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The aim of our study was to evaluate GP6 gene in patients with sticky platelet syndrome (SPS) and fetal loss. Platelet aggregability was tested with platelet-rich plasma using PACKS-4 aggregometer (Helena Laboratories). High-resolution melting analysis on LightCycler 480 II (Roche Diagnostics) was used for single-nucleotide polymorphism (SNP) genotyping. We examined 64 patients with SPS and 54 control participants. We found significantly higher occurrence of 5 SNPs in patients with SPS versus controls (rs1671152, rs1654433, rs1613662, rs1654416, and rs2304167). Moreover, the haplotype analysis showed a significantly higher occurrence of 7 haplotypes in patients with SPS compared to controls (acgg and aagg in GP6_5reg haplotype; ccgt in GP6_3reg haplotype; gg and ta in GP6_REG haplotype; SKTH and PEAN in GP6_PEAN haplotype). Our results, especially higher occurrence of 4 nonsynonymous variants within the coding region, support the idea that GP6 polymorphisms are associated with the platelet hyperaggregability accompanied by fetal loss.

Disequilibrium of hemostasis is central to the pathogenesis of all thromboses, and platelets are essential for primary hemostasis. The platelet membrane glycoprotein receptor is involved in the clot formation in blood; therefore, the changes in related genes could impair platelet aggregation in patients with sticky platelet syndrome (SPS). Patients with SPS who experienced fetal loss were shown to harbor a risk haplotype at GP6 locus. The aim of the study was to examine the genetic linkage of this selected risk haplotype with single nucleotide variations (SNVs) in the coding sequence of the GP6 gene in order to identify possible functional SNVs in association with SPS and fetal loss. A total of 37 patients with SPS manifested fetal loss, and 42 healthy controls were enrolled in the study. The SPS was diagnosed with platelet aggregometry. The SNVs were determined by dideoxy sequencing and high-resolution melting analysis. The missense variations were detected in patients with risk haplotype only. The association analysis showed association of the minor alleles with the SPS manifested by fetal loss as follows-rs1671152 (odds ratio [OR]: 4.667, 95% confidence interval [CI]: 1.462-14.89, P = .006), rs2304167 (OR: 5.085, 95% CI: 1.605-16.10, P = .003), and rs1654416 (OR: 5.085, 95% CI: 1.605-16.10, P = .003). Using the Expectation-Maximization (EM) algorithm, the estimated minor haplotype with predicted protein residue PEAN was significantly associated with the given phenotype (OR: 4.746, 95% CI: 1.486-15.15, P = .005). We have shown that haplotype PEAN associated with SPS and manifested by fetal loss and suggest that the mechanism involved in the action of GPVI has significant effect on GPVI-mediated signal transduction through Syk-phosphorylation.

The knowledge on the etiology of thrombosis has increased tremendously over the past decades. Nevertheless, Virchow triad is still traditionally invoked to explain mechanisms leading to thrombosis, alleging concerted roles for abnormalities in blood composition, vessel wall components, and blood flow in the development of arterial and venous thrombosis. Recent decades have been focused primarily on describing abnormalities in blood composition, including defects of coagulation proteins and platelets. Although defects of coagulation factors are relatively well-described in the literature, prothrombotic platelet disorders are still less understood. One such defect, the Wien-Penzing defect was first described in 1991. Another platelet defect is sticky platelet syndrome (SPS). In this article, we review information about SPS, and we propose a new definition and standardization of diagnostic criteria. We also attempt to explain the causes and consequences of this condition., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Introduction: Thrombophilia increases the risk of venous thrombosis during pregnancy and may predispose to gestational vascular complications., Objective: The aim of this study is to evaluate the variability of GP6 regulatory regions in a group of patients with platelet hyperaggregability manifested as miscarriage compared with control subjects., Methods: We examined 27 female patients with platelet hyperaggregability and history of spontaneous abortion and 42 healthy women. Platelet hyperaggregability was established by light transmission aggregometry. We also assessed eight SNPs within the GP6 gene., Results: We found a higher occurrence of three SNPs in patients with platelet hyperaggregability and history of miscarriage (rs1671152, rs1654433, rs1671215). The haplotype analysis showed a significant higher occurrence of two haplotypes (ACGG, CCGT)., Conclusions: Our results support the idea that genetic variability of GP6 regulatory regions can be associated with platelet hyperaggregability - a possible cause of miscarriage.

Introduction: The aim of this study was to evaluate the genetic variability of selected single nucleotide polymorphisms (SNPs) within GAS6 and PEAR1 genes and explore the association between selected SNPs and risk for fetal loss in women with sticky platelet syndrome (SPS)., Materials and Methods: We examined 23 female patients with SPS and history of spontaneous abortion, and 42 healthy women who served as controls. The diagnosis of SPS was established by light transmission aggregometry according to methods and criteria developed by Mammen et al. We also assessed four SNPs within the GAS6 gene (rs7400002, rs1803628, rs8191974, rs9550270) and two SNPs within PEAR1 gene (rs12041331, rs12566888)., Results: We identified two SNPs within PEAR1 gene (rs12041331, rs12566888) and one SNP within GAS6 gene (rs9550270) that have higher occurrence in SPS patients with history of abortion. An increased risk for abortion was observed in carriers of the rs7400002 within GAS6 gene. Conversely, we found that the T allele of PEAR1 c. -9-4663G > T polymorphism appears to be protective for fetal loss., Conclusion: Our results support the idea that genetic variability of GAS6 and PEAR1 genes may be associated with platelet hyperaggregability. The study also suggests a possible polygenic type of SPS heredity., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Introduction: Sticky platelet syndrome (SPS) is most likely a hereditary thrombophilia characterized by platelet hyperaggregation after low concentrations of platelet inducers--adenosine diphosphate and/or epinephrine. We present 9 kindreds with SPS familial occurrence., Material and Methods: Familial trait of SPS was looked up in the database of the National Center of Hemostasis and Thrombosis. Families with at least 3 SPS-positive members were studied, described, and presented., Results: In the group of 1093 symptomatic patients, SPS was confirmed in 240 cases. Familial occurrence with at least 3 SPS-positive relatives was found in 9 cases., Conclusion: The exact pathogenesis of SPS is not sufficiently explained. Our findings seem to support the idea that SPS might have an autosomal dominant hereditary fashion.

Objective: To evaluate the GP6 gene polymorphism in patients with sticky platelet syndrome (SPS) and fetal loss., Design: Genetic association study., Setting: Perinatal center., Patient(s): Twenty-seven patients with SPS, manifested as fetal loss, and 42 control subjects without SPS and no history of fetal loss and thrombosis., Intervention(s): SPS was diagnosed by platelet aggregometry (PACKS-4 aggregometer; Helena Laboratories). Seven single-nucleotide polymorphisms (SNPs) of the GP6 gene were evaluated., Main Outcome Measure(s): Occurrence of SNPs of the GP6 gene in SPS patients versus control subjects., Result(s): We found a higher occurrence of three SNPs of the GP6 gene in SPS patients versus control subjects (rs1671153: 0.204 vs. 0.048, odds ratio [OR] 5.116, 95% confidence interval [CI] 1.536-17.03; rs1654419: 0.204 vs. 0.071, OR 3.326, 95% CI 1.149-9.619; rs1613662: 0.204 vs. 0.071, OR 3.326, 95% CI 1.149-9.619). The haplotype analysis showed a significantly higher occurrence of two haplotypes (CTGAG in haplotype 5: 0.185 vs. 0.059, OR 3.568, 95% CI 1.142-11.14; and CGATAG in haplotype 6: 0.204 vs. 0.048, OR 4.961, 95% CI 1.488-16.53)., Conclusion(s): Our results, especially the higher occurrence of haplotypes CTGAG and CGATAG in SPS patients, support the idea that GP6 gene polymorphism may be associated with platelet hyperaggregability, a possible cause of fetal loss., (Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Sticky platelet syndrome (SPS) is a disorder with familial occurrence and autosomal dominant trait characterized by platelet hyperaggregability in response to a low concentration of adenosine diphosphate (ADP) and/or epinephrine (EPI). The etiology of SPS may be associated with platelet microRNAs (miRNAs), which are considered as potential biomarkers of platelet function and antiplatelet therapy. We were monitoring the expression of platelet miRNAs in patients with laboratory diagnosed SPS and healthy controls. We have found a statistically significant increased expression of both miR-423-5p and miR-338-3p as well as a statistically significant decreased expression of miR-425-5p between the group of patients with diagnosed SPS type II and the group of healthy controls, which seems to be an interesting issue for a further research. [ABSTRACT FROM AUTHOR]