Choice of the Scheme for Blood Transfusion in Thalassemia Major:

Choice of the Scheme for Blood Transfusion in Thalassemia Major:

-         Intermediat schemes:

Mean Hb 9-10 gm/dL are acceptable in terms of daily living, they may have to be accepted in areas where the blood supply is inadequate (Cazzola et al., 1997).

-         Hypertransfusion schemes :

Mean Hb 10 gm/dL or greater. Improve the quality of life without accelerating the lethal complications of iron overload, also suppress erythroid activity and prevent the unlimited bone marrow expansion that underlies the skeletal pathology of thalassemia major. Additional advantages of a regular transfusion program include prevention or delay in the development of congestive splenomegaly and fewer severe infectious illnesses (Lukens, 1993).

-         Supertransfusion program:

Stabilizes Hb levels at 11 to 12 gm/dL. Hemoglobin value is never allowed to drop below 12 gm/dL and is raised regularly to 14 gm/dL by small transfusion every 2-3 weeks. Super-transfusion permits an excellent quality of life and suppression of the bone marrow so that abnormal cells are cleared from the peripheral blood (Model and Berdoukas,, 1984).

Chelation Therapy:

There is no doubt that the judicious use of chelation has been one of the most effective therapeutic advances in prolonging life of thalassemia patients (Deborash and Elizer, 2000). Patients who begin treatment at a young age can be protected from the lethal complications of iron overload for at least two decades. Those persons with established heart and other organ dysfunction may experience an arrest of disease progression or improvement of function with intense chelation (Cohen, 2006).

a.     Subcutaneous Iron Chelators:

-         Desferrioxamine:

Desferoxamine B atrihydroxamic acid produced by streptomyces pilosus, with relative specificity for ferric iron. Desferoxamine is poorly absorbed from the gastrointestinal tract and has an extremely short half–life and thus it must be administered parenterally, usually a continuous subcutaneous infusion in a dose of 25-50 mg/kg given over 8-12 hours 5-7 days per week (Kwiatkowski, 2008).

Improvement in Prognosis and Survival

Improvement in Prognosis and Survival

Historically, patients who had thalassemia had a poor prognosis. In a United States cohort born between 1960 and 1976, the median was 17 years (Ehler et al., 1991). Remarkable and promising improvement in survival of patients who have thalassemia has been made (Borgna-Pignatti, 2004). The prognosis of patients with homozygous B-thalassemia major has been improved by transfusion and iron-chelation therapy. Prognosis for survival without cardiac disease is excellent for patients who receive regular transfusions and whose serum ferritin concentrations remain below 2500 ng per milliliter with chelation therapy (Borgna-Pignatti, 2004).

Table (1):    Causes of death in patients with β –Thalassemia

Cause of Death	Percentage of people with thalassemia major
Heart problems: -          Heart failure -          Irregular heart rhythm  -          Heart attack	60% 7% 2%
Infection	7%
Liver cirrhosis	4%
Thrombosis (blood clot in brain, lungs or heart)	4%
Cancer	4%
Diabetes	3%
Unknown causes	3%
Other (e.g., accidents, renal failure, HIV/AIDS, anemia)	7%

Management of β-Thalassemia Major

Red cell transfusion

Regular red cell transfusion eliminates the complications of anaemia and ineffective erythropoiesis, permit normal growth and development throughout childhood and extend survival in thalassemia major (Oliverri et al., 1997). 6-8 cc/Kg of PRBC’s at 2-3 weekly intervals decreases the yearly iron load by 20% (Spanos at al., 1995). The goal of long-term hypertransfusional support is to maintain the patient's Hb at 9-10 g/dL, thus improving the patient's sense of  well-being  simultaneously.

Progress in prenatal diagnosis:

Polymerase-chain-reaction (PCR) technology has been used for more than a decade to detect point mutations or deletions in chorionic-villus samples, enabling first–trimester, DNA-based testing for thalassemia. However, because pregnancy termination is unacceptable to some persons (even when the fetus is affected), methods were developed, beginning in the early 1990s, to perform diagnostic testing before implantation (Rund and Rachmilewitz, 2005). PCR is then used to detect thalassemia mutations within the cells that have been removed so that unaffected blastomeres may be selected for implantation. Preimplantation genetic diagnosis requires a high degree of technical expertise. Furthermore, the phenomenon of "allele dropout"; failure to amplify one of the two alleles in a heterozygous cell can result in diagnostic errors. Nonetheless, this technology has been successful, and improvements in outcome have led to its use in many countries  (van de velde et al., 2004). Recently, preimplantation genetic diagnosis has been extended to HLA typing on embryonic biopsies, which allows the selection of an embryo that is not affected by thalassemia and that may also serve as a stem-cell donor for a previously affected child within the same family (Rund and Rachmilewitz, 2005).

Although it is considered ethical not to implant an embryo that is affected with a serious genetic disorder, in certain countries it is forbidden to select an embryo on the basis of its designated role as a potential stem-cell donor. Future prenatal diagnosis may to be performed non –invasively, with the use of maternal blood samples to isolate either fetal cells or fetal DNA for analysis (Di Naro et al., 2002).

Imaging studies:

Imaging studies:

The classic appearance of the skull, which results from widening of the diploic spaces, is observed on plain radiographs. Maxilla may overgrow, which results in maxillary overbite, prominence of the upper incisors, and separation of the orbits. These changes contribute to the classic "chipmunk facies" observed in patients with thalassemia major (Atichartakarn et al., 2003).

Compression fractures and paravertebral expansion of extramedullary masses, which could behave clinically like tumors, more frequently occur during the second decade of life. MRI and CT scanning are usually used in diagnosing such complications and can be used as noninvasive means to evaluate the amount of iron in the liver in patients receiving chelation therapy (Fucharoen et al., 2000).

Hepatic iron concentration by liver biopsy:

It is considered the most accurrate and sensetive method for determining the body iron burden. However, this is an invasive technique with a low but recognized complication rate; the result is affected by hepatic fibrosis (especially in small biopsy) which is common in thalassemia as a result of increased liver iron and HCV infection; and the iron has been shown to be unevenly distributed in the thalassemic liver even in the non cirrhotic stages (Cohen et al., 2004).    

Other Tests:

·        ECG and echocardiography are performed to monitor cardiac function.

·        HLA typing is performed for patients for whom bone marrow transplantation is considered.

·        Eye examination.

·        Hearing tests.

·         Renal function tests are required to monitor desferroxamine therapy.

·        Routine endocrine tests.

·        Screening for hepatic dysfunction (Honig, 2000).