Vector of Changes in the hemostasis System in Rett Syndrome in Children

Background. Rett syndrome (RS) is a monogenic X-linked hereditary disease caused by pathogenic variants of the MECP2 gene, characterized by regression of psychomotor development, a progressive course, and multisystem manifestations. This condition is associated with high mortality. Despite the considerable amount of accumulated data on the spectrum of MECP2 genetic variants, the pathogenetic mechanisms of disease progression that determine the clinical and laboratory manifestations of RS remain insufficiently studied. Manifestations of hemorrhagic syndrome (epistaxis, ecchymoses) have been described in girls with RS. It is suggested that a prolonged inflammatory process may occur in this category of patients, contributing to coagulation disorders. In addition, there is evidence of the influence of pathogenic MECP2 gene variants on the coagulation system. An additional risk factor is antiepileptic drugs, which can affect both the platelet (reduction of platelet aggregation when interacting with GPIIb/IIIa receptors) and plasma components of hemostasis (decreased fibrinogen levels), potentially increasing the tendency toward hemorrhagic manifestations. Thus, the combination of these factors creates prerequisites for an imbalance in the hemostasis system in patients with RS. In this regard, the study of hemostasis features in this orphan pathology appears relevant.

The aim of the study — to assess the direction of changes in the hemostasis system in girls with RS.

Methods. The main group included 52 girls with a verified diagnosis of RS, followed up at the Pediatrics and Child Health Research Institute in Petrovsky National Research Centre of Surgery from January 2022 to December 2025. The control group consisted of 69 conditionally healthy girls. All children underwent a comprehensive examination, including physical examination, complete blood count, and coagulogram.

Results. The groups were comparable in sex and age. In girls with RS, a statistically significant decrease in the median activated partial thromboplastin time was revealed: 31.15 s (28.9; 33.5) compared with the control group (p = 0.000). At the same time, a statistically significant increase in the plasminogen level was noted: 106% (96; 112), p = 0.004. According to the complete blood count, statistically significant differences from the control group girls were recorded in patients with RS for the following parameters: white blood cell count — 7.84 × 10⁹/L (6.35; 9.02), p < 0.000; lymphocyte count — 3.15 × 10⁹/L (2.62; 3.98), p = 0.003; platelet-to-lymphocyte ratio (PLR) — 90.81 (76.97; 111.58), p = 0.016.

Conclusion. The obtained results indicate an association of RS with changes in the plasma component of hemostasis and activation of the fibrinolytic system. A possible pathogenetic relationship between impaired MECP2 protein function and the development of systemic manifestations, including hemostasis disorders, in patients with RS is suggested.

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