474 q 2000 Blackwell Science Ltd Platelet and leucocyte activation in childhood sickle cell disease: association with nocturnal hypoxaemia David P. Inwald, 1,2 Fenella J. Kirkham, 3 Mark J. Peters, 1,2 Rod Lane, 1 Angie Wade, 3 Jane P. Evans 4 and Nigel J. Klein 2 1 Portex Unit of Anaesthesia, Intensive Care and Respiratory Medicine, 2 Immunobiology Unit, 3 Neurosciences Unit, 4 Department of Epidemiology and Biostatistics, Institute of Child Health, and 5 Department of Haematology, Great Ormond Street Hospital for Children NHS Trust, London, UK Received 23 April 2000; accepted for publication 21 June 2000 Summary. We hypothesized that vaso-occlusive events in childhood sickle cell disease (SCD) may relate to inflamma- tory cell activation as well as interactions between sickle erythrocytes and vascular endothelium. Peripheral blood was examined from 24 children with SCD, of whom 12 had neurological sequelae and seven had frequent painful crises, and 10 control subjects. Platelet (CD62P and CD40L expression) and granulocyte (CD11b expression) activation and levels of platelet±erythrocyte and platelet±granulocyte complexes were determined by flow cytometry. Platelets (P  0´019), neutrophils (P  0´02) and monocytes (P  0´001) were more activated and there were increased platelet±erythrocyte complexes (P  0´026) in SCD patients compared with controls. Platelet±granulocyte complexes were not raised. There were no differences between the different groups of SCD. As hypoxia activates monocytes, platelets and endothelial cells and causes sickling of SCD erythrocytes, we also investigated 20 SCD patients with overnight pulse oximetry. Minimum overnight satura- tion correlated with the level of platelet±erythrocyte complexes (Spearman's r 20´668, P , 0´02), neutrophil CD11b (Spearman's r 20´466, P  0´038) and monocyte CD11b (Spearman's r 20´652, P  0´002). These findings provide important clues about the mechanism by which SCD patients may become predisposed to vaso-occlusive events. Keywords: platelets, granulocytes, activation, sickle cell disease, hypoxaemia. Vascular occlusion is an important cause of morbidity and mortality in sickle cell disease (SCD), causing painful crises, pulmonary, hepatic and splenic sequestration, sickle nephro- pathy and stroke. Frequent pain, defined as at least two episodes per year in childhood (Miller et al, 2000), is a significant burden for the patient. Stroke is one of the most devastating consequences of SCD and has an incidence of 8±12%, which peaks in childhood (Powars et al, 1978; Balkaran et al, 1992; Ohene-Frempong et al, 1998). The only method of secondary prevention of stroke in SCD is regular transfusion and current clinical practice following stroke is transfusion to keep the HbS concentration below 30% (Pegelow et al, 1995). Primary prevention may be achieved by transfusing those with high velocities on transcranial Doppler (Adams et al, 1998). Understanding the pathophysiology of vascular occlusion might lead to earlier preventative strategies with less adverse effects and greater patient acceptability. Recent observations that sickle erythrocytes are inherently adhesive to the vascular endothelium (Hebbel, 1997) and that vascular endothelial cells (Solovey et al, 1997, 1998), neutrophils (Fadlon et al, 1998; Lard et al, 1999) and platelets (Wun et al, 1998) are activated in adults with SCD suggests that acute and chronic vascular occlusion may be dependent on enhanced cellular adhesiveness and inflammatory cell activation, as well as on mechanical obstruction by abnormal sickle erythrocytes (Kaul et al, 1986). In this study, we aimed to explore the hypothesis that inflammatory cells in children with SCD differ in their capacity for cellular adhesion from controls. We looked for differences in cellular adhesion between children with SCD with neurological sequelae or frequent pain and children with SCD alone. We have previously observed a strong association between nocturnal hypoxaemia and subsequent central nervous system (CNS) events (Kirkham et al, 1997) and the number of painful crises requiring hospitalization (Hargrave British Journal of Haematology , 2000, 111, 474±481 Correspondence: Dr D. P. Inwald, Institute of Child Health, 30 Guilford Street, London WC1N 1EH. UK. E-mail: d.inwald@ich. ucl.ac.uk