Comment on: Inherited Thrombophilia and Pregnancy Complications: Should We Test?Funding The study was supported by grants APVV-17–0054, VEGA 1/0168/16, and VEGA 1/0187/17.
26 December 2019 (online)
We recently read with great interest the article by Arachchillage and Makris entitled “Inherited Thrombophilia and Pregnancy Complications: Should We Test?” and a subsequent commentary by Ruiz-Argüelles, as well as the original authors' reply. Although this response was acceptable in view of the presented viewpoints, it appears to have neglected several recently presented findings.
First, Škereňová et al have recently shown in women with recurrent fetal loss that the sticky platelet syndrome (SPS) is strongly associated with four nonsynonymous variants (rs1613662, rs1654416, rs2304167, and rs1671152) in the GP6 gene. These four polymorphisms in the coding region of GP6 are in linkage disequilibrium and create minor haplotypes at the protein level, with protein residues of PEAN. Second, it is known that homozygous PEALN allele is associated with decreased tyrosine phosphorylation of the Syk protein. This tyrosine kinase is important in adenosine diphosphate-induced and epinephrine-induced platelet activation. We currently hypothesize that this abnormal phosphorylation could lead to platelet hyperaggregability in SPS patients.
Additionally, Yagmur et al have shown for the first time in a major new retrospective study that SPS is a frequent disorder in patients with infertility and unexplained pregnancy loss history. This study found a high prevalence of SPS type II (33.2%) in 208 affected females. Moreover, the SPS patients on low-dose acetylsalicylic acid (ASA) therapy showed improved pregnancy outcome compared with SPS patients without low-dose ASA.
Thus, despite several unresolved questions, a genetic basis for at least some presentations of SPS is emerging, and we continue to propose that SPS reflects a disorder that is relevant for clinical practice, especially in patients with recurrent abortion.
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- 4 Škereňová M, Sokol J, Biringer K. , et al. GP6 haplotype of missense variants is associated with sticky platelet syndrome manifested by fetal loss. Clin Appl Thromb Hemost 2018; 24 (01) 63-69
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