PMID- 23216710
OWN - NLM
STAT- MEDLINE
DCOM- 20130822
LR  - 20230829
IS  - 1538-7836 (Electronic)
IS  - 1538-7836 (Linking)
VI  - 11
IP  - 2
DP  - 2013 Feb
TI  - Anti-PF4/heparin antibodies and venous graft occlusion in postcoronary artery 
      bypass surgery patients randomized to postoperative unfractionated heparin or 
      fondaparinux thromboprophylaxis.
PG  - 253-60
LID - 10.1111/jth.12098 [doi]
AB  - BACKGROUND: Anti-PF4/heparin antibodies are frequently generated after coronary 
      artery bypass grafting (CABG) surgery, with platelet-activating IgG implicated in 
      heparin-induced thrombocytopenia (HIT). It is controversial whether 
      non-platelet-activating antibodies are associated with thrombosis. OBJECTIVES: To 
      determine in post-CABG patients whether thromboprophylaxis using fondaparinux vs. 
      unfractionated heparin (UFH) reduces the frequency of anti-PF4/heparin 
      antibodies, and whether anti-PF4/heparin antibodies are associated with early 
      graft occlusion. METHODS/PATIENTS: In a pre-planned secondary analysis of a 
      randomized control trial (RCT) comparing fondaparinux vs. UFH thromboprophylaxis 
      post-CABG, we determined the frequency of anti-PF4/heparin antibody formation by 
      solid-phase enzyme-immunoassay (EIA) and of platelet-activating antibodies by 
      serotonin-release assay (SRA); the SRA and fluid-phase EIA were used to assess 
      fondaparinux cross-reactivity. We also examined whether anti-PF4/heparin 
      antibodies were associated with early arterial or venous graft occlusion (6-week 
      CT angiography). RESULTS: We found no significant difference in the frequency of 
      antibody formation between patients who received fondaparinux vs. UFH (65.3% vs. 
      46.0%; P = 0.069), and no significant fondaparinux cross-reactivity. Venous graft 
      occlusion(s) occurred in 6/26 patients who formed 'strong' IgG antibodies (>/= 1.0 
      optical density [OD] units and >/= 2x baseline) vs. 3/66 who did not (P = 0.0139). 
      In both unadjusted and adjusted analyses, strong postoperative (but not 
      pre-operative) anti-PF4/heparin IgG responses were associated with a markedly 
      increased risk of early venous (but not arterial) graft occlusion (adjusted OR, 
      9.25 [95% CI, 1.73, 49.43]; P = 0.0093); notably, none of the three SRA-positive 
      patients developed a venous graft occlusion. CONCLUSIONS: Fondaparinux vs. UFH 
      thromboprophylaxis postCABG does not reduce anti-PF4/heparin antibody formation. 
      Non-platelet-activating anti-PF4/heparin IgG antibodies generated post 
      operatively are associated with early venous graft occlusion.
CI  - (c) 2012 International Society on Thrombosis and Haemostasis.
FAU - Warkentin, T E
AU  - Warkentin TE
AD  - Department of Pathology and Molecular Medicine, McMaster University, Hamilton, 
      ON, Canada. twarken@mcmaster.ca
FAU - Sheppard, J I
AU  - Sheppard JI
FAU - Sun, J C J
AU  - Sun JC
FAU - Jung, H
AU  - Jung H
FAU - Eikelboom, J W
AU  - Eikelboom JW
LA  - eng
SI  - ClinicalTrials.gov/NCT00474591
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Thromb Haemost
JT  - Journal of thrombosis and haemostasis : JTH
JID - 101170508
RN  - 0 (Antibodies)
RN  - 0 (Anticoagulants)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Polysaccharides)
RN  - 37270-94-3 (Platelet Factor 4)
RN  - 9005-49-6 (Heparin)
RN  - J177FOW5JL (Fondaparinux)
SB  - IM
MH  - Antibodies/*blood
MH  - Anticoagulants/adverse effects/*immunology
MH  - Coronary Artery Bypass/*adverse effects
MH  - Cross Reactions
MH  - Fondaparinux
MH  - Graft Occlusion, Vascular/*etiology/immunology
MH  - Heparin/adverse effects/*immunology
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - Immunoglobulin G/*blood
MH  - Logistic Models
MH  - Odds Ratio
MH  - Ontario
MH  - Pilot Projects
MH  - Platelet Factor 4/*immunology
MH  - Polysaccharides/adverse effects/*immunology
MH  - Risk Assessment
MH  - Risk Factors
MH  - Thrombocytopenia/etiology/immunology
MH  - Time Factors
MH  - Treatment Outcome
EDAT- 2012/12/12 06:00
MHDA- 2013/08/24 06:00
CRDT- 2012/12/11 06:00
PHST- 2012/08/29 00:00 [received]
PHST- 2012/11/17 00:00 [accepted]
PHST- 2012/12/11 06:00 [entrez]
PHST- 2012/12/12 06:00 [pubmed]
PHST- 2013/08/24 06:00 [medline]
AID - S1538-7836(22)11133-5 [pii]
AID - 10.1111/jth.12098 [doi]
PST - ppublish
SO  - J Thromb Haemost. 2013 Feb;11(2):253-60. doi: 10.1111/jth.12098.