Hypoxaemia in sickle cell disease: biomarker modulation and relevance to pathophysiology

Background Nocturnal oxyhaemoglobin desaturation might have a role in CNS complications related to sickle cell disease, and rates of painful crises. We attempted to examine the biological relations, and describe the haematological risk factors for oxyhaemoglobin desaturation. Methods The study population included children with sickle cell disease and controls. Cellular activation was assessed by measurement of soluble vascular cell adhesion molecule 1, P-selectin, L-selectin, and leukotriene B-4. Erythrocyte-endothelial adhesion and routine haematological variables were assessed. Oxygen saturation (SaO(2)) was measured by pulse oximetry while children were awake and asleep. Children with a mean sleeping SaO(2) of less than or equal to93% were identified as hypoxaemic. Children were divided into four groups: controls (ten children), HbSC (nine, all normoxic), HbSS normoxic (13), and HbSS hypoxaemic (15). Findings Among haematological variables, sleeping SaO(2) correlated only with packed-cell volume (r=0.7; p<0.0001). Inverse relations were noted between sleeping SaO(2) and adhesion (-0.45; p<0.01), and markers of white-cell (-0.51; p<0.01), platelet (-0.61; p<0.001), and endothelial activation (-0.46; p<0.01). In the HbSS group who had sleeping hypoxaemia, waking SaO(2) measurements showed continuing hypoxaemia, with similar correlation between SaO(2) and cell activation markers. Interpretation: Our adhesion-related findings suggest a potential mechanism for the increased occurrence of clinical vaso-occlusive crises in individuals with sickle cell disease who have oxyhaemoglobin desaturation. Release of cellular mediators in hypoxaemia, and the relation between anaemia and oxyhaemoglobin desaturation, suggest that risk factors for stroke, including anaemia, might have a role in CNS-vasculopathy through hypoxia-mediated pathways. Furthermore, hypoxaemia in the older child also occurs during the day; such mild untreated hypoxia could lead to an increased risk of vaso-occlusive episodes.