Inherited or Immunological Thrombocytopenia: The Complex Nature of Platelet Disorders in 22q11.2 Deletion Syndrome

Abstract

22q11.2 deletion syndrome (22q11.2DS) is one of the most common congenital malformation syndromes resulting from disrupted embryonic development of pharyngeal pouches. The classical triad of symptoms described by Angelo DiGeorge is frequently accompanied by hematological and immune disorders. While it is well-established that patients with 22q11.2DS have an increased risk of recurrent autoimmune cytopenias, including immune thrombocytopenia, the platelet abnormalities in this population are more complex and multifaceted. Given this issue, we conducted a comprehensive literature review on platelet disorders in 22q11.2DS using accessible databases (PubMed and Scopus). We aimed to outline previous studies limitations and most urgent challenges concerning thrombocytopenia in these patients. One characteristic finding frequently observed in 22q11.2DS is mild macrothrombocytopenia caused presumably by the loss of one GP1BB allele, encoding the element of the GPIb–IX–V complex. This structure plays a central role in thrombocyte adhesion, aggregation, and subsequent activation. Recent studies suggest that defective megakaryopoiesis and impaired vasculogenesis may strongly influence platelet and hemostasis disorders in 22q11.2DS. Furthermore, the phenotypic manifestation may be modulated by epigenetic factors and gene expression modifiers located outside the deletion region. Although the final hemorrhagic phenotype is typically mild, these patients may require more frequent transfusions following major surgical procedures. Despite the risk of thrombocytopenia and thrombocytopathy, there is a lack of large-scale research on hematological anomalies in 22q11.2DS, and the available results are often inconclusive. Given the complexity of hemostatic disorders, it is essential to establish specific recommendations for perioperative management and autoimmune cytopenias treatment within this population.

Keywords

22q11.2 deletion syndrome - DiGeorge syndrome - inherited thrombocytopenia - immune thrombocytopenia - Bernard–Soulier syndrome

Ethical Approval

The work described in this article has been performed in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki) for experiments involving humans; EU Directive 2010/63/EU for animal experiments and uniform requirements for manuscripts submitted to biomedical journals. This study was approved by the Local Ethical Committee at the Medical University of Lodz (decision No. RNN/261/23/KE).

Authors' Contributions

B.U. was responsible for writing the original draft, literature review, and conceptualization. Z.U. was responsible for visualization. K.B-P. was responsible for reviewing and editing the manuscript. E.S. was responsible for literature review. W.M. was responsible for supervision. S.J. was responsible for reviewing and editing the manuscript, conceptualization, and supervision. All authors have read and agreed to the published version of the manuscript.

Publication History

Article published online:
13 January 2025

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