title: Increased prostacyclin levels inhibit the aggregation and activation of platelets via the PI3K-AKT pathway in prolonged isolated thrombocytopenia after allogeneic hematopoietic stem cell transplantation.
abstract: OBJECTIVE
  The aim of this study was to investigate the role of prostacyclin (PGI2) in prolonged isolated thrombocytopenia (PT) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) and the effect of PGI2 on the activation and aggregation of platelets in PT.
  
  
  METHODS
  We enrolled 37 patients with PT and 36 controls following allo-HSCT in this study. Platelet aggregation and activation and PGI2 levels were measured. Endothelial progenitor cells (EPCs) from either PT or control patients were cultured ex vivo with serum from either PT or control patients. PGI2 secretions were then measured. PGI2 was added to the platelets ex vivo, and platelet aggregation and activation and PI3K/Akt phosphorylation were analyzed.
  
  
  RESULTS
  A higher PGI2 level was observed in the PT patients. The activation and aggregation of platelets were significantly lower in the PT patients. EPCs from PT patients cultured in PT serum secreted higher levels of PGI2, and PGI2 inhibited platelet activation and aggregation in a concentration-dependent manner ex vivo. PI3K/Akt phosphorylation of platelets was regulated by PGI2 after allo-HSCT. Disease status, serum PGI2 level and platelet aggregation were independent risk factors in patients with PT after allo-HSCT.
  
  
  CONCLUSIONS
  Higher PGI2 levels and lower platelet activation and aggregation occurred simultaneously in PT patients. PGI2 inhibited platelet activation and aggregation, probably by regulating the phosphorylation of PI3K/Akt.
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, People's Republic of China; Collaborative Innovation Center of Hematology, Peking University, People's Republic of China. Electronic address: zhangxh100@sina.com.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Zhang
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, People's Republic of China; Collaborative Innovation Center of Hematology, Peking University, People's Republic of China.
authors.forename: Shi-Yuan
authors.initials: SY
authors.lastname: Zhou
authors.affiliation: Department of Hematology, Beijing Hospital, Ministry of Health, Beijing, People's Republic of China.
authors.forename: Ru
authors.initials: R
authors.lastname: Feng
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, People's Republic of China.
authors.forename: Ya-Zhe
authors.initials: YZ
authors.lastname: Wang
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Kong
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, People's Republic of China.
authors.forename: Jia-Min
authors.initials: JM
authors.lastname: Zhang
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Peking University People's Hospital, Department of Clinical Laboratory, Beijing, People's Republic of China.
authors.forename: Jing-Zhong
authors.initials: JZ
authors.lastname: Zhao
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, People's Republic of China.
authors.forename: Qian-Ming
authors.initials: QM
authors.lastname: Wang
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, People's Republic of China.
authors.forename: Fei-Er
authors.initials: FE
authors.lastname: Feng
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, People's Republic of China.
authors.forename: Xiao-Lu
authors.initials: XL
authors.lastname: Zhu
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, People's Republic of China.
authors.forename: Feng-Rong
authors.initials: FR
authors.lastname: Wang
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, People's Republic of China.
authors.forename: Jing-Zhi
authors.initials: JZ
authors.lastname: Wang
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, People's Republic of China.
authors.forename: Huan
authors.initials: H
authors.lastname: Chen
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, People's Republic of China.
authors.forename: Lan-Ping
authors.initials: LP
authors.lastname: Xu
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, People's Republic of China.
authors.forename: Yan-Rong
authors.initials: YR
authors.lastname: Liu
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, People's Republic of China.
authors.forename: Kai-Yan
authors.initials: KY
authors.lastname: Liu
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, People's Republic of China; Collaborative Innovation Center of Hematology, Peking University, People's Republic of China.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Huang
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000378:metabolism / Q000473:pathology; D011464:Epoprostenol / Q000097:blood* / Q000378:metabolism; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D015539:Platelet Activation; D010974:Platelet Aggregation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013921:Thrombocytopenia / Q000097:blood* / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D011464:Epoprostenol; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Hematopoietic stem cell transplantation; Platelet activation; Platelet aggregation; Prolonged isolated thrombocytopenia; Prostacyclin