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

Lancet. 2003 Nov 1;362(9394):1450-5. doi: 10.1016/S0140-6736(03)14689-2.

Abstract

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 B4. Erythrocyte-endothelial adhesion and routine haematological variables were assessed. Oxygen saturation (SaO2) was measured by pulse oximetry while children were awake and asleep. Children with a mean sleeping SaO2 of < or =93% 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 SaO2 correlated only with packed-cell volume (r=0.7; p<0.0001). Inverse relations were noted between sleeping SaO2 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 SaO2 measurements showed continuing hypoxaemia, with similar correlation between SaO2 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. Further more, hypoxaemia in the older child also occurs during the day; such mild untreated hypoxia could lead to an increased risk of vaso-occlusive episodes.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Anemia, Sickle Cell / blood*
  • Anemia, Sickle Cell / complications
  • Anemia, Sickle Cell / physiopathology*
  • Biomarkers / blood*
  • Cerebrovascular Disorders / blood
  • Cerebrovascular Disorders / etiology
  • Cerebrovascular Disorders / physiopathology*
  • Child
  • Child, Preschool
  • Circadian Rhythm
  • Female
  • Hemoglobin, Sickle / metabolism
  • Hemoglobin, Sickle / physiology
  • Humans
  • Hypoxia / blood*
  • Hypoxia / physiopathology*
  • Male
  • Oximetry
  • Oxygen / blood
  • Risk Factors
  • Sleep / physiology
  • Vascular Cell Adhesion Molecule-1 / blood
  • Vascular Cell Adhesion Molecule-1 / physiology

Substances

  • Biomarkers
  • Hemoglobin, Sickle
  • Vascular Cell Adhesion Molecule-1
  • Oxygen