on October 17, 2002
Published online before print October 17, 2002, doi: 10.1161/01.ATV.0000042230.26207.D2
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Submitted on August 9, 2002
Accepted on September 24, 2002
Increased Platelet-Collagen Interaction Associated With Double Homozygosity for Receptor Polymorphisms of Platelet GPIa and GPIIIa
Luca Pontiggia ;
From the Department of Medicine (R.L.), Helsinki University Central Hospital, Wihuri Research Institute Helsinki, Finland; and the Department of Medicine (J.H.B., L.P., S.P., H.R.S., M.B.), Laboratory for Thrombosis Research, Kantonsspital Baden, Switzerland.
* To whom correspondence should be addressed. E-mail: hansjuerg.beer{at}ksb.ch.
Objective—There is considerable controversy regarding the clinical role of the single-nucleotide polymorphisms (SNPs) of the platelet glycoprotein receptor GPIa C807T and the PlA1/A2 of GPIIIa as cardiovascular risk factors. We hypothesized that two combined SNPs in their homozygous prothrombotic forms could clarify their pathophysiological impact.
Methods and Results—We identified a family with a striking history of premature cardiovascular events and a high frequency of the prothrombotic form of the two SNPs. From this family, the platelets of a healthy, 27-year-old propositus with this double homozygosity were compared with three matched male neutral gene variant controls. The propositus had shortened PFA-100 closure times and an increased platelet aggregation response to collagen. Platelet deposition to collagen was augmented under the blood flow conditions of a high shear rate model (1600 s-). Platelet adhesion on collagen monomers was induced in a static system, leading to the promotion of subsequent procoagulant activity.
Conclusions—The combined homozygous prothrombotic SNPs of GPIa and GPIIIa are associated with an increased platelet-collagen interaction and procoagulant activity that can be readily demonstrated in several independent systems. Our patient may serve as a useful model for the functional consequences of two combined, potentially procoagulant, platelet SNPs.
Key words: platelet • receptor • myocardial infarction • collagen • polymorphism
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