Oxidative stress in sickle cell disease; more than a DAMP squib.
van Beers EJ1, van Wijk R2.
Clin Hemorheol Microcirc. 2018;68(2-3):239-250. doi: 10.3233/CH-189010.

Abstract
Sickle cell disease (SCD) is a monogenetic disorder marked by hemolytic anemia and vaso-occlusive complications. The hallmark of SCD is the intracellular polymerization of sickle hemoglobin (HbS) after deoxygenation, and the subsequent characteristic
shape change (sickling) of red cells. Vaso-occlusion occurs after endothelial activation, expression of adhesion molecules and subsequent adhesion of leucocytes and sickle erythrocytes to the vascular wall. Here we review how oxidative stress from
various sources influences this process. Emerging evidence points towards a dominant mechanism in which innate immune receptors, such as Toll like receptor 4, activate nicotinamide adenine dinucleotide phosphate (NADPH) oxidases to produce reactive
oxygen species (ROS) which in turn enables downstream pro-inflammatory signaling and subsequent endothelial activation. By serving as an iron donor for the Fenton reaction, heme radically increases the amount of ROS further, thereby increasing the signal
originating from the innate immune receptor and downstream effects of innate immune receptor activation. In SCD this results in the production of pro-inflammatory cytokines, endothelial activation and leucocyte adhesion, and eventually vaso-occlusion.
Any intervention to stop this cascade, including Toll like receptor blockade, NADPH oxidase inhibition, ROS reduction, heme scavenging, iron chelation, or anti-adhesion molecule antibodies has been successfully used in pre-clinical studies and holds
promise for patients with SCD.

KEYWORDS:
Sickle cell disease; heme; reactive oxygen species

PMID: 29614635 DOI: 10.3233/CH-189010

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Therapeutic phlebotomy during major sickle cell disease in Togo.
Padaro E1, Kueviakoe IMD2, Agbétiafa K3, Magnang H2, Mawussi K4, Layibo Y2, Vovor A4
Author information
Medecine et Sante Tropicales, 01 Feb 2019, 29(1):106-107
DOI: 10.1684/mst.2019.0886 PMID: 31031233

Abstract
To determine the influence of therapeutic phlebotomy on the reduction of vaso-occlusive crises (VOCs) and of hospital admissions of patients with sickle cell disease and to describe how they experience this practice. Descriptive cross-sectional study of
27 patients with sickle cell disease who underwent phlebotomies. We estimated the number of VOCs, hemoglobin levels, and patient response. Among 27 sickle cell patients (24 SC and 3 SS) who underwent phlebotomies, there were 22 men (81.5 %) men and 5 (18.
5 %) women, with an average age of 34.6 ±10.9 years (range: 21-56 years). Before the phlebotomies, 23 (85.2 %) had showed signs of hyperviscosity, they had a mean of 5.3 ± 1.02 (range: 3-8) VOCs annually, and their mean hemoglobin level was 14.3 ±1.5g/
dl (range: 10.4 g/dl-16.8 g/dl). The mean number of phlebotomies was 4.9±4.11 (range: 1-13). After this treatment, 21 (91.3 %) reported that their signs of hyperviscosity disappeared, and the mean number of VOCs annually decreased to 0.9 ±0.07 (range:
0-2). The mean change in hemoglobin was 1.9 ±0.8 g/dl (range: 0.9-3.2 g/dl). Nine patients (6SC and 3SS), 7 under anti-anemic treatment, initially refused phlebotomy, mainly because they did not understand how it could be useful to reduce the amount of
blood in patients with a potentially anemic disease. Phlebotomy has resulted in a decrease in the frequency of VOCs and hospitalizations. It is essential to further popularize it and increase patients' aware of its value in combatting sickle cell disease
and thus improve their willingness for and adherence to this treatment.


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