title: Heparin-induced thrombocytopenia in medical surgical critical illness.
abstract: BACKGROUND
  In a recent multicenter randomized trial comparing unfractionated heparin (UFH) with low-molecular-weight heparin (dalteparin) for thromboprophylaxis in 3,746 critically ill patients, 17 patients (0.5%) developed heparin-induced thrombocytopenia (HIT) based on serotonin-release assay-positive (SRA+) status. A trend to a lower frequency of HIT with dalteparin vs UFH was observed in the intention-to-treat analysis (five vs 12 patients, P = .14), which was statistically significant (three vs 12 patients, P = .046) in a prespecified per-protocol analysis that excluded patients with DVT at study entry. We sought to characterize HIT outcomes and to determine how dalteparin thromboprophylaxis may reduce HIT frequency in patients in the ICU.
  
  
  METHODS
  In 17 patients with HIT, we analyzed platelet counts and thrombotic events in relation to the study drug and other open-label heparin, to determine whether the study drug plausibly explained seroconversion to SRA+ status and/or breakthrough of thrombocytopenia/thrombosis. We also compared antibody frequencies (dalteparin vs UFH) in 409 patients serologically investigated for HIT.
  
  
  RESULTS
  HIT-associated thrombosis occurred in 10 of 17 patients (58.8%) (8:1:1 venous:arterial:both). Dalteparin was associated with fewer study drug-attributable HIT-related events (P = .020), including less seroconversion (P = .058) and less breakthrough of thrombocytopenia/thrombosis (P = .032). Antiplatelet factor 4/heparin IgG antibodies by enzyme-linked immunosorbent assay were less frequent among patients receiving dalteparin vs UFH (13.5% vs 27.3%, P &lt; .001). One patient with HIT-associated DVT died after UFH bolus (anaphylactoid reaction), whereas platelet counts recovered in two others with HIT-associated VTE despite continuation of therapeutic-dose UFH.
  
  
  CONCLUSIONS
  The lower risk of HIT in patients in the ICU receiving dalteparin appears related to both decreased antibody formation and decreased clinical breakthrough of HIT among patients forming antibodies.
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada. Electronic address: twarken@mcmaster.ca.
authors.forename: Theodore E
authors.initials: TE
authors.lastname: Warkentin
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: Jo-Ann I
authors.initials: JI
authors.lastname: Sheppard
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.
authors.forename: Diane
authors.initials: D
authors.lastname: Heels-Ansdell
authors.affiliation: St. Michael's Hospital and the University of Toronto, Toronto, ON, Canada.
authors.forename: John C
authors.initials: JC
authors.lastname: Marshall
authors.affiliation: Ottawa Hospital General Campus and University of Ottawa, Ottawa, ON, Canada.
authors.forename: Lauralyn
authors.initials: L
authors.lastname: McIntyre
authors.affiliation: Pavilhão Pereira Filho, Santa Casa de Porto Alegre, Brazil.
authors.forename: Marcelo G
authors.initials: MG
authors.lastname: Rocha
authors.affiliation: Mount Sinai Hospital and the University of Toronto, Toronto, ON, Canada.
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Mehta
authors.affiliation: Alfred Hospital, Melbourne, Melbourne, VIC, Australia.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Davies
authors.affiliation: Flinders Medical Centre and Flinders University, Adelaide, SA, Australia.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Bersten
authors.affiliation: Monash Medical Centre, Melbourne, VIC, Australia.
authors.forename: Tim M
authors.initials: TM
authors.lastname: Crozier
authors.affiliation: Box Hill Hospital and Monash University, Melbourne, VIC, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Ernest
authors.affiliation: Mayo Clinic, Rochester, MN.
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Vlahakis
authors.affiliation: Capital Health Queen Elizabeth II Health Science Center and Dalhousie University, Halifax, NS, Canada.
authors.forename: Richard I
authors.initials: RI
authors.lastname: Hall
authors.affiliation: Vancouver Island Health Authority, Victoria, BC, Canada.
authors.forename: Gordon G
authors.initials: GG
authors.lastname: Wood
authors.affiliation: Charles LeMoyne Hospital, Longueuil, QC, Canada.
authors.forename: Germain
authors.initials: G
authors.lastname: Poirier
authors.affiliation: St. Joseph's Healthcare, Hamilton, ON, Canada.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Crowther
authors.affiliation: St. Joseph's Healthcare, Hamilton, ON, Canada.
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Cook
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects*; D016638:Critical Illness / Q000628:therapy*; D017985:Dalteparin / Q000009:adverse effects* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D013921:Thrombocytopenia / Q000139:chemically induced*; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D017985:Dalteparin