Platelet glycoprotein Ibalpha polymorphisms and function evaluated by the platelet function analyzer PFA-100 in patients with lupus anticoagulant: the association with thromboembolic disease.
Lupus anticoagulants (LA) are a surrogate marker for the risk of thromboembolic disease (TE). However, not all individuals with LA acquire TE, and it is desirable to distinguish those at risk for TE from those without. Platelets polymorphisms may contribute to the risk of TE, mainly those of glycoprotein (GP)Ibalpha: these are the variable number of tandem repeats (VNTR) and a dimorphism in the Kozak region, which affect platelet plug formation in healthy individuals under high shear stress rates. We determined polymorphisms within the GPIbalpha in individuals with persistent LA and a history of TE (LA/TE+) and in those without TE (LA/TE-). Further, we measured platelet function, as estimated by the collagen-epinephrine closure time (CEPI-CT) of the platelet function analyzer PFA-100 and compared all data with healthy controls. There was no difference of the VNTR alleles compared to healthy controls. The (-5)C allele of the Kozak dimorphism was significantly more frequent in LA patients compared to controls (p = 0.04), as a result of its increased frequency in LA/TE+ (vs controls p = 0.04), but there was no difference between LA/TE+ and LA/TE-. The increased frequency of the (-5)C allele resulted in an overrepresentation of (-5)TC genotype in the LA/TE+ group (p = 0.02) but not in a subgroup of 18 patients with arterial disease. The CEPI-CT of the PFA-100 was shorter in LA/TE+ than in LA/TE- (p = 0.044), but this difference did not persist after exclusion of patients with low platelet counts or low ristocetin cofactor activity. Unlike in healthy individuals, the CEPI-CT was not related to any Kozak dimorphism, neither in LA/TE-, nor in LA/TE+. Thus, the Kozak dimorphism may just contribute to stronger factors disposing individuals with LA towards TE without any discernible effect on their in vitro platelet function estimated by the PFA-100.
Jilma-Stohlawetz
Petra
P
Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria. petra.jilma@meduniwien.ac.at
Jilma
Bernd
B
Mannhalter
Christine
C
Bencur
Peter
P
Pabinger
Ingrid
I
Vormittag
Rainer
R
Dunkler
Daniela
D
Panzer
Simon
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D003094:Collagen / Q000737:chemistry; D004837:Epinephrine / Q000737:chemistry; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006801:Humans; D016682:Lupus Coagulation Inhibitor / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010979:Platelet Function Tests / Q000295:instrumentation / Q000379:methods; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D012307:Risk Factors; D033081:Shear Strength; D013314:Stress, Mechanical; D020080:Tandem Repeat Sequences / Q000235:genetics*; D013923:Thromboembolism / Q000235:genetics* / Q000378:metabolism
D016682:Lupus Coagulation Inhibitor; D019038:Platelet Glycoprotein GPIb-IX Complex; D003094:Collagen; D004837:Epinephrine