Infections and thalassaemia

Summary

Infections are major complications and constitute the second most common cause of mortality and a main cause of morbidity in patients with thalassaemia, a group of genetic disorders of haemoglobin synthesis characterised by a disturbance of globin chain production. Thalassaemias are among the most common genetic disorders in the world. Predisposing factors for infections in thalassaemic patients include severe anaemia, iron overload, splenectomy, and a range of immune abnormalities. Major causative organisms of bacterial infections in thalassaemic patients are Klebsiella spp in Asia and Yersinia enterocolitica in western countries. Transfusion-associated viral infections (especially hepatitis C) can lead to liver cirrhosis and hepatocellular carcinoma. A unique and challenging infection detected in Asian patients is pythiosis, caused by a fungus-like organism, the mortality rate of which is very high. Because the prognosis for thalassaemia has much improved, with many patients surviving to the fifth decade of life in developed countries, it is mandatory to reduce mortality by recognising and presumptively treating infections in these patients as quickly as possible.

Introduction

The term thalassaemia (derived from the Greek “thalassa”, which means “the sea”—referring to the Mediterranean—and “emia”, meaning “related to blood”) indicates a heterogeneous group of genetic disorders of haemoglobin synthesis characterised by a disturbance of the production of globin chains, leading to anaemia, ineffective erythropoiesis, and destruction of erythroblasts in the bone marrow and of erythrocytes in the peripheral blood.¹ In individuals that produce normal haemoglobin, two types of polypeptide chains (α and non-α) pair with each other at a ratio close to 1/1 to form normal haemoglobin molecules. In thalassaemic patients, an excess of the normally produced type accumulates in the cell as an unstable product, leading to the destruction of the cell. This imbalance is the hallmark of all forms of thalassaemia. Types of thalassaemia are usually named after the underproduced chain or chains.

Thalassaemias are found in all parts of the world, and the often used name “Mediterranean anaemia” is misleading. α-Thalassaemia may be the most common single gene disorder in the world (percentage of gene carriers in the middle east is 5–10%, 20–30% in west Africa, and up to 68% in the South Pacific), although the gene prevalence in northern Europe and Japan is less than 1%.¹ In β-thalassaemia, the frequency of the gene is greater than 1% in the Mediterranean basin, India, southeast Asia, north Africa, and Indonesia (figure).⁴

Clinical severity varies widely, ranging from asymptomatic forms to severe or even fatal entities. In the severe forms of thalassaemia—eg, Cooley's anaemia or thalassaemia major—the large numbers of abnormal red blood cells processed by the spleen and its haematopoietic response to the anaemia lead to massive splenomegaly and consequent manifestations of hypersplenism, resulting in the need for splenectomy. If chronic anaemia in thalassaemic patients is corrected with regular blood transfusions (with the aim of maintaining the pretransfusional haemoglobin concentration at 9 g/dL or higher), another source of iron is added, which, together with the excessive iron absorption normally present in such cases, leads to a state of iron overload. Iron accumulates in various organs, especially in the heart and the liver, resulting in substantial damage. Morbidity in patients with severe thalassaemia is usually the result of iron-related heart failure, serious infections, or the complications of splenectomy. Bloodborne viral infections (mainly hepatitis C and B), infections with unusual organisms whose presence is favoured by iron overload or by the chelation therapy needed to reduce it, and post-splenectomy infections all contribute substantially to morbidity and mortality in thalassaemic patients, making infections the second most common cause of death after heart failure.⁵