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The effects of platelet receptor GPIIb/IIIa polymorphism (Leu Pro33) on the receptor expression and platelet aggregation in patients with ischaemic stroke
Platelet hyperaggregation in ischaemic stroke patients is a proven finding, and associated with increased expression of the platelet surface GPIIb/IIIa receptor. The polymorphism occurs at nucleotide position 1565 of the GPIIIa gene resulting a 33Leu-Pro change. Data are conflicting regarding the abnormal function of the PlA1/A2 receptor in stroke. The aim of the study was to address the difference of platelet receptor function in ischemic stroke patients with the wild PlA1/A1 and heterozygous PlA1/A2 genotype. A total of 51 patients with PA1/A1 and 54 patients with PlA1/A2 genotypes were enrolled. Polymerase chainreaction was used for genotyping of platelets. Platelet aggregation was measured in whole blood and in platelet rich plasma (PRP). Flow cytometry was used for measuring surface molecule expression (CD42b, CD41a, CD61, CD62P) and fibrinogen binding capacity of cells with phosphate buffer solution (PBS) in comparison with activation by ristocetin in whole blood as well as by adenosine diphosphate (ADP) in PRP. In comparison with wild types, platelets carrying the PlA1/A2 genotypes showed hyperaggregation measuredin whole blood and induced by ristocetin (p< 0.05). Using whole blood flow cytometry with ristocetin induction, the CD62P+/FIB- (P selectin) and the CD62P+/FIB+ were more expressed in heterozygous platelets as compared to wild types (p< 0.01 and p< 0.05), respectively. According to mean fluorescence intensity with ADP induction, an increased expression of CD61+, CD61+/CD41+ and CD62P+ in PlA1/A2 platelets were detectedas compared to the group carrying the wild type (p< 0.0001, p= 0.006, p= 0.0001), respectively. These findings support the possibility that in ischaemic stroke patients, platelets carrying PlA1/A2 genotypes can be activated by different inductors in a way, which leads to permanent hyperfunction of platelet surface receptor GPIIIa.

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Authors: Endre Pongrácz, Katalin Schweitzer, József Furész, János Fent, Attila Tordai, Zoltán Nagy

Keywords:

  • Year: 2007
  • Number: 4
  • Referance No: 14633
  • Figure 1. Results of platelet aggregation study measured in whole blood. Measuring after ADP, collagen and ristocetin induction according to different genotypes (NS= non significant).
  • Figure 2. Flow cytometry evaluation of PlA1/A1 and PlA1/A2 platelets in whole blood following PBS incubation or ristocetin induction. 2/A: CD62P+, 2/B: CD62P+/fibrinogen+ values given in percents of all cells.
  • Figure 3. Flow cytometry evaluation of PlA1/A1 and PlA1/A2 platelets in platelet rich plasma following PBS incubation or ADP induction. 3/A: CD42b positivity, 3/B: CD61+/CD41+, 3/C: CD61+, 3/D: CD62P+ values given in fluorescence intensity.

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