Hematology Case 68

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(((However it should be noted that there is some overlap in A2 percentages, particularly when co - inheritance of α thalassaemia raises the A2 percentage in βs homozygotes. There is also overlap in haemoglobin F levels, which are usually 5 – 15% in compound heterozygotes. If the red cell indices are normal, βs β0 thalassaemia can be excluded, but in patients with microcytosis the differential diagnosis is between βs βs with coexisting α thalassaemia and βs β0 thalassaemia. When a precise diagnosis is important, e.g. for genetic counselling, either family studies or DNA analysis can permit a distinction. Compound heterozygotes for βs and β+ thalassaemia are readily recognized by all techniques because of the presence of haemoglobin A.))) Barbra J. Bain, et al, Variant Haemoglobins - A giude to identification, 2010, P 37.

((( Sickle cell/β thalassaemia is a compound heterozygous state for βS and either β+ thalassaemia or β0 thalassaemia . A rare cause of an S/β0 phenotype is coinheritance of βS with deletion of the locus control region β in trans. In sickle cell/β0 thalassaemia there is no haemoglobin A, whereas in sickle cell/β+ thalassaemia a variable amount of haemoglobin A is present. The reduced concentration of haemoglobin S within the red cell, together with the greater or lesser increase in percentages of haemoglobins A2 and F, lessens the likelihood of sickling and lessens the haemolysis (in comparison with sickle cell anaemia) but this is counterbalanced by the higher Hb and increased blood viscosity.)))Barbara J. bain, Haemoglobinopathy Diagnosis, 3rd Edition, 2020, P229

(((Sickle cell/β thalassaemia; Blood count. Anaemia is milder than in sickle cell anaemia, the Hb varying from about 50 g/l to within the normal range. The distribution of Hb is bimodal, being higher in those with sickle cell/β+ thalassaemia than in those with sickle cell/β0 thalassaemia; mean values in one study were 107 and 81 g/l, respectively. The MCV, MCH and MCHC are reduced, again showing a bimodal distribution. Mean values for sickle cell/β+ thalassaemia and sickle cell/β0 thalassaemia, respectively, were 72 and 69.8 fl for MCV, 22.6 and 20.1 pg for MCH and 315 and 288 g/l for MCHC. For both groups mean values for MCV, MCH and MCHC are lower than those in sickle cell anaemia, but overlap occurs. ))) Barbara J. bain, Haemoglobinopathy Diagnosis, 3rd Edition, 2020, P230

(((Sickle cell/β thalassaemia; Haemoglobin A2 tends to be somewhat elevated, usually 3.5–5.5%, with the level being higher when the β thalassaemia gene is a β0 rather than a β+ . Higher levels of haemoglobins F and A2 (and a milder clinical course) have been observed when the β thalassaemia mutation is a large (290 bp) deletion. The higher level of haemoglobin A2 in sickle cell/β0 thalassaemia can be useful in helping to make a distinction between the compound heterozygous state and sickle cell anaemia, with microcytosis consequent on coexisting α thalassaemia trait, in which haemoglobin A2 is usually in the range of 2–4%. Although there is some overlap in haemoglobin A2 percentages this is the most useful variable for making the distinction; the Hb, reticulocyte count and haemoglobin F percentage show more overlap))) Barbara J. bain, Haemoglobinopathy Diagnosis, 3rd Edition, 2020, P230

(((Sickle cell/β thalassaemia; Diagnosis of compound heterozygosity for haemoglobin S and β+ thalassaemia is straightforward, merely requiring the demonstration of both haemoglobin A and haemoglobin S by two independent techniques and the demonstration that  haemoglobin S is present as a larger proportion than haemoglobin A. Diagnosis of compound heterozygosity for haemoglobin S and β0 thalassaemia is more difficult since a distinction has to be made from sickle cell anaemia with microcytosis e.g. due to coexisting α thalassaemia). The coexistence of α thalassaemia can lead to misdiagnosis of S/β0 thalassaemia as sickle cell anaemia ))) Barbara J. bain, Haemoglobinopathy Diagnosis, 3rd Edition, 2020, P231.