PMID- 16109780
OWN - NLM
STAT- MEDLINE
DCOM- 20060118
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 106
IP  - 12
DP  - 2005 Dec 1
TI  - Anti-platelet factor 4/heparin antibodies in orthopedic surgery patients 
      receiving antithrombotic prophylaxis with fondaparinux or enoxaparin.
PG  - 3791-6
AB  - Heparin-induced thrombocytopenia (HIT) is caused by platelet-activating IgG 
      antibodies that recognize platelet factor 4 (PF4) bound to heparin. 
      Immunogenicity of heparins differs in that unfractionated heparin (UFH) induces 
      more anti-PF4/heparin antibodies than low-molecular-weight heparin (LMWH) and UFH 
      also causes more HIT. Fondaparinux, a synthetic anticoagulant modeled after the 
      antithrombin-binding pentasaccharide, is believed to be nonimmunogenic. We tested 
      2726 patients for anti-PF4/heparin antibodies after they were randomized to 
      receive antithrombotic prophylaxis with fondaparinux or LMWH (enoxaparin) 
      following hip or knee surgery. We also evaluated in vitro cross-reactivity of the 
      IgG antibodies generated against PF4 in the presence of UFH, LMWH, danaparoid, or 
      fondaparinux. We found that anti-PF4/heparin antibodies were generated at similar 
      frequencies in patients treated with fondaparinux or enoxaparin. Although 
      antibodies reacted equally well in vitro against PF4/UFH and PF4/LMWH, and 
      sometimes weakly against PF4/danaparoid, none reacted against PF4/fondaparinux, 
      including even those sera obtained from patients who formed antibodies during 
      fondaparinux treatment. At high concentrations, however, fondaparinux inhibited 
      binding of HIT antibodies to PF4/polysaccharide, indicating that PF4/fondaparinux 
      interactions occur. No patient developed HIT. We conclude that despite similar 
      immunogenicity of fondaparinux and LMWH, PF4/fondaparinux, but not PF4/LMWH, is 
      recognized poorly by the antibodies generated, suggesting that the risk of HIT 
      with fondaparinux likely is very low.
FAU - Warkentin, Theodore E
AU  - Warkentin TE
AD  - Department of Pathology and Molecular Medicine, McMaster University, Hamilton, 
      ON, Canada. twarken@mcmaster.ca
FAU - Cook, Richard J
AU  - Cook RJ
FAU - Marder, Victor J
AU  - Marder VJ
FAU - Sheppard, Jo-Ann I
AU  - Sheppard JA
FAU - Moore, Jane C
AU  - Moore JC
FAU - Eriksson, Bengt I
AU  - Eriksson BI
FAU - Greinacher, Andreas
AU  - Greinacher A
FAU - Kelton, John G
AU  - Kelton JG
LA  - eng
GR  - R0-1 HL 074051/HL/NHLBI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20050818
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Anticoagulants)
RN  - 0 (Enoxaparin)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Polysaccharides)
RN  - 37270-94-3 (Platelet Factor 4)
RN  - J177FOW5JL (Fondaparinux)
SB  - IM
MH  - Anticoagulants/*immunology/therapeutic use
MH  - Cross Reactions
MH  - Double-Blind Method
MH  - Enoxaparin/*therapeutic use
MH  - Fondaparinux
MH  - Hip/surgery
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - Immunoglobulin G/blood
MH  - Knee/surgery
MH  - Orthopedic Procedures/adverse effects
MH  - Platelet Factor 4/*immunology
MH  - Polysaccharides/*immunology/therapeutic use
MH  - Thrombocytopenia/chemically induced
MH  - Venous Thrombosis/etiology/*prevention & control
PMC - PMC1895104
EDAT- 2005/08/20 09:00
MHDA- 2006/01/19 09:00
PMCR- 2006/12/01
CRDT- 2005/08/20 09:00
PHST- 2005/08/20 09:00 [pubmed]
PHST- 2006/01/19 09:00 [medline]
PHST- 2005/08/20 09:00 [entrez]
PHST- 2006/12/01 00:00 [pmc-release]
AID - S0006-4971(20)66912-9 [pii]
AID - 3791 [pii]
AID - 10.1182/blood-2005-05-1938 [doi]
PST - ppublish
SO  - Blood. 2005 Dec 1;106(12):3791-6. doi: 10.1182/blood-2005-05-1938. Epub 2005 Aug 
      18.