Premium
Defective platelet response to arachidonic acid and thromboxane A 2 in subjects with Pl A2 polymorphism of β 3 subunit (glycoprotein IIIa)
Author(s) -
Andrioli Giuseppe,
Minuz Pietro,
Solero Pietro,
Pincelli Silver,
Ortolani Riccardo,
Lussignoli Sabrina,
Bellavite Paolo
Publication year - 2000
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2000.02300.x
Subject(s) - platelet , thromboxane a2 , arachidonic acid , glycoprotein , polymorphism (computer science) , platelet membrane glycoprotein , medicine , protein subunit , microbiology and biotechnology , endocrinology , chemistry , immunology , biology , biochemistry , allele , gene , enzyme
The membrane complex α IIb β 3 is the major receptor for fibrinogen and is involved in platelet adhesion and aggregation. Evidence has been presented that the Pl A2 allele of the β 3 Pl A1/A2 gene polymorphism might be an independent risk factor for coronary thrombosis, but the matter is still controversial. We investigated the relationship between this polymorphism and possible alterations of platelet functions in vitro . The platelet adhesion to fibrinogen‐coated microplate wells and the aggregation induced by several different agonists were tested in 63 healthy volunteers, among them, 49 subjects with Pl A1/A1 polymorphism, 12 subjects with Pl A1/A2 polymorphism and two subjects with Pl A2/A2 polymorphism. Subjects with Pl A1/A2 polymorphism or with Pl A2/A2 polymorphism showed significantly lower platelet responses as compared with Pl A1/A1 subjects when either arachidonic acid or the thromboxane A 2 analogue, U46619, were used as agonists. In resting condition and after thrombin or ADP stimulation, platelet function was normal in all the subjects. An increased sensitivity to the anti‐aggregatory effect of acetylsalicylic acid was observed in platelets from subjects with the Pl A2 allele. Finally, using a flow‐cytometric evaluation and determining the β‐thromboglobulin plasma levels, we did not find any evidence of a Pl A2 platelet hyper‐reactivity ex vivo . Our findings are not consistent with the hypothesis that the purported increase of cardiovascular risk in these subjects may be as a result of platelet hyperactivation. On the contrary, the Pl A2 allele is associated with a platelet functional deficiency, specifically linked to the activation of the fibrinogen receptor by thromboxane A 2 .