PMID- 23722881
OWN - NLM
STAT- MEDLINE
DCOM- 20140107
LR  - 20170527
IS  - 1931-3543 (Electronic)
IS  - 0012-3692 (Linking)
VI  - 144
IP  - 3
DP  - 2013 Sep
TI  - Heparin-induced thrombocytopenia in medical surgical critical illness.
PG  - 848-858
LID - S0012-3692(13)60599-1 [pii]
LID - 10.1378/chest.13-0057 [doi]
AB  - 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 < .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.
FAU - Warkentin, Theodore E
AU  - Warkentin TE
AD  - Department of Pathology and Molecular Medicine, McMaster University, Hamilton, 
      ON, Canada. Electronic address: twarken@mcmaster.ca.
FAU - Sheppard, Jo-Ann I
AU  - Sheppard JI
AD  - Department of Pathology and Molecular Medicine, McMaster University, Hamilton, 
      ON, Canada.
FAU - Heels-Ansdell, Diane
AU  - Heels-Ansdell D
AD  - Department of Clinical Epidemiology and Biostatistics, McMaster University, 
      Hamilton, ON, Canada.
FAU - Marshall, John C
AU  - Marshall JC
AD  - St. Michael's Hospital and the University of Toronto, Toronto, ON, Canada.
FAU - McIntyre, Lauralyn
AU  - McIntyre L
AD  - Ottawa Hospital General Campus and University of Ottawa, Ottawa, ON, Canada.
FAU - Rocha, Marcelo G
AU  - Rocha MG
AD  - Pavilhao Pereira Filho, Santa Casa de Porto Alegre, Brazil.
FAU - Mehta, Sangeeta
AU  - Mehta S
AD  - Mount Sinai Hospital and the University of Toronto, Toronto, ON, Canada.
FAU - Davies, Andrew R
AU  - Davies AR
AD  - Alfred Hospital, Melbourne, Melbourne, VIC, Australia.
FAU - Bersten, Andrew D
AU  - Bersten AD
AD  - Flinders Medical Centre and Flinders University, Adelaide, SA, Australia.
FAU - Crozier, Tim M
AU  - Crozier TM
AD  - Monash Medical Centre, Melbourne, VIC, Australia.
FAU - Ernest, David
AU  - Ernest D
AD  - Box Hill Hospital and Monash University, Melbourne, VIC, Australia.
FAU - Vlahakis, Nicholas E
AU  - Vlahakis NE
AD  - Mayo Clinic, Rochester, MN.
FAU - Hall, Richard I
AU  - Hall RI
AD  - Capital Health Queen Elizabeth II Health Science Center and Dalhousie University, 
      Halifax, NS, Canada.
FAU - Wood, Gordon G
AU  - Wood GG
AD  - Vancouver Island Health Authority, Victoria, BC, Canada.
FAU - Poirier, Germain
AU  - Poirier G
AD  - Charles LeMoyne Hospital, Longueuil, QC, Canada.
FAU - Crowther, Mark A
AU  - Crowther MA
AD  - St. Joseph's Healthcare, Hamilton, ON, Canada.
FAU - Cook, Deborah J
AU  - Cook DJ
AD  - St. Joseph's Healthcare, Hamilton, ON, Canada.
CN  - Canadian Critical Care Trials Group and the Australian and New Zealand Intensive 
      Care Society Clinical Trials Group
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Chest
JT  - Chest
JID - 0231335
RN  - 0 (Anticoagulants)
RN  - S79O08V79F (Dalteparin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Anticoagulants/adverse effects/therapeutic use
MH  - Blood Platelets/*drug effects
MH  - Critical Illness/*therapy
MH  - Dalteparin/*adverse effects/therapeutic use
MH  - Dose-Response Relationship, Drug
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Humans
MH  - Injections, Intravenous
MH  - Male
MH  - Middle Aged
MH  - Prognosis
MH  - Thrombocytopenia/*chemically induced
MH  - Young Adult
EDAT- 2013/06/01 06:00
MHDA- 2014/01/08 06:00
CRDT- 2013/06/01 06:00
PHST- 2013/06/01 06:00 [entrez]
PHST- 2013/06/01 06:00 [pubmed]
PHST- 2014/01/08 06:00 [medline]
AID - S0012-3692(13)60599-1 [pii]
AID - 10.1378/chest.13-0057 [doi]
PST - ppublish
SO  - Chest. 2013 Sep;144(3):848-858. doi: 10.1378/chest.13-0057.