Decreased nitrite reductase activity of deoxyhemoglobin correlates with platelet activation in hemoglobin E/ß-thalassemia subjects

PLoS One. 2018 Sep 20;13(9):e0203955. doi: 10.1371/journal.pone.0203955. eCollection 2018.


Nitric oxide (NO) can be generated from nitrite by reductase activity of deoxygenated hemoglobin (deoxyHb) apparently to facilitate tissue perfusion under hypoxic condition. Although hemoglobin E (HbE) solutions have been shown to exhibit decreased rate of nitrite reduction to NO, this observation has never been reported in erythrocytes from subjects with hemoglobin E/ß-thalassemia (HbE/ß-thal). In this study, we investigated the nitrite reductase activity of deoxyHb dialysates from 58 non-splenectomized and 23 splenectomized HbE/ß-thal subjects compared to 47 age- and sex-matched normal subjects, and examined its correlation with platelet activity. Iron-nitrosyl-hemoglobin (HbNO) was measured by tri-iodide reductive chemiluminescence as a marker of NO generation. HbNO produced from the reaction of nitrite with deoxyHb dialysate from both non-splenectomized and splenectomized HbE/ß-thal subjects was lower than that of normal (AA) hemoglobin subjects. P-selectin expression, a marker of platelet activation, at baseline and in reactivity to stimulation by adenosine diphosphate (ADP), were higher in HbE/ß-thal subjects than normal subjects. HbNO formation from the reactions of nitrite and deoxyHb inversely correlated with baseline platelet P-selectin expression, HbE levels, and tricuspid regurgitant velocity (TRV). Nitrite plus deoxygenated erythrocytes from HbE/ß-thal subjects had a lower ability to inhibit ADP-induced P-selectin expression on platelets than erythrocytes from normal subjects. We conclude that deoxyHb in erythrocytes from HbE/ß-thal subjects has a decreased ability to reduce nitrite to NO, which is correlated with increased platelet activity in these individuals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Platelets / metabolism
  • Female
  • Hemoglobin E / metabolism*
  • Hemoglobins / metabolism*
  • Humans
  • Male
  • Nitrite Reductases / metabolism*
  • P-Selectin / metabolism
  • Platelet Activation / physiology*
  • beta-Thalassemia / metabolism*


  • Hemoglobins
  • P-Selectin
  • deoxyhemoglobin
  • Hemoglobin E
  • Nitrite Reductases

Grant support

This study was supported by grants from Mahidol University, the Office of the Higher Education Commission and Mahidol University under the National Research Universities Initiative, Mahidol University, and the Thailand Research Fund through the Royal Golden Jubilee Ph.D. Program (Grant No. PHD/0002/2555) to AC and NS. KoP is supported by the Thailand Research Fund - Distinguished Research Professor Grant DPG5980001. Additional support is from an Albert Einstein College of Medicine Global Health Microgrant (REH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.