Medication Summary
No specific medications are currently available for the treatment of thalassemia intermedia that have been proven in large-scale trials. Most patients with severe disease are prone to developing megaloblastic anemia due to folate deficiency, which primarily results from the extreme demand of the very active bone marrow for folic acid, and a low daily dose of folate is advisable. Agents such as hydroxyurea have been found to induce erythropoiesis in a subset of patients and to raise Hb levels. [19] Thalidomide has also been found to be effective in some patients in raising hemoglobin, presumably by inducing fetal Hb production, but large-scale studies are lacking. [20]
Many patients with thalassemia intermedia may ultimately require regular blood transfusions, usually about every 3-5 weeks. Similar to patients with thalassemia major, patients with thalassemia intermedia who receive regular transfusions are usually premedicated with an antipyretic, such as acetaminophen, and an antihistamine, such as diphenhydramine, 30 minutes before transfusion to prevent both febrile and allergic reactions.
Patients with iron overload should be treated with chelation therapy. The drugs of choice in current practice are the oral agents deferasirox and deferiprone. Alternatively, deferoxamine may be administered subcutaneously by infusion pump overnight 5-7 times per week while the patient sleeps. Low-dose vitamin C with each infusion of deferoxamine is beneficial in enhancing iron chelation. Combination therapy with more than one agent has proved to be effective in certain situations.
Patients with iron overload who develop fever of unknown origin may have Yersinia enterocolitica infection. Treatment with gentamicin and oral trimethoprim-sulfamethoxazole should be initiated if no other cause for the fever is identified.
Other agents that may be of value in patients with thalassemia intermedia include vitamin E, which may prevent some of the toxic effects of the free radicals and other iron-related toxicity. Penicillin or one of its derivatives should be prophylactically administered for patients who have undergone a splenectomy. A daily low dose of aspirin is advised as prophylactic treatment to prevent thrombotic events in patients with thalassemia intermedia who have undergone a splenectomy.
Analgesics, Other
Class Summary
Analgesic antipyretic agents can help prevent febrile reactions in patients who are frequently transfused and who thus may develop sensitization to blood products.
Acetaminophen (FeverAll, Tylenol, Mapap, Acephen)
Acetaminophen has an antipyretic effect through action on the hypothalamic heat-regulating center. Although this drug is equal to aspirin in action, acetaminophen is preferred, because it has fewer adverse effects.
Antihistamines, 1st Generation
Class Summary
Antihistamine agents prevent or ameliorate allergic reactions that are associated with the transfusion of blood products.
Diphenhydramine hydrochloride (Benadryl, Diphenhist, Aler-Cap)
Diphenhydramine elicits anticholinergic and sedative effects.
Chelators
Class Summary
Chelating agents are an integral part of successful treatment of thalassemia. They remove excess iron deposits that are the main cause of long-term morbidity and mortality in this condition.
Deferoxamine mesylate (Desferal)
Deferoxamine chelates iron from ferritin and hemosiderin but not from transferrin, cytochrome, or hemoglobin (Hb). This agent helps prevent damage to the liver and bone marrow from iron deposition.
Deferasirox (Exjade)
Deferasirox is available as a tablet for oral suspension. It is an oral iron-chelating agent that reduces liver iron concentration and serum ferritin levels. Deferasirox binds iron with high affinity in a 2:1 ratio. It is approved for treatment of treat chronic iron overload due to multiple blood transfusions and non–transfusion-dependent thalassemia.
Antibiotics, Other
Class Summary
Antimicrobial agents are known to be effective against organisms that may cause infection in patients with iron overload who are also receiving deferoxamine therapy. Y enterocolitica infections are rare in healthy patients, because the organism requires siderophores, which are present in patients with thalassemia but not in healthy patients. The appropriate therapy is a combination of trimethoprim-sulfamethoxazole and gentamicin. Patients who require splenectomy must receive prophylactic antibiotics to prevent fulminating sepsis, especially patients younger than 5 years.
Trimethoprim-sulfamethoxazole (Bactrim, Bactrim DS, Septra DS)
By blocking tetrahydrofolic acid, trimethoprim-sulfamethoxazole selectively inhibits synthesis of nucleic acids and proteins by bacteria.
Penicillin V
Penicillin V is the drug of choice (DOC) for prophylaxis in patients with thalassemia who have undergone a splenectomy (erythromycin is used in patients allergic to penicillin). This agent is active against most microorganisms that are considered to be major pathogens in splenectomized patients (ie, streptococcal, pneumococcal, and some staphylococcal microorganisms) but not penicillinase-producing species. Prophylaxis with penicillin V is provided for more than 3 years after splenectomy.
Erythromycin (E.E.S., Ery-Tab, Erythrocin)
Erythromycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. It is used for the treatment of staphylococcal and streptococcal infections.
Vitamins, Water-Soluble
Class Summary
Vitamins are compounds that are present in small amounts in food, and they are essential for normal metabolism, cell function, and healthy tissues.
Ascorbic acid (Cecon, Cevalin, Vita-C)
Vitamin C has been shown to enhance the function of deferoxamine by keeping iron in a form that can be chelated. When administered with deferoxamine, vitamin C allows more iron to be removed.
Folic acid (Folvite)
Folic acid is required for DNA synthesis; therefore, patients with all conditions associated with rapid cellular turnover, such as hyperactive marrow in thalassemia, have greatly increased demand. Because use of folic acid in hemolytic anemias is extreme, deficiency states are fairly common in most of these patients. Patients who do not receive folic acid supplementation may develop megaloblastic anemia, thereby increasing the severity of the original disease process.
Vitamins, Fat-Soluble
Class Summary
The antioxidant effects of vitamin E have been shown to help in decreasing iron-mediated toxic effects on cells by preventing or decreasing membrane-lipid peroxidation.
Vitamin E (Key-E, Aqua Gem-E, E-Gems, Aquasol E)
The mechanism of action (MOA) of vitamin E has been known for many years. In newborn or premature infants, in particular, vitamin E deficiency has resulted in peculiar red blood cell (RBC) morphology, leading to hemolysis; these changes are reversed by vitamin E. Peroxidation of membrane lipids by various oxidants, including iron-mediated oxygen radicals, is the main cause of this hemolysis and can be prevented by antioxidants such as vitamin E.
Corticosteroids
Class Summary
Corticosteroid agents can help prevent local and systemic reactions to exogenous agents.
Hydrocortisone (Solu-Cortef, Cortef)
Hydrocortisone is an anti-inflammatory adrenocortical steroid. This agent helps prevent local reaction to subcutaneous (SC) perfusion of deferoxamine. Both sodium succinate (Solu-Cortef) and sodium phosphate (Cortef) forms are used for intravenous (IV) infusions, but sodium acetate form (Hydrocortone) is not.
Vaccines, Inactivated, Bacterial
Class Summary
Patients who have undergone a splenectomy are prone to developing infections with any of 3 common encapsulated organisms (ie, Pneumococcus species [spp], H influenzae, and Meningococcus spp). Patients who are to undergo splenectomy now receive immunizations against these organisms 1-2 weeks before the procedure. This practice allows the spleen to participate in production of antibodies before being removed.
Pneumococcal vaccine polyvalent (Pneumovax-23)
The older polyvalent/polysaccharide pneumococcal vaccine contains the 23 most prevalent serotypes responsible for about 70% of all invasive infectious diseases, but it cannot be administered to children younger than 2 y. A new generation of this vaccine, called conjugate vaccine, is now available; it has only 7 serotypes, but it can be administered to infants as young as 2 months. This is a very important achievement, because splenectomized infants are more prone to develop pneumococcal infections than any other group of patients. The conjugate form is administered in a series of 2-3 doses at ages 2, 4, and 6 months.
Haemophilus influenza type b vaccine (ActHIB, PedvaxHIB)
Haemophilus influenzae type b vaccine is recommended 2 weeks before splenectomy. Patients who have already received their primary vaccination early in life and also received a booster at 12 months or later are usually protected, even though they may benefit from an additional dose before the procedure. The conjugate form is administered in a series of 2-3 doses at ages 2, 4, and 6 months.
Meningococcal vaccine (Menomune A/C/Y/W-135)
Meningococcal vaccine is similar to polyvalent pneumococcal vaccine. This vaccine is used in children older than 2 years who are at risk (eg, complement deficiency, asplenia). Meningococcal vaccine contains a serogroup specific against groups A, C, Y, and W-135 N meningitides.
Pneumococcal 7-valent conjugate vaccine (Prevnar)
Pneumococcal 7-valent conjugate vaccine is a sterile solution of saccharides of capsular antigens of Streptococcus pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F individually conjugated to diphtheria CRM197 protein. These 7 serotypes have been responsible for over 80% of invasive pneumococcal disease in children younger than 6 years in the United States; they also accounted for 74% of penicillin-nonsusceptible S pneumoniae (PNSP) and 100% of pneumococci with high-level penicillin resistance. The customary age for the first dose of pneumococcal 7-valent conjugate vaccine is 2 months, but it can be administered to infants as young as 6 weeks.
Erythropoiesis
Class Summary
Hydroxyurea was found to induce erythropoiesis and raise hemoglobin (Hb) levels. [19] Thalidomide has been found effective in raising hemoglobin in case reports and small case series but large-scale studies are lacking [20]
Hydroxyurea (Hydrea, Droxia)
It inhibits deoxynucleotide synthesis. S-phase specific non-DNA hypomethylation chemotherapeutic agent. Mechanism of action for thalassemia is unknown but has shown HbF-inducing activity.
Thalidomide (Thalomid)
Mechanism of action for thalassemia is unknown but has shown HbF-inducing activity.
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Peripheral blood film in thalassemia intermedia.
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Basophilic stippling in thalassemia intermedia.
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Nucleated red blood cell in thalassemia intermedia.
