Heparin-induced thrombocytopenia: new insights into the impact of the FcgammaRIIa-R-H131 polymorphism.
Heparin-induced thrombocytopenia (HIT), a severe complication of heparin treatment, can be associated with new thrombotic complications. HIT antibodies activate platelets via the platelet Fcgamma-receptor (FcgammaRIIa), which carries a functionally relevant polymorphism (FcgammaRIIa-R-H131). The effect of this polymorphism on the clinical manifestations of HIT is controversial. We determined prospectively the FcgammaRIIa-R-H131 genotypes in 389 HIT patients, in 351 patients with thrombocytopenia or thrombosis due to causes other than HIT and without detectable HIT antibodies, and in 256 healthy blood donors. For this purpose, a novel nested sequence-specific primer-polymerase chain reaction (SSP-PCR) was developed. FcgammaRIIa-R/R131 was found to be overrepresented in the HIT patients (27%) compared with the control groups (non-HIT patients [21%] and blood donors [20%]). In a subgroup of 122 well-characterized HIT patients, the genotype distribution in patients presenting with thrombocytopenia only was compared with that of patients who developed thromboembolic complications. The frequency of FcgammaRIIa-R/R131 among patients with thrombotic events was significantly elevated (37% v 17%; P = .036). Our results indicate that genotype distribution can be correlated to the clinical outcome of patients with HIT. We speculate that the reduced clearance of immune complexes in patients with the FcgammaRIIa-R/R131 allotype causes prolonged activation of endothelial cells and platelets, thus increasing the risk for thrombotic complications.
Department of Immunology and Transfusion Medicine, Ernst-Moritz-Arndt-University, Greifswald, Germany.
L E
LE
Carlsson
S
S
Santoso
G
G
Baurichter
H
H
Kroll
S
S
Papenberg
P
P
Eichler
N A
NA
Westerdaal
V
V
Kiefel
J G
JG
van de Winkel
A
A
Greinacher
D015703:Antigens, CD / Q000235:genetics*; D005838:Genotype; D006493:Heparin / Q000009:adverse effects*; D006801:Humans; D015539:Platelet Activation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D017452:Receptors, IgG / Q000235:genetics*; D012307:Risk Factors; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000150:complications / Q000235:genetics*; D013927:Thrombosis / Q000209:etiology / Q000235:genetics
D015703:Antigens, CD; C080568:Fc gamma receptor IIA; D017452:Receptors, IgG; D006493:Heparin