Clinical Picture of b- Thalassemia Major 2

Clinical Picture of b- Thalassemia Major

1.     Skeletal changes:

Un-transfused or poorly transfused patients develop typical bone abnormalities that are due to extremely increased erythropoiesis with consequent expansion of the bone marrow to 15-30 times normal. The most striking skeletal changes are seen in the skull and facial bones. There is bossing of the skull and overgrowth of the maxillary region, the whole face gradually assumes a mongloid appearance (Honig, 2000).  The outer and inner tables are thin, and the trabeculae are arranged in vertical striations, resulting in a "hair-on-end" appearance. A peculiar, stratified appearance of the skull has been reported. Ear impairment due to extramedullary marrow growing in the middle ear and progressive visual loss caused by compressive optic neuropathy have been reported (Aarabi et al., 1998).

Osteoporosis in thalassemia has been found to affect 51% of the patients, with an additional 45% affected by osteopenia. Fractures and bone pain of varying severity are common complaints among adult patients and they have been attributed to expanded bone marrow with consequent pressure on the cortical bone (Angastiniotis et al., 1998).

2.     Liver and gall bladder:

El Alfy et al., 2004 stated that during the last years, liver disease has emerged as a major cause of morbidity in patients with ß- thalassemia major (BTM). In spite of its clinical relevance, βTM- associated liver damage has been insufficiently characterized. The liver is one of the major storage sites of iron, measurement of the liver iron content (LIC) had been described as the "gold standard" for the monitoring of body iron load and for assessing the risk of iron toxicity. Modern transfusion practices in the last decade and compliance to chelation therapy are the mainstay for prevention of liver cirrhosis.

Gallstones have been reported in 4 to 23% of patients with thalassemia. The large variability may be related to differences in transfusion practices and consequent variations in ineffective erythropoiesis and hemolysis, to the time of splenectomy and, probably more importantly, to the associated presence of the (TA) 7 promoter mutation of the uridine diphosphate- glucuronosyl transferase gene, which is associated with Gilbert syndrome (Galanello et al., 2001). Intercurrent episodes of hepatitis may lead to marked liver dysfunction and contribute to development of fibrosis and cirrhosis (Masera et al., 1980).

3.     Splenomegaly and hypersplenism: 

Progressive hepatosplenomegaly is a constant finding in homozygous β-thalassaemia. There is some evidence that children maintained on a high transfusion regimen develop less marked splenomegaly. However; when children are maintained on inadequate transfusion, progressive enlargement of the spleen is the rule. Splenic enlargement may produce a variety of complications (Oliveri, 1994). There may be physical discomfort due to the size of the spleen. The formed elements of the blood may be trapped in the spleen producing anemia, thrombocytopenia and some degree of neutropenia. Trapped red cells in the splenic pool may account for 9 to 40% of the total red cell mass. Certainly in any patient with β-thalassaemia in whom there is splenomegaly with either increasing transfusion requirement or pancytopenia- the diagnosis of hypersplenism should be considered (Olivieri, 1997).

4.     Renal Complications:

Kidney involvement is related to the patient's age, severity of anemia, frequency of blood transfusion and the type of anemia. DFX has also been reported to cause renal dysfunction in these patients. Several studies have shown proximal tubular damage and tubular dysfunction with beta thalassemia major (Aldudak et al., 2000). 

5.     Thrombotic Complications:

In recent years, there have been numerous reports of, thromboembolic complications in thalassemia. In a multicenter study the frequency of thromboembolic events was found to be 4% in patients with thalassemia major and 10% in patient with thalassemia intermedia (Borgna-Pignatti et al., 1998). A chronic hypercoagulable state has been observed even in childhood (Eldor et al., 1999). Concomitant prothrombotic conditions are frequently present in thalassemia patients after the first decade of life: insulin dependent diabetes, estrogen therapy, atrial fibrillation, and postsplenectomy thrombocytosis (Eldor and Rachmilewitz, 2002).