The pathophysiology of splenic damage is described in Chap.​ 1. Loss of splenic function can be demonstrated as early as three months of age in HbSS. On routine examination in the out-patient clinic, the spleen often enlarges sufficiently to become palpable between 6 and 18 months of age, and thereafter becomes inpalpable, atrophic and non-functional by the age of 3–5 years (Fig. 11.1). Even if the spleen continues to be palpable, or appears to be of normal size on ultrasound scan, it is likely to be hypofunctional, and we recommend that the national guidelines for protection against infection for asplenic patients should be followed for all SCD patients (See Chap.​ 12).