In 2016, in the British Journal of Haematology, two of us wrote ‘The name of a disease entity should be specific, unambiguous and preferably short.’1 Sadly this is not always achieved. There continues to be ambiguity in the field of sickle cell disease, in submissions to journals and even in published papers. The term ‘sickle cell anaemia’ refers to a condition resulting from homozygosity for the mutation in the HBB gene that leads to glutamic acid being replaced by valine. However in some papers, particularly those referring to clinical trials, the term ‘sickle cell anaemia’ has been used to include also patients who have co-inherited sickle haemoglobin and β0 thalassaemia; these seem to be grouped together as the two commonest severe forms of sickle cell disease. We propose that, to avoid ambiguity, the term sickle cell anaemia should only be used to refer to the homozygous condition, for brevity sometimes designated, βSβS.

The term ‘sickle cell disease’ is problematical when undefined. It is correctly used to designate a group of genetic conditions with clinicopathological features resulting from the polymerisation of haemoglobin S with resultant sickling of red cells; included are not only sickle cell anaemia but also 15–20 other genotypes. Unfortunately the term is sometimes used as a synonym for sickle cell anaemia and sometimes in the broader sense. To make matters worse, it is sometimes used without being defined so that interpretation of articles becomes difficult. Conditions that can result in sickle cell disease include sickle cell anaemia, compound heterozygous states when another variant haemoglobin or β thalassaemia is co-inherited with haemoglobin S and, rarely, heterozygosity for a haemoglobin that leads to sickling in heterozygotes (Table 1).2, 3 This list of mechanisms is not exhaustive. In rare patients the variant haemoglobin coinherited with S is an unstable haemoglobin.3 In addition, coinheritance of haemoglobin S and deletional hereditary persistence of fetal haemoglobin can be asymptomatic but can also lead to quite mild sickle cell disease.3

TABLE 1. Conditions leading to sickle cell disease Category Mechanism Homozygosity for haemoglobin S (sickle cell anaemia) Polymerisation of sickle haemoglobin due to high concentration in red cells Compound heterozygosity for haemoglobin S and a β, δβ or γδβ thalassaemic condition, including thalassaemic haemoglobinopathies, haemoglobin E and haemoglobin Lepore High concentration of sickle haemoglobin in the red cell due to the relative deficit of haemoglobin A (or E or Lepore) from the thalassaemic allele Compound heterozygosity for haemoglobin S and haemoglobin C Abnormal red cell cation loss causing red cell dehydration and higher concentration of haemoglobin S Compound heterozygosity for haemoglobin S and another variant haemoglobin, including haemoglobins D-Punjab, O-Arab, S-Antilles, S-Oman, S-Wake, C-Harlem, C-Ndjamena, Quebec-Chori, O-Tibesti and Monroe Variant haemoglobin directly involved in haemoglobin polymerisation Compound heterozygosity for haemoglobin S-Antilles and haemoglobin C Red cell cation loss and dehydration, and double mutation increasing rate of polymerisation Heterozygosity for haemoglobin S-Oman, S-Antilles or Jamaica Plain Two mutations in the same beta globin allele causing haemoglobin polymerisation in heterozygotes

We strongly recommend that when the homozygous state is intended, the term ‘sickle cell anaemia’ is used, with no definition being needed. Sickle cell disease should be used generically and not as a synonym for sickle cell anaemia; the conditions included in this designation in any specific paper should be specified. When there is diagnostic uncertainty as to whether some patients have sickle cell/β0 thalassaemia or sickle cell anaemia (with microcytosis due to coexisting α thalassaemia), this should be made clear.