ReviewFrontiers in immunology2026
Thrombocytopenia: from physiological homeostasis imbalance to mechanism-driven precision diagnosis and therapy.
Review in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Thrombocytopenia is not a monolithic disease but a common final pathway of disrupted platelet homeostasis spanning production, clearance, and distribution. The traditional count-centric paradigm, relying on empirical transfusion or steroid administration, frequently obscures underlying mechanistic drivers. This review advances a framework progressing from physiological homeostasis imbalance through pathological mechanisms to precision diagnosis and therapy. Recognizing that immune-targeted therapies are only appropriate when cytopenia is genuinely immune-mediated, we systematically deconstruct both immune and non-immune mechanisms to enable accurate etiological anchoring and avoid inappropriate immunomodulation. We systematically deconstruct the multidimensional pathogenesis along five axes: impaired production, immune-mediated destruction, distributional abnormality, consumptive loss, and pseudothrombocytopenia. Key molecular insights include megakaryocyte transcriptional governance (GATA-1, FLI-1, RUNX1), the platelet desialylation-Ashwell-Morell receptor clearance axis, complement cascade activation, and FcRn-mediated IgG homeostasis. Building on this mechanistic foundation, we propose a three-stage diagnostic algorithm: artifact exclusion, mechanistic localization via non-invasive biomarkers (IPF, TPO, autoantibodies), and etiological anchoring. In the therapeutic landscape, Thrombopoietin receptor agonists (TPO-RAs), FcRn antagonists (efgartigimod and rozanolixizumab), BTK inhibitors (rilzabrutinib), and Syk inhibitors have reshaped ITP management, while complement pathway inhibition (eculizumab, ravulizumab, narsoplimab) has transformed thrombotic microangiopathy outcomes.We posit that thrombocytopenia management has entered the precision medicine era; nevertheless, dynamic biomarker development for refractory cases, artificial intelligence-assisted decision-making, and interdisciplinary integration remain pressing frontiers.
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