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Most CTP cases have a thrombocytopenic background and are often misdiagnosed as immune thrombocytopenia with erratically effective treatment choices. CTP also occurs during hydroxyurea treatment in patients with myeloproliferative diseases. While the aetiology of CTP remains uncertain, here we evaluate historical, theoretical and clinical findings to provide a framework for understanding CTP pathophysiology. CTP retains the intrinsic oscillatory factors defined by the homeostatic regulation of platelet count, presenting as reciprocal platelet\/thrombopoietin oscillations and stable oscillation periodicity. Moreover, CTP patients possess pathogenic factors destabilizing the platelet homeostatic system thereby creating opportunities for external perturbations to initiate and sustain the exaggerated platelet oscillations. Beyond humoral and cell\u2010mediated autoimmunity, we propose recently uncovered germline and somatic genetic variants, such as those of <jats:italic>MPL<\/jats:italic>, <jats:italic>STAT3<\/jats:italic> or <jats:italic>DNMT3A,<\/jats:italic> as pathogenic factors in thrombocytopenia\u2010related CTP. Likewise, the <jats:italic>JAK2<\/jats:italic> V617F or <jats:italic>BCR::ABL1<\/jats:italic> translocation that drives underlying myeloproliferative diseases may also play a pathogenic role in hydroxyurea\u2010induced CTP, where hydroxyurea treatment can serve as both a trigger and a pathogenic factor of platelet oscillation. Elucidating the pathogenic landscape of CTP provides an opportunity for targeted therapeutic approaches in the future.<\/jats:p>","DOI":"10.1111\/bjh.19239","type":"journal-article","created":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T15:45:07Z","timestamp":1702395907000},"page":"56-67","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The highs and lows of cyclic thrombocytopenia"],"prefix":"10.1111","volume":"204","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2317-3380","authenticated-orcid":false,"given":"Haiyu","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pathology Stanford University School of Medicine  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Villar\u2010Prados","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology and Oncology Stanford University School of 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