Published online before print October 17, 2002, doi: 10.1161/01.ATV.0000042230.26207.D2
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© 2002 American Heart Association, Inc.
Thrombosis |
Increased Platelet-Collagen Interaction Associated With Double Homozygosity for Receptor Polymorphisms of Platelet GPIa and GPIIIa
From the Department of Internal 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.
Correspondence to J.H. Beer, MD, Department of Medicine, Kantonsspital Baden, 5404 Baden, Switzerland. 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-1). 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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