Inherited as Autosomal Recessive disease (MNEMO> Sickle Cell Disease causes Recession of RBC function)

A single DNA base change ( Beta chain) causes SCD

DNA base change is Adenine for Thymine & the resultant amino acid change is Valine for Glutamic Acid ( MNEMO> Adenine Added; Valine got a Welcome; Glutamine has to Go )

Thus Hb S is produced. As Valine is hydrophobic, the deoxygenated Hb is less water soluble and gets precipitated & polymerized inside the RBC

This polymerization slightly reduces the overall affinity for O2; otherwise the affinity for O2 is same for Hb A and Hb S

These changes also make the RBCs more rigid and contributes to sickling and microvascular occlusion

Regarding hypoxaemia, HbS will precipitate at a PO2 of 5–6 kPa (37-45 mm of Hg). As venous PO2 lies in this range, in case of homozygous individuals having only abnormal Hb will have continuous sickling

Patients with sickle cell trait experience sickling at much lower partial pressures (2.5–4 kPa / 19-30 mm of Hg )

Sickledex test produces a turbidity and becomes positive even with a very small amount of Hb S: so it CAN NOT differentiate between homo & heterozygous states

Reference: Smith T, Pinnock C, Lin T. Fundamentals of Anaesthesia, 3rd edn. Cambridge: Cambridge University Press, 2009; pp. 234–5