [0.10 to 0.32] IU). Baseline characteristics, platelet counts, and activated partial thromboplastin time ratios were not different between the two groups. CVVH duration was significantly decreased in antibody-positive patients (5.0 [2.5 to 7.5] versus 12.0 [7.5 to 24.0] hours; P = 0.007) as was CVVH efficiency (urea reduction ratio 17% [10% to 37%] versus 44% [30% to 52%]; P = 0.04) on heparin infusion. Anti-PF4/heparin antibody concentration was inversely correlated with CVVH duration. The receiver operating characteristic curve showed that a 6-hour cutoff was the best CVVH session duration to predict a positive antibody test (sensitivity 71%, specificity 85%, and area under the curve 0.83). CVVH duration (32 [22 to 37] hours; P < 0.05) and urea reduction (55% [36% to 68%]; P < 0.03) were restored by danaparoid sodium infusion.
  
  
  CONCLUSIONS
  Repeated hemofiltration-filter clotting in less than 6 hours was often associated with the presence of anti-PF4/heparin antibodies, regardless of the platelet count. In antibody-positive patients, replacement of heparin by danaparoid sodium allowed the restoration of CVVH duration and efficiency.
authors.affiliation: Département d'Anesthésie - Réanimation Chirurgicale, APHP, CHU Bichat-Claude Bernard, Université Paris 7, Paris, France. sigismond@lasocki.com
authors.forename: Sigismond
authors.initials: S
authors.lastname: Lasocki
authors.forename: Pascale
authors.initials: P
authors.lastname: Piednoir
authors.forename: Nadine
authors.initials: N
authors.lastname: Ajzenberg
authors.forename: Arnaud
authors.initials: A
authors.lastname: Geffroy
authors.forename: Abdel
authors.initials: A
authors.lastname: Benbara
authors.forename: Philippe
authors.initials: P
authors.lastname: Montravers
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage; D001323:Autoantibodies / Q000097:blood*; D005260:Female; D006440:Hemofiltration / Q000295:instrumentation*; D006493:Heparin / Q000008:administration & dosage / Q000276:immunology*; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation; D010978:Platelet Factor 4 / Q000276:immunology*; D012189:Retrospective Studies; D013927:Thrombosis / Q000276:immunology*
chemical_list: D000925:Anticoagulants; D001323:Autoantibodies; D010978:Platelet Factor 4; D006493:Heparin