Cyclic thrombocytopenia associated with estradiol: a case report

Autor: Ningbo Pang, Yingwei Li, Kangxi Zhou, Chunliang Liu, Rong Yan, Chenglin Sun, Weiling Xiao, Changgeng Ruan, Zhimin Zhai, Kesheng Dai
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Hematology, Vol 28, Iss 1 (2023)
Druh dokumentu: article
ISSN: 16078454
1607-8454
DOI: 10.1080/16078454.2023.2240140
Popis: ABSTRACTObjectives Cyclic thrombocytopenia (CTP) is a rare blood disorder characterized by periodic fluctuations in platelet counts. CTP usually appears in pre-menopausal women, and these fluctuations of platelets are in phase with the menstrual cycle. CTP is a heterogeneous disease, and the pathogenic mechanism is still unclear. Therefore, it harbors great significance for exploring the association of fluctuations in platelet counts with hormonal-cycle.Materials Firstly, we washed human platelets from healthy volunteers following the Declaration of Helsinki. Flow cytometer was employed to measure the mitochondrial inner transmembrane potential (ΔΨm) depolarization, PS exposure, P-selectin expression, and GPIIb/IIIa activation in platelets. In addition, western blot detected the related protein expression. The corresponding assay kit measured the caspase-3 and PDE3A activity. Finally, flow cytometry determined mouse platelets labeled with calcein.Results We find a reverse relationship between the platelet count and serum estradiol (E2) level in a CTP patient. We demonstrated that E2 induces platelet apoptosis in vitro and platelet clearance in vivo. We further discovered that E2 activates phosphodiesterase 3A, which inhibits protein kinase A (PKA), leading to PKA-mediated platelet apoptosis. Activation of PKA protected platelets from E2-induced thrombocytopenia and elevated the number of mice circulatory platelets.Conclusions We find that E2 induces platelet apoptosis and clearance through PDE3A-mediated PKA inhibition. Activation of PKA rescues E2-induced thrombocytopenia in mice. Thus, our study reveals a pathogenesis of E2-related CTP and suggests promising therapeutic strategies for the disease.
Databáze: Directory of Open Access Journals
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