Tunisia is a part of the Mediterranean countries mostly affected by thalassemia, one of the most common genetic diseases in the world. The prevalence of TM is especially high in countries where there are close family marriages.6
Geographic distribution in this study demonstrated that TM is highly concentrated in small towns particularly in the western part of the country where there are marriages between close relatives.
Blood transfusion and iron chelation remain the cornerstone of treatment for patients with TM7
. However, there are several risks associated with chronic blood transfusions; firstly the risk of transmitting infections. In addition, long term erythrocyte transfusions inevitably lead to severe iron overload. Finally, repeated blood exposure can induce immunization, leading to difficulty in identifying compatible blood. Hepatitis C and B viruses are the most common infection agents transmitted via transfusions and routine screening is performed for these agents throughout the world. In contrast to other studies,8,9
the rate of transfusion transmitted infections with HCV is lower in our population. Alloantibodies were detected in 8.2% of our patients. These findings were in accordance with the results of Ahrens et al.5
but were lower than those reported by Singer et al.2
who reported a rate of alloimmunization of 44% among transfusion dependant thalassemia patients of predominantly Asian origin. This difference may be explained by several factors, family donation is frequently solicited in Tunisia explaining the antigenic homogeneity between donor’s antigens system and recipient’s RBC antigens. Another factor that could contribute to the low frequency found in the present study might be the early stage of the first blood transfusion for the majority of our patients. It has been thought that transfusion at an early age may offer some protection against red cell alloimmunization because of immune tolerance for young children.3,10
In the present study the most frequently detected alloantibodies were anti rhesus system. This finding is in accordance with other reported data.11,12
The prevalence of autoimmunization in multitransfused thalassemic patients in our population is high as compared to other countries. However, Bhatti et al.13
found that 1.87% of their transfusion dependant thalassemic patients developed autoantibodies. Another study in Kuwait10
reported that 11% of their patients developed autoantibodies. The higher rate found in our study may be explained by non phenotypically blood exposure in some of our patients.14
DFO was considered for a long time as the gold standard in iron chelation therapy. It has significantly improved life expectancy and the quality of life of patients with iron overload.15
But long-term management of iron overload is suboptimal in many patients, in part because of compliance issues associated with the parenteral administration regimen. Deferasirox, a once-daily oral iron chelator has proven safe and effective in reducing liver iron concentrations and serum ferritin levels in patients with various transfusion-dependant anaemia.16,17
In our study and surprisingly, treatment with Deferoxamine led to a considerable reduction of mean plasma ferritin levels when administered by subcutaneous bolus injection. However, mean plasma ferritin levels were significantly higher compared to Deferasirox when administered by pump. This might be explained by a lack of chelating treatments in some hospitals in the country and poor compliance among some of the studied patients.
Heart disease may manifest as pulmonary hypertension, arrhythmias, systolic/diastolic dysfunction, pericardial effusion, myocarditis or pericarditis. 19.8% of our studied patients, suffered from heart disease, compared with a prevalence of 15.1% reported among 566 Sicilian thalassemic patients.18
Comparison of the prevalence of cardiac involvement with other reports shows that heart failure is higher in Tunisia than in the other countries.. In a cohort of 1146 patients born from 1960 through 1987, Borgna-Pignatti et al15
found that the incidence of heart failure by 15 years of age account for 5% of the patients born between 1970 and 1974 and 2% in those born between 1980 and 1984. The reasons are not clear but are probably multiple and include less frequent transfusions, lower pre-transfusion hemoglobin level and inadequate chelation therapy.19
Iron-overload associated endocrinopathy is a frequently reported complication in chronically transfused TM patients with 60% of the patients with a dysfunction of at least one gland.20,21
These include diabetes mellitus (DM), hypogonadism, hypothyroidism, hypoparathyroidism, and low bone mass. Hypogonadotropic hypogonadism remains a common endocrinopathy in multitransfused TM patients.22
Our data are consistent with the Italian cohort in which hypogonadism was reported in nearly 50% of cases.23
In contrast, the prevalence of growth retardation was higher(26.7%) than that reported from Italy, where it is found in less than 5% of the patients.19,23
Hypothyroidism, diabetes mellitus and hypoparathyroidism are common particularly for patients in the second decade of life. Our overall diabetes rate of 4.2 % is lower than overall rate reported in Brittenham’s et al.24
cohort of 59 patients, aged 7 to 31 years. It is comparable, however, to that reported from Italy, where it is found in less than 5% of the patients25
. Mean serum ferritin level in TM patients with diabetes and those without diabetes was significantly different. However, no correlation was found between occurrence of diabetes and type chelation therapy.
Splenectomy is also beneficial in treating thalassemia major. It reduces patients’ transfusion requirement and iron overload and increases the main level of haemoglobin.26
In our study 54.0% of patients underwent splenectomy. The high number of patients who were already splenectomized at the time of the first survey might indicate that previous transfusion therapy had been inadequate in at least some of them. The risk of invasive bacterial infection in splenectomized patients is well known. Data collected by Bisharat et al.27
supports this concept. They reviewed 28 studies amounting to 6942 well-documented patients, 209 of whom developed invasive infection. Subtotal splenectomy may reduce the risk of post-splenectomy sepsis.28
Nevertheless, there are not, at the moment, specific recommendations for this procedure which has technical drawbacks in this population including regrowth of the spleen and the need for reoperation.29
Streptococcus pneumoniae was responsible for the majority of the infections (66%). It is followed for incidence by H. influenzae type b, Escherichia coli, and Neisseria meningitides. Thus prevention and treatment of bacterial infections in splenectomized thalassemic patients are life-saving measures. Splenectomized patients must receive routine vaccination, including both live attenuated and killed vaccines, but they should also be immunized against Streptococcus pneumoniae, H. influenza type b, and Neisseria meningitides. However, vaccination does not completely protect against infection with encapsulated bacteria and prophylactic antibiotics have a role as well. According to other studies, cardiac failure and rhythm disturbances remain the main causes of death among our patients.30,31
Severe anemia, if untreated, can result in high-output cardiac failure. Otherwise, cardiac failure may also result from multiple life-long transfusions. In addition infections are a frequent complication of thalassemias and they can be fatal. In our study, infections were the second cause of death after heart failure in polytransfused TM patients. Similar results were reported in Greece and in Italy.15,32
The analysis of survival rates according to chelation treatment showed that patients treated with oral chelator have a survival rate of 92.2% compared to 66.66% in patients treated with DFO. Interestingly a standard care in UHC was associated with higher rate of survival. This may be explained by several reasons mainly, lack of knowledge, difficulties in follow-up due to low-income of concerned population and unavailability of chelator. To improve the situation, public education about thalassemia is of a great importance and should be carried out through periodic meetings addressed to health professionals including doctors and nurses working in the community, and family members. Also, all means of mass media are helpful as well as the sensitization through patient parents ‘associations that facilitates the contact with families and the diffusion of information through didactic supports (brochures, booklets ect…). In reality the whole problem still lies in the difficulties in the diagnosis of abnormal hemoglobin traits and in the very limited economic resources that do not permit to take in charge correctly the numerous patients already identified. this prevention programme in Sardinia33
, the incidence of thalassaemia patients has decreased from 1:250 live births to 1:1000 live births. Similarly in Cyprus,34
the incidence of thalassaemia major cases dropped by 96%.