Anemia and ischemia: How low can you go?

In this issue of Blood, Bernaudin et al have identified the rate of acute anemic events (AAEs) and extracranial internal carotid artery (ICA) stenosis as risk factors for silent cerebral infarcts (SCIs) in children with sickle cell anemia (SCA).¹ SCIs refer to permanent brain lesions, usually small, that do not produce obvious focal neurologic deficits. These smaller strokes are often not "silent" and can cause neurocognitive impairment and poor academic performance, as well as portend overt stroke. SCIs occur as early as the first year of life, and their prevalence increases with age. About 40% of adolescents with SCA have SCIs. What causes this most frequent form of neurologic injury in SCA? Overt stroke in SCA is often preceded by occlusive cerebral arteriopathy of the large intracranial arteries, so SCIs could be caused by an arteriopathy of small vessels, but this has not been demonstrated. Vasoocclusion of small arteries and arterioles in the brain has also been proposed but has not been confirmed in humans. Critical hypoperfusion events might also cause SCIs, given that SCIs are often found in watershed regions of the brain ipsilateral to occlusive cerebral arteriopathy.