Advances in understanding the pathogenesis of cerebrovascular vasculopathy in sickle cell anaemia

Abstract

Cerebral vasculopathy is the most severe complication to affect children with sickle cell anaemia and its pathophysiology is complex. Traditionally, small-vessel occlusion by intravascular sickling and sludging was considered to underlie the strokes but, in the last 20 years, progressive major cerebral vessel involvement has become recognized as the principal responsible factor. Macrovasculopathy is well detected by abnormally high velocities on transcranial Doppler and with magnetic resonance angiography (MRA), and is responsible for the majority of overt strokes. Silent infarcts are ischaemic lesions detected by magnetic resonance imaging (MRI) in patients without history of stroke. They are associated with compromised cognitive functioning. The present review discusses the pathophysiologal mechanisms that could be involved in the development of cerebral vasculopathy, such as inflammation and hypoxia, anaemia, haemolysis and the resulting decreased nitric oxide bioavailability, genetic factors, impaired blood rheology and particular local haemodynamic profiles.