You will also have regular blood tests and physical exams. It is important to avoid infections. Wash your hands often and avoid others who are sick. You may also need emotional support.
Talk with your provider. He or she can help you find support. Different people will have different symptoms, based on which type of beta thalassemia is inherited. Health Home Conditions and Diseases.
What causes beta thalassemia? This type is further divided into: Thalassemia minima: There are few or no symptoms. Thalassemia intermedia: This causes moderate to severe anemia. Who is at risk for beta thalassemia? What are the symptoms of beta thalassemia? Different people will have different symptoms, based on which type of the disorder is inherited. Children born with this type will have symptoms early in life that include: Pale skin Fussy Having a poor appetite Having many infections Over time more symptoms will appear, including: Slowed growth Belly abdominal swelling Yellowish skin jaundice Without treatment, the spleen, liver, and heart become enlarged.
Thalassemia minima: This type often causes no symptoms. Thalassemia intermedia: This type can cause symptoms of moderate to severe anemia including: Extreme tiredness fatigue Pale skin Slow or delayed growth Weak bones Enlarged spleen How is beta thalassemia diagnosed? These tests may be able to tell if you are a carrier, and can pass the disorder on to your children: Complete blood count CBC : This test checks the size, number, and maturity of different blood cells in a set volume of blood.
How is beta thalassemia treated? Your healthcare provider will figure out the best treatment based on: Your age, overall health, and medical history How sick you are How well you can handle certain medicines, procedures, or therapies How long the condition is expected to last Your opinion or preference Treatment may include: Regular blood transfusions Medicines to reduce extra iron from your body called iron chelation therapy Surgery to remove the spleen, if needed Daily folic acid Surgery to remove the gallbladder Regular checks of heart and liver function Genetic tests Bone marrow transplant Note: Do not take any iron supplements.
Despite this, serial measurements of serum ferritin remain a reliable and the easiest method to evaluate iron overload and efficacy of chelation therapy. Determination of liver iron concentration in a liver biopsy specimen shows a high correlation with total body iron accumulation and is considered the gold standard for the evaluation of iron overload [ 38 ].
However, liver biopsy is an invasive technique with the possibility though low of complications. Moreover, we should consider that the presence of hepatic fibrosis, which commonly occurs in individuals with iron overload and HCV infection, and heterogeneous liver iron distribution can lead to possible false negative results [ 39 ]. In recent years, nuclear magnetic resonance imaging MRI techniques for assessing iron loading in the liver and heart have been introduced [ 40 - 43 ]. Magnetic biosusceptometry SQUID , is another option for a reliable measurement of hepatic iron concentration [ 46 ]; however, magnetic susceptometry is presently available only in a limited number of centers worldwide.
The first drug available for treatment of iron overload was deferoxamine DFO , an exadentate iron chelator that is not orally absorbed and thus needs parenteral administration, usually as a subcutaneous 8- to hour nightly infusion, nights a week.
Implanted delivery systems are associated with risk of thrombosis and infection. The most frequent adverse effects of DFO are local reactions at the site of infusion, such as pain, swelling, induration, erythema, burning, pruritus, wheals and rash, occasionally accompanied by fever, chills and malaise.
Other complications, mainly associated with high doses of DFO in young patients and low ferritin values are:. It is therefore important to monitor patients receiving DFO regularly with audiometric and ophthalmologic tests and with regular evaluation of growth and bone changes. The use of DFO decreases morbidity and mortality among those who are able to comply with regular prolonged infusions [ 47 ].
However, because of the side effects and the inconvenient parenteral administration, a consistent proportion of patients is non-compliant, limiting the usefulness of this chelator [ 35 ]. The orphan drug deferiprone DFP is an orally active iron chelator which has emerged from an extensive search for new treatment of iron overload. Retrospective and prospective studies have shown that DFP monotherapy is significantly more effective than deferoxamine in decreasing myocardial siderosis in thalassemia major [ 49 - 51 ].
More common but less severe side effects are gastrointestinal symptoms, arthralgia, zinc deficiency, and fluctuating liver enzymes. Retrospective studies have shown that DFP treatment is associated with reduced cardiac morbidity and mortality [ 50 , 52 , 53 ].
DFO and DFP can be used in combination to achieve levels of iron excretion that cannot be achieved by either drug alone without increasing toxicity [ 54 - 59 ]. Reversal of severe iron-related heart failure with DFO and DFP combination has been reported in many patients [ 44 , 60 - 62 ]. Combination therapy should be considered as an alternative to continuous intravenous DFO monotherapy when an intensive chelation is required.
Deferasirox DFX is a once-daily, orally administered iron chelator that a large program of clinical trials has shown to be effective in adults and children [ 64 , 65 ]. It received European Union marketing authorization as an orphan drug from the EMEA in and was authorized for marketing in most countries in The most frequent adverse events reported during treatment with DFX include transient, mild-to-moderate gastrointestinal disturbances and skin rash.
These events rarely require drug discontinuation and most resolve spontaneously. Mild, usually nonprogressive increases in serum creatinine generally within the upper limit of normal has been observed in approximately a third of patients. Creatinine levels returned spontaneously to baseline in most of patients and data from up to 3.
However, cases of renal failure have been reported following the postmarketing use of DFX [ 67 ]. S -3'- OH -desazadesferrithiocin-polyether, magnesium salt is an oral once a day iron chelator expected to excrete iron mainly in the stools, evaluated in experimental models. Orphan designation of this medicine has been granted in the United States of America and Europe for treatment of chronic iron overload in patients with transfusion-dependent anemias.
Recently, three main practice guidelines for the management of iron overload in thalassemia major have been published and are available online [ 3 , 68 , 69 ]. Studies evaluating the secretion of growth hormone GH in patients with thalassemia major have yielded contradictory results, limiting the therapeutic use of GH to those patients proven to have GH deficiency, who may have a satisfactory response to treatment [ 70 - 72 ].
In cases with signs of bone toxicity from DFO a reduction of the dose, or its substitution with an oral chelator, can prevent progression of bone lesions and improve growth. For delayed puberty in girls, therapy may start with the administration of ethinyl estradiol 2. If breakthrough uterine bleeding does not occur, a low oestrogenprogesterone hormone replacement is recommended.
For delayed puberty in males, intramuscular depot-testosterone esters at a dose of mg twice a month should be given, until complete virilisation has been achieved [ 72 ]. Topical testosterone gel can also be used [ 73 ]. When there is a lack of pubertal progression over a year or longer arrested puberty , testosterone esters in males and oestrogenprogesterone replacement therapy in females is indicated. In males suffering from azoospermia or asthenospermia and asking for fertility treatment, spermatogenesis may be induced by combination therapy with hCG human chorionic gonadotrophin and hMG human menopausal gonadotrophin intramuscularly or subcutaneously.
Moreover, the recent advent of micromanipulation techniques such as intracytoplasmatic sperm injection ICSI has improved conception rates. Females with thalassemia may have primary or secondary amenorrhea, which leads to failure of the reproductive axis with chronic anovulation. Despite severe hemosiderosis, ovarian function is preserved in most patients, and they are still able to increase the estradiol level following stimulation with gonadotrophins, and furthermore produce ova.
Induction of ovulation must be performed under rigorous control after a global evaluation of the patient, including detailed assessment of heart, liver function, viral infections, endocrinopathies, with particular emphasis on diabetes control and thrombophilia status [ 74 ].
Pregnant patients with thalassemia need a multidisciplinary approach involving all specialists in the medical care of thalassemia [ 75 ]. A careful follow-up with an intensification of chelation therapy is required in such cases. It is debatable whether patients with subclinical hypothyroidism should be treated. If treatment is considered unnecessary, close monitoring is mandatory. In overt hypothyroidism, characterized by low T4 and FT4 values with signs and symptoms such as mental and physical sluggishness, weight gain, feeling of cold, sleepiness, bradycardia and constipation, treatment with increasing doses of L-thyroxine starting with 25 mg per day is indicated.
Abnormal thyroid function may be reversible at an early stage through intensive combined chelation [ 76 ]. Severe hypocalcemia with tetany requires intravenous administration of calcium under careful electrocardiographic monitoring, followed by oral vitamin D. In milder forms, calcitriol is the drug of choice, because of its short half-life and rapid action. A dosage of 0. Because of the risk of hypercalcemia and hypercalciuria, serum calcium level and hour urinary calcium and phosphate measurements should be carefully monitored, especially at the beginning of treatment and if elevated doses of Vitamin D are administered.
Acarbose at the dose of mg orally with breakfast, lunch and evening meals has been used with good results for impaired glucose tolerance or non-insulin dependent diabetes mellitus and hyperinsulinism [ 77 ]. Patients with diabetes mellitus, may require daily subcutaneous injections of insulin. Since treatment of diabetes in patients with thalassemia major is an additional burden, support from doctors and psychologists is needed.
Investigation of the kidney function and imaging of the fundi should be carried out to evaluate the presence and degree of diabetic complications. Intensive iron chelation therapy with DFO and DFP seems to be associated with an improvement in glucose intolerance in terms of glucose and insulin secretion, particularly in patients in early stages of glucose intolerance [ 78 ].
Since osteoporosis is a progressive disease, prevention is the basis of the management. No smoking, a calcium-rich diet, correction of hypogonadism by sex hormone replacement therapy and regular exercise should be recommended. Oral calcium supplements should be used with caution because of the risk of renal stones.
Several bisphosphonates have been used in thalassemia patients for the treatment of osteoporosis with variable results. To date, alendronate, pamidronate, and zoledronate seem to be effective in increasing bone mineral density and normalizing bone turnover, but more controlled trials are necessary to evaluate their efficacy in reducing fracture risks in larger thalassemic populations [ 79 ].
Bone marrow transplantation BMT remains the only definitive cure currently available for patients with thalassemia.
The outcome of BMT is related to the pretransplantation clinical conditions, specifically the presence of hepatomegaly, extent of liver fibrosis, history of regular chelation and hence severity of iron accumulation. The major limitation of allogenic BMT is the lack of an HLA-identical sibling donor for the majority of affected patients.
BMT from unrelated donors has been carried out on a limited number of individuals with beta-thalassemia. Provided that selection of the donor is based on stringent criteria of HLA compatibility and that individuals have limited iron overload, results are comparable to those obtained when the donor is a compatible sib [ 81 ].
However, because of the limited number of individuals enrolled, further studies are needed to confirm these preliminary findings. If BMT is successful, iron overload may be reduced by repeated phlebotomy, thus eliminating the need for iron chelation.
Cord blood transplantation from a related donor offers a good probability of a successful cure and is associated with a low risk of GVHD [ 82 , 83 ]. For couples who have already had a child with thalassemia and who undertake prenatal diagnosis in a subsequent pregnancy, prenatal identification of HLA compatibility between the affected child and an unaffected fetus allows collection of placental blood at delivery and the option of cord blood transplantation to cure the affected child [ 84 ].
On the other hand, in cases with an affected fetus and a previous normal child, the couple may decide to continue the pregnancy and pursue BMT later, using the normal child as the donor. Treatment of individuals with thalassemia intermedia is symptomatic [ 4 , 85 ].
As hypersplenism may cause worsening anemia, retarded growth and mechanical disturbance from the large spleen, splenectomy is a relevant aspect of the management of thalassemia intermedia. Risks associated with splenectomy include an increased susceptibility to infections mainly from encapsulated bacteria Streptococcus Pneumoniae, Haemophilus Influenzae and Neisseria Meningitidis and an increase in thromboembolic events.
Prevention of post-splenectomy sepsis includes immunization against the above mentioned bacteria and antibiotic prophylaxis as well as early antibiotic treatment for fever and malaise. Because of the elevated prevalence of cholelithiasis and the risks of cholecystitis in splenectomised patients, the gallbladder should be inspected during splenectomy and removed in case with or to prevent gallstones.
Treatment of extramedullary erythropoietic masses, detected by magnetic resonance imaging, is based on radiotherapy, transfusions, or hydroxycarbamide.
Once leg ulcer has developed, it is very difficult to manage. Regular blood transfusions, zinc supplementation and pentoxifylline, and the use of an oxygen chamber have been proposed for ulcer treatment.
Hydroxycarbamide also has some benefit, either alone or with erythropoietin. Recently promising results have been obtained with platelet derived growth factor. Since patients with thalassemia intermedia have a high risk of thrombosis, exacerbated by splenectomy, it is important to be aware of thrombotic complications. Supplementary folic acid can be prescribed to patients with thalassemia intermedia to prevent deficiency from hyperactive bone marrow.
If the disease is fully compensated by ideal treatment, an individual with thalassemia major can enjoy a near-normal lifestyle and experience normal physical and emotional development from childhood to adulthood, including parenthood.
Patients with thalassemia do not have specific dietary requirements, unless they have special prescriptions. Patients already have a heavy treatment schedule and it is counterproductive to add further restrictions without the likelihood of clear benefit.
During growth, a normal energy intake with normal fat and sugar content is recommended. During adolescence and adult life, a diet low in highly refined carbohydrates may be useful in preventing or delaying the onset of impaired glucose tolerance or diabetes. There is no clear evidence that a specific diet is beneficial in preventing or managing liver disease, unless at late stages. Increased iron absorption from the intestinal tract is characteristic of thalassemia. The amount depends on the degree of erythropoiesis, the Hb level and other potential independent factors.
Drinking a glass of black tea with meals reduces iron absorption from food, particularly in thalassemia intermedia [ 85 ]. However, there is no evidence that iron-poor diets are useful in thalassemia major; only foods very rich in iron such as liver, many baby foods, breakfast cereals and multivitamin preparations contain added iron, along with other vitamin supplements should be avoided.
Since many factors in thalassemia promote calcium depletion, a diet containing adequate calcium e. However, nephrolithiasis is seen in some adults with thalassemia major, and calcium supplements should not be given unless there is a clear indication; instead a low oxalate diet should be considered. Patients with thalassemia who remain untransfused or are on low transfusion regimens have increased folate consumption and may develop a relative folate deficiency.
Patients on high transfusion regimens rarely develop this condition, and usually have no need for supplements. Iron overload causes vitamin C to be oxidized at an increased rate, leading to vitamin C deficiency in some patients. Vitamin C may increase iron absorption from the gut, labile iron and hence iron toxicity and may therefore be particularly harmful to patients who are not receiving DFO, as iron mobilized by the vitamin C will remain unbound, causing tissue damage.
The effectiveness and safety of vitamin E supplementation in thalassemia major has not been formally assessed and it is not possible to give recommendations about its use at this time.
Patients with thalassemia should be discouraged from consuming alcohol, as it can facilitate the oxidative damage of iron and aggravates the effect of HBV and HCV on liver tissue. In general, physical activity must always be encouraged unless there is a precise secondary medical condition.
Conditions requiring special attention include splenomegaly, severe heart disease and osteoporosis. There is no reason for patients with thalassemia to skip or delay standard recommended vaccinations. To prevent and minimize the risk of infection, immunization with the pneucococcal, Haemophilus Influenza and meningococcal vaccines is recommended about two weeks before splenectomy and after surgery.
It is now universally recognized that thalassemia, like other chronic diseases, has important psychological implications. A key role for treating physicians and other health care professionals is to help patients and families to face up to the difficult demands of treatment, while maintaining a positive role.
Induction of HbF synthesis can reduce the severity of beta-thalassemia by improving the imbalance between alpha and non-alpha globin chains. Several compounds including 5-azacytidine, decytabine, and butyrate derivatives gave encouraging results in clinical trials [ 87 ]. These agents induce Hb F by different mechanisms not yet well defined. Their potential in the management of beta-thalassemia syndromes is under investigation. Many patients with beta-thalassemia require life-long, regular blood transfusions transfusion-dependent thalassemia and may present a range of health complications, including iron overload, which can result in damage to the heart, liver and endocrine system.
Southern Mediterranean countries recognize the rise in patients with beta-thalassemia and have increased resources to meet the growing demand. While in Northern and Western Europe, health professionals and policymakers acknowledge this trend, they lack reliable data on the frequency and patterns of the disease.
Beta-thalassemia treatment requires significant expertise and resources, including safe blood donations. The COVID pandemic has had a significant impact on the blood supply throughout the world, creating a drop in the number of blood donations in most EU countries and particular challenges in developing and low-income countries with limited resources and high concentrations of patients with the disease.
According to Professor Ali Taher of American University of Beirut, addressing the impact of the pandemic on the beta thalassemia patient community will require ongoing effort. Currently, the only available cure for beta-thalassemia is a stem cell transplant, but many patients may not be eligible. Fewer than 10 percent of patients eligible for a stem cell transplant actually receive one, often due to high costs or a lack of a donor.
In recent years, however, advances in the treatment landscape have provided much needed options to address anemia resulting from beta-thalassemia and provide patients with the possibility of becoming less dependent on red blood cell transfusions.
Modell B, Darlison M. Global epidemiology of haemoglobin disorders and derived service indicators. WHO Bull. Accessed November 28, Needs T, Lynch DT. Beta thalassemia. October 2, Accessed November 21,
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