Pulmonary infarction in disorders associated with the sickle cell trait.

The disorders associated with the sickle cell trait have not, in the past, been seen very often in Britain because they are largely confined to the Negro race. However, increased immigration from the West Indies, where the trait can be found in about 10% of the Negro population (Tomlinson, 1945), has made the recognition of these diseases more important in this country (Diamond, 1959). The sickle cell disorders are the result of the inheritance of a dominant gene. This gene determines the presence of an abnormal haemoglobin, haemoglobin S. The abnormal haemoglobin in its reduced state is insoluble and readily crystallizes to produce the characteristic distortion of the red cell. In the homozygous individual 75-100% of red cell haemoglobin will be haemoglobin S, when the severe disease known as sickle cell anaemia develops and death in childhood or early adult life is the usual fate. This is said to occur in about 3% of all those who carry the gene. If the genetic constitution is heterozygous, sickle cell trait (haemoglobin S) will constitute 25-50% of the haemoglobin in the red cell and there is usually slight or no clinical disability, except in unusual circumstances, but " manifestations of sickle cell disease such as bone infarction, haematuria, infarction of the spleen and haemolytic anaemia have been recognized with increasing frequency in individuals with sickle cell trait" (Smith and Krevans, 1959). There are other abnormal haemoglobins, such as haemoglobin C, which are inherited in the same way, and thalassaemia is the result of the inheritance of a gene which suppresses the formation of normal haemoglobin A and leads to the persistence of the foetal type, haemoglobin F. If any of these traits be combined in a heterozygous subject with the sickle cell trait, then clinical syndromes similar to that of sickle cell anaemia may occur. Sickling of red cells has two effects; the distorted cells have a short survival time which leads to anaemia of haemolytic type, and they may cause vascular obstruction by blocking small blood vessels or provoking thrombosis in larger vessels because of their increased viscosity. Sickling develops when haemoglobin S is reduced by deoxygenation and the effect is potentiated by lowering of blood pH. Sickle cells are therefore more common in the venous side of the systemic circulation than the arterial. Sherman (1940) in cases of homozygous SS sickle cell disease found 40-60% of red cells in the sickled state in blood obtained by venepuncture and only 5-20% partially sickled in blood drawn from an artery. Sickle cells will be relatively common in the mixed venous blood in the pulmonary arteries, and, as the distortion of the red cell is not an instantaneous response to deoxygenation, the small vessels of the pulmonary circulation may be the first vessels of narrow lumen that the abnormal erythrocytes meet. Pulmonary arterial obstruction with pulmonary infarction has been described by pathologists as a common post-mortem finding in fatal cases of sickle cell anaemia (Steinberg, 1930; Bauer, 1940), but even in the U.S.A. where the sickle cell trait is common there have been few reports of this condition diagnosed in life (Mallory, 1941 ; Moser and Shea, 1957). In Britain, pulmonary infarction as a complication of the sickle cell trait has not previously been reported.