|
|
 Previous Article | Table of Contents | Next Article 
Fc gamma RIIA H/R 131 polymorphism, subclass-specific IgG anti-
heparin/platelet factor 4 antibodies and clinical course in patients with
heparin-induced thrombocytopenia and thrombosis
G Arepally, SE McKenzie, XM Jiang, M Poncz and DB Cines
Department of Medicine, University of Pennsylvania, Philadelphia 19104,
USA.
The explanation why only a subset of patients with heparin-induced
thrombocytopenia (HIT) develop clinically apparent thromboses (HITT)
remains uncertain. It has been proposed that platelet activation induced by
cross-linking of Fc gamma RIIA by anti-heparin/platelet factor 4 (PF4)
antibodies is central to the pathogenesis of thrombosis. The observation
that a common functional polymorphism of Fc gamma RIIA, involving either an
arginine (R) or histidine (H) at amino acid 131, may underlie disease
susceptibility prompted us to investigate the prevalence of receptor
isoforms in patients with HIT and HITT. Furthermore, because these isoforms
reportedly differ in their avidity for immune complexes containing human
IgG2, we also analyzed sera from patients with HIT and HITT for the
prevalence of various subclass- specific IgG anti-heparin/PF4 antibodies.
No difference in the allele frequency of Fc gamma RIIA-H131 or R131 was
identified among 13 patients with HIT or 23 with HITT compared with 102
controls (chi 2 = 1.21, P = .8). Furthermore, although most patients had
IgG2 antibodies (62%), IgG, was the predominant subclass in 30 of the 34
patients with IgG anti-heparin/PF4 antibodies and in 12 was the exclusive
subclass found. Also, there was no association between the concordance of
IgG2 anti-heparin/ PF4 antibodies and the expression of Fc gamma RIIA-H131
in patients with HITT compared with patients with thrombocytopenia alone.
These results make it unlikely that the Fc gamma RIIA-H131 isoform or IgG2
anti-heparin/PF4 antibodies are required to develop HITT, suggesting that
factors in addition to cross-linking of Fc gamma RIIA receptors contribute
to the pathogenesis of thrombosis in patients with heparin-dependent
antiplatelet: antibodies.
Volume 89,
Issue 2,
pp. 370-375,
01/15/1997
Copyright © 1997 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
S. Suvarna, L. Rauova, E. K. E. McCracken, C. M. Goss, B. S. Sachais, S. E. McKenzie, M. P. Reilly, M. D. Gunn, D. B. Cines, M. Poncz, et al.
PF4/heparin complexes are T cell-dependent antigens
Blood,
August 1, 2005;
106(3):
929 - 931.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. G. Kelton
The Pathophysiology of Heparin-Induced Thrombocytopenia: Biological Basis for Treatment
Chest,
February 1, 2005;
127(2_suppl):
9S - 20S.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. A. Fox, S. K. Shernan, and S. C. Body
Predictive Genomics of Adverse Events After Cardiac Surgery
Seminars in Cardiothoracic and Vascular Anesthesia,
December 1, 2004;
8(4):
297 - 315.
[Abstract]
[PDF]
|
|
|
|
|
|
|
E. Pravinkumar and N. R. Webster
HIT/HITT and alternative anticoagulation: current concepts
Br. J. Anaesth.,
May 1, 2003;
90(5):
676 - 685.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Q. Li, W. Liu, K. S. Park, B. S. Sachais, G. M. Arepally, D. B. Cines, and M. Poncz
Defining a second epitope for heparin-induced thrombocytopenia/thrombosis antibodies using KKO, a murine HIT-like monoclonal antibody
Blood,
February 15, 2002;
99(4):
1230 - 1236.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. E. Warkentin and J. G. Kelton
Temporal Aspects of Heparin-Induced Thrombocytopenia
N. Engl. J. Med.,
April 26, 2001;
344(17):
1286 - 1292.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. M. Taylor, M. P. Reilly, A. D. Schreiber, P. Chien, J. R. Tuckosh, and S. E. McKenzie
Thrombosis and shock induced by activating antiplatelet antibodies in human Fcgamma RIIA transgenic mice: the interplay among antibody, spleen, and Fc receptor
Blood,
December 15, 2000;
96(13):
4254 - 4260.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Pohl, U. Harbrecht, A. Greinacher, I. Theuerkauf, R. Biniek, P. Hanfland, and T. Klockgether
Neurologic complications in immune-mediated heparin-induced thrombocytopenia
Neurology,
March 28, 2000;
54(6):
1240 - 1245.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. M. Arepally, S. Kamei, K. S. Park, K. Kamei, Z. Q. Li, W. Liu, D. L. Siegel, W. Kisiel, D. B. Cines, and M. Poncz
Characterization of a murine monoclonal antibody that mimics heparin-induced thrombocytopenia antibodies
Blood,
March 1, 2000;
95(5):
1533 - 1540.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Lehrnbecher, C. B. Foster, S. Zhu, S. F. Leitman, L. R. Goldin, K. Huppi, and S. J. Chanock
Variant Genotypes of the Low-Affinity Fcgamma Receptors in Two Control Populations and a Review of Low-Affinity Fcgamma Receptor Polymorphisms in Control and Disease Populations
Blood,
December 15, 1999;
94(12):
4220 - 4232.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Pouplard, M.-A. May, S. Iochmann, J. Amiral, A.-M. Vissac, M. Marchand, and Y. Gruel
Antibodies to Platelet Factor 4–Heparin After Cardiopulmonary Bypass in Patients Anticoagulated With Unfractionated Heparin or a Low-Molecular-Weight Heparin : Clinical Implications for Heparin-Induced Thrombocytopenia
Circulation,
May 18, 1999;
99(19):
2530 - 2536.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. E. McKenzie, S. M. Taylor, P. Malladi, H. Yuhan, D. L. Cassel, P. Chien, E. Schwartz, A. D. Schreiber, S. Surrey, and M. P. Reilly
The Role of the Human Fc Receptor Fc{gamma}RIIA in the Immune Clearance of Platelets: A Transgenic Mouse Model
J. Immunol.,
April 1, 1999;
162(7):
4311 - 4318.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. E. Carlsson, S. Santoso, G. Baurichter, H. Kroll, S. Papenberg, P. Eichler, N. A.C. Westerdaal, V. Kiefel, J. G.J. van de Winkel, and A. Greinacher
Heparin-Induced Thrombocytopenia: New Insights Into the Impact of the Fcgamma RIIa-R-H131 Polymorphism
Blood,
September 1, 1998;
92(5):
1526 - 1531.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Polgar, P. Eichler, A. Greinacher, and K. J. Clemetson
Adenosine Diphosphate (ADP) and ADP Receptor Play a Major Role in Platelet Activation/Aggregation Induced by Sera From Heparin-Induced Thrombocytopenia Patients
Blood,
January 15, 1998;
91(2):
549 - 554.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
