{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T12:59:47Z","timestamp":1790600387158,"version":"4.1.0"},"reference-count":106,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>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\u2013Ashwell-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\u2013assisted decision-making, and interdisciplinary integration remain pressing frontiers.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1907704","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T12:20:31Z","timestamp":1790598031000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Thrombocytopenia: from physiological homeostasis imbalance to mechanism-driven precision diagnosis and therapy"],"prefix":"10.3389","volume":"17","author":[{"given":"Yuting","family":"Pan","sequence":"first","affiliation":[{"name":"Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)","place":["Hangzhou, China"]},{"name":"The First School of Clinical Medicine, Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Yao","sequence":"additional","affiliation":[{"name":"Xiangshan Hospital of TCM Medical and Health Group","place":["Ningbo, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaoya","family":"Le","sequence":"additional","affiliation":[{"name":"Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)","place":["Hangzhou, China"]},{"name":"The First School of Clinical Medicine, Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengwei","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)","place":["Hangzhou, China"]},{"name":"The First School of Clinical Medicine, Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)","place":["Hangzhou, China"]},{"name":"The First School of Clinical Medicine, Zhejiang Chinese Medical University","place":["Hangzhou, China"]},{"name":"Laboratory of Integrated Traditional Chinese and Western Medicine for Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)","place":["Hangzhou, China"]},{"name":"The First School of Clinical Medicine, Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyan","family":"Chen","sequence":"additional","affiliation":[{"name":"Laboratory of Integrated Traditional Chinese and Western Medicine for Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)","place":["Hangzhou, Zhejiang, 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