Sickle Cell Disease Sickle cell disease is a common haemolytic disorder in black races. It is due to the presence of HbS, caused by a single base mutation from adenine to thymine. This produces a substitution of valine for glutamine at the 6 th codon of the - globin chain. In the homozygous state both -chains are abnormal, whereas in the heterozygous state only one chromosome is abnormal, and the disease is much less severe. HbF is normal.
Haemoglobin Normal adult Hb (HbA) consists of 2 and 2 polypeptide globin chains. These fold in a quaternary structure to enfold a haem group. Hb S is less soluble than Hb A and, when deoxygenated, undergoes polymerisation, leading to the formation of sickle shaped cells.
Symptoms in Sickle cell disease: Vascular occlusion due to sickle cells lodging in capillaries. This can occur in any part of the body, causing a “sickle crisis”. Typically these can cause bone pain, pleuritic pain, cerebral infarcts, priapism and hepatic pain with fever. Long term complications can occur, including susceptibility to strp. Pneumoniae infection, chronic leg ulcers, aseptic necrosis of bone, blindness and chronic renal disease. Gallstones occur from pigment due to persistent haemolysis.
Investigations A full blood count: Hb 6-8g/dl with high reticulocyte count. Blood film: Sickling of rbcs induced by sodium metabisulphite. Sickledex is a commercial test where sodium dithionite gives a turbid appearance to HbS, wheras normal Hb remains clear. Hb electrophoresis. No HbA, 80-95% Hb SS, 2-20% HbF
treatment Maintain hydration with IV fluids, oxygen via face mask analgesia, usually with opiates. Consider underlying cause, such as sepsis. Priapism may be treated with normal saline washouts of corpora cavernosa and direct injection with adrenergic agent, such as methoxamine or phenylephrine (unlicenced).
Classification of anaemia: 1.Haemolytic- blood cells breaking up 2.Aplastic- blood cells not being made 3.Blood loss
Haemolytic Disease: congenital Sickle cell: may get sickle “Trait” of heterozygous form. OK unless stressed in oxygen requirements e.g scuba diving, GA Spherocytosis: autosomal dominant G6PD deficiency (fava beans)