Abstract |
Heparin induced thrombocytopenia (HIT) is characterized by the formation of antibodies that activate normal donor platelets in vitro in the presence of heparin. We asked whether the commonly observed donor-specific variation in the platelet aggregation response to HIT antibodies is influenced by the density of Fc gamma RII on platelets or by the Arg/His 131 allelic polymorphism of platelet Fc gamma RII. We found that platelets with His/His 131 Fc gamma RII phenotype were unresponsive to HIT antibody (0/9) whereas platelets with the Arg/Arg 131 phenotype responded well (7/9). His/His 131 platelets were largely unresponsive also to a murine IgG1 antiplatelet monoclonal antibody (UR1) known to activate platelets by Fc gamma RII clustering. We then determined the frequency distribution of Fc gamma RIIa Arg/His 131 phenotypes on a series of 200 patients evaluated for HIT and 100 non-thrombocytopenic hospitalized patients. The frequency of the His/His 131 phenotype was significantly increased (34.4%) in the 96 thrombocytopenic patients with HIT antibody compared to the 104 thrombocytopenic patients without HIT antibody and the 100 non-thrombocytopenic patients (approximately 19%). Thus, the Fc gamma RII phenotype regulates the in vitro activation response of normal platelets to HIT antibody and is a risk factor for the thrombocytopenia of HIT.
|
Authors | J T Brandt, C E Isenhart, J M Osborne, A Ahmed, C L Anderson |
Journal | Thrombosis and haemostasis
(Thromb Haemost)
Vol. 74
Issue 6
Pg. 1564-72
(Dec 1995)
ISSN: 0340-6245 [Print] Germany |
PMID | 8772238
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
|
Chemical References |
- Antibodies
- Antigens, CD
- Fc gamma receptor IIA
- Receptors, IgG
- Histidine
- Heparin
- Arginine
|
Topics |
- Antibodies
(blood)
- Antigens, CD
(genetics, metabolism)
- Arginine
- Base Sequence
- Genotype
- Heparin
(adverse effects)
- Histidine
- Humans
- Molecular Sequence Data
- Phenotype
- Platelet Activation
(immunology)
- Platelet Aggregation
(drug effects, genetics)
- Receptors, IgG
(genetics, metabolism)
- Thrombocytopenia
(blood, chemically induced, genetics)
|