Red blood cells microparticles are associated with hemolysis markers and may contribute to clinical events among sickle cell disease patients

  • Oladele Simeon OlatunyaEmail author
  • Carolina Lanaro
  • Ana Leda Longhini
  • Carla Fernanda Franco Penteado
  • Kleber Y. Fertrin
  • Adekunle Adekile
  • Sara T. O. Saad
  • Fernando Ferreira Costa
Original Article


Microparticles are sub-micron vesicles possessing protein and other materials derived from the plasma membrane of their parent cells, and literature suggests that they may have a role in the pathophysiology and downstream manifestations of sickle cell disease (SCD). The contributions of red blood cells microparticles (RMP) to the pathogenic mechanisms and clinical phenotypes of SCD are largely unknown. There is a controversy as to whether the proportions of intravascular hemolysis (approximately ≤ 30% of total hemolysis) would be enough to explain some complications seen in patients with SCD. We investigated RMP among 138 SCD patients and 39 HbAA individuals. Plasma RMPs were quantified by flow cytometry, plasma hemoglobin and heme by colorimetric assays, and haptoglobin and hemopexin by ELISA. The patients had higher RMP, plasma hemoglobin, and heme compared to the controls. On the contrary, haptoglobin and hemopexin were depleted in the patients. The RMP correlated positively with heme, lactate dehydrogenase, plasma hemoglobin, serum bilirubin, reticulocyte counts, and tricuspid regurgitant jet velocity of the patients. Contrarily, it correlated negatively with HbF, hemopexin, red blood cells counts, hemoglobin concentration, and haptoglobin. Although patients treated with hydroxyurea had lower RMP, this did not attain statistical significance. Patients with sickle leg ulcer and elevated tricuspid regurgitant jet velocity had higher levels of RMP. In conclusion, these data suggest that RMPs are associated with hemolysis and may have important roles in the pathophysiology and downstream complications of SCD.


Sickle cell disease Red blood cells microparticles Hemolysis Clinical manifestations 



Authors acknowledge with thanks the supports received from Prof. Oluwadiya KS of the College of Medicine, Ekiti State University, for statistical analysis. Authors also acknowledge with thanks the supports received from participants during the study.

Authors’ contributions

All authors contributed to critical aspects of the study. OSO, AA, and FFC conceived and designed the study. OSO wrote the paper, collected and analyzed the data, and performed the experiments. CL, CFP, and ALL performed the experiments. KYF, STS, and FFC managed the patients. FFC supervised the study. All authors participated in reviewing the manuscript for important intellectual contents and agreed to the final version.

Funding information

This study was supported by grant nos. 2014/00984-3 from FAPESP, and grant nos. 2015/141693-0 from CNPq, Brazil.

Compliance with ethical standards

The study was conducted according to the international standards of biomedical and human research. The study was approved by the institutional review board of UNICAMP no. CAAE 54031115.9.0000.5404, and written informed consent was obtained from all participants before being included in the study.

Competing interests

The authors declare that they have no conflict of interest.

Supplementary material

277_2019_3792_MOESM1_ESM.docx (23 kb)
ESM 1 (DOCX 22 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Oladele Simeon Olatunya
    • 1
    • 2
    Email author
  • Carolina Lanaro
    • 1
  • Ana Leda Longhini
    • 1
  • Carla Fernanda Franco Penteado
    • 1
  • Kleber Y. Fertrin
    • 1
  • Adekunle Adekile
    • 3
  • Sara T. O. Saad
    • 1
  • Fernando Ferreira Costa
    • 1
  1. 1.Hematology and Hemotherapy Center (Hemocentro)University of Campinas (UNICAMP)CampinasBrazil
  2. 2.Department of Pediatrics, College of MedicineEkiti State UniversityAdo EkitiNigeria
  3. 3.Department of Pediatrics, Faculty of MedicineKuwait UniversityJabriyaKuwait

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