An unusual case of a spurious, transfusion-acquired haemoglobin S.

Abstract

Haemoglobin S (HbS) is caused by a point mutation in the β-globin chain (located on chromosome 11), which leads to the substitution of the hydrophilic amino acid glutamic acid by the hydrophobic amino acid valine in position six. The association of two wild-type α-globin subunits with two mutant β-globin subunits forms HbS. Under low-oxygen conditions, the lack of a polar amino acid at position six of the β-globin chain promotes the non-covalent polymerisation of deoxygenated HbS, reducing the elasticity of erythrocytes and producing the typical phenomenon of “sickling”. Sickle cells are relatively inelastic and can, therefore, occlude the microvasculature and lead to tissue infarction. Furthermore, the permanently deformed cells are removed from the circulation much earlier than normal red blood cell, which characteristically have a life span of 90 to 120 days1. Sickle cell anaemia is the disease that characterises homozygous patients with HbSS; however subjects with double heterozygosity for HbS and HbC or β-thalassaemia can have similar clinical manifestations, including moderate to severe haemolytic anaemia, increased severity of certain infections, tissue infarction with organ damage and failure, and recurrent pain episodes. This is often called sickle trait and is not associated with significant haematological abnormalities. Carriers may have episodes of haematuria and may have more urinary tract infections. Rarely, pain episodes or splenic infarctions have been observed with extreme hypoxaemia. Sudden death may be slightly more common at the extremes of human endurance2. Of the many genetic haemoglobin variants and thalassaemia syndromes identified so far, only a few have substantial clinical significance. Among these, HbS is the most common (being present in 8% of the African-American population). According to the National Institutes of Health, the overall prevalence of this inherited disorder is approximately 1 in 5,000 in the USA, with most cases being Americans of Sub-Saharan African descent, among whom the prevalence is about 1 in 500. The prevalence is also increasing in western countries and in Europe. In a recent epidemiological investigation, we showed that HbS represents the most prevalent hemoglobin variant in Northern Italy (2.8%), followed by hemoglobin C (0.7%) and E (0.4%)3. A steady increase of case notifications and hospital admissions (95% of patients are immigrants with HbS/HbS sickle cell disease) have also been observed in the same geographical area over the past 5 years4. Given these estimates, it is conceivable that some asymptomatic HbS carriers might be enrolled for regular blood donations, with the risk of causing transfusion-acquired HbS.