**2.2 Physiopathology of SCD & related secondary avascular necrosis**

Herrick first described the characteristic sickle-shaped erythrocytes in 1910 and Pauling and colleagues identified the abnormal hemoglobin (HbS) and coined the term "molecular disease" in 1949 . Hemoglobin A is normally found in the adult and is composed of four globular protein subunits the α and β globins. A fetal form or hemoglobin F is also found, normally, in small proportion in the adult. In SCD, an inappropriate substitution of valine for glutamine at the sixth position of the β globin chain produces hemoglobin S that polymerizes at low oxygen tensions. This causes the red cell to sickle which increases viscosity in the microvasculature and leads recurrent episodes of vaso-occlusion. These recurring episodes of widespread infarcts in patients homozygous for the sickle cell gene (HbSS) cause life-threatening conditions such as renal failure, acute chest syndrome, autosplenectomy, immune deficiency and infection all leading to an early death. As far as heavy surgery and especially arthroplasty is concerned in SCD patients; the key points and the difference with non SCD patients will therefore be focused into the prevention, the monitoring, and if needed, the management of the above cited acute systemic complications.

But SCD complications are not just acute; these repeated cycles of hypoxia and inflammation due to sickling cause chronic musculo-skeletal pain and finally secondary avascular necrosis of bone ends, especially, femoral and humeral heads, and less frequently, femoral condyles. This secondary avascular necrosis, at the end stages, causes severe chronic joints pain and functional impairment, for which very few solutions except of arthroplasties are currently available. In deed, secondary avascular necrosis is the leading indication of arthroplasty in SCD carriers. Secondary avascular necrosis doesn't occur only in homozygous HbSS patients; it is also common in heterozygous SCD clinically asymptomatic carriers with AS hemoglobin. In to the other hand, other types of abnormal hemoglobin such as HbC (Substitution of a lysine for glutamine at the 6th position of the β-globin chain) are also found in some patients with similar effects. Finally, secondary avasular necrosis due to SCD is therefore not exclusively observed in homozygous SS patients (HbSS); it should also be suspected in various other heterozygous forms; especially, HbAS and HbSC carriers.
