Medication Summary
Medications for the treatment of beta thalassemia are primarily intended to minimize the complications associated with chronic transfusions and the disease process. Chelation therapy is essential to mitigate the toxic effects of transfusional iron overload, and monitoring includes assessment of iron burden, as well as any side effects from treatment. [28, 16, 7]
Deferoxamine, deferasirox, and deferiprone are the three chelators licensed for US use. [7] Adherence to chelation therapy is key to successful long-term outcomes. Complications of chelator use include the following:
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Deferoxamine, which is administered as a continuous subcutaneous infusion, commonly produces local reactions, including erythema and induration [7]
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Deferasirox is prone to causing gastrointestinal (GI) upset, which worsens adherence; there have been reports of renal and hepatic dysfunction and cytopenias, so a CBC, a creatinine assessment, a urinalysis, and liver function tests should be conducted monthly
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Deferiprone is associated with reversible neutropenia occurring at a rate of 0.2/100 patient years, and regular blood counts are advised; liver inflammation sometimes occurs, and serum alanine aminotransferase (ALT) should be monitored at least every 3 months
Some medications, such as hydroxyurea and thalidomide, have the potential to increase the Hb level in a subset of patients. In 2019, the novel agent luspatercept-aamt, which minimizes red cell destruction by decreasing α-globin production, was approved by the FDA for the treatment of beta thalassemia. [46]
The one-time gene therapy betibeglogene autotemcel has been approved in Europe and the United States.
Antipyretics, analgesics
Class Summary
Administration before blood transfusion prevents or decreases febrile reactions.
Acetaminophen (Tylenol, Tempra, Panadol)
Antipyretic effect through action on hypothalamic heat-regulating center. Action equal to that of aspirin but preferred because does not have adverse effects of aspirin.
Antihistamines
Class Summary
Administration prior to blood transfusion may decrease or prevent allergic reactions.
Diphenhydramine hydrochloride (Benadryl)
Antihistamine with anticholinergic and sedative effects.
Chelating agents
Class Summary
These agents are used to chelate excessive iron from the body in patients with iron overload.
Deferoxamine mesylate (Desferal)
Chelates iron from ferritin or hemosiderin but not from transferrin, cytochrome, or Hb.
Deferasirox (Exjade)
Deferasirox comes in tablet form for oral suspension. It is an oral iron chelation agent that reduces liver iron concentration and serum ferritin levels. Deferasirox binds to iron with a high affinity, in a 2:1 ratio. It is approved to treat chronic iron overload due to multiple blood transfusions and nontransfusion-dependent thalassemia.
Deferiprone (Ferriprox)
Deferiprone is an iron chelator indicated for adults and children aged 3 years or older, in whom transfusional iron overload has resulted from a thalassemia syndrome or from sickle cell disease or other anemia. It is available in tablet form or as an oral solution.
Corticosteroids
Class Summary
Some patients may develop local reaction at the site of DFO injection. Hydrocortisone in the DFO solution may help to reduce the reaction.
Hydrocortisone (Solu-Cortef, Cortef, Hydrocortone)
Anti-inflammatory action. Both Na succinate (Solu-Cortef) and Na phosphate (Cortef) forms used for IV infusion, but not Na acetate form (Hydrocortone).
Antibacterial combinations
Class Summary
Yersinia enterocolitica infections are more common in iron-overloaded patients with transfusion-dependent thalassemia. Appropriate therapy is a combination of trimethoprim-sulfamethoxazole and gentamicin. Patients who require splenectomy need to receive prophylactic penicillin to reduce the risk of fulminant sepsis.
Trimethoprim-sulfamethoxazole (TMP/SMX, Bactrim, Septra)
In combination with gentamicin, DOC for infections by Y enterocolitica.
Gentamicin (Garamycin)
Aminoglycoside known to be effective against gram-negative microorganisms. Dosing regimens are numerous; adjust dose based on CrCl and changes in volume of distribution.
Penicillin V (Pen-Vee, Veetids, V-Cillin K)
DOC for postsplenectomy prophylaxis; erythromycin used in patients allergic to penicillin. Active against most microorganisms considered to be major offenders in splenectomized patients, namely, streptococcal, pneumococcal, and some staphylococcal microorganisms, but not penicillinase-producing species.
Vitamins
Class Summary
Several vitamins are required, as either supplements or enhancers of the chelating agent.
Serum level of vitamin C is low in patients with thalassemia major, likely due to increased consumption in the face of iron overload.
Ascorbic acid (Vitamin C, Cebid, Vita-C, Ce-Vi-Sol, Cecon, Dull-C)
Delays conversion of transferrin to hemosiderin, thus making iron more accessible to chelation.
Alpha-tocopherol (Vitamin E, Aquasol E, Vita-Plus E Softgels, Vitec, E-Vitamin)
An antioxidant. Prevents iron-mediated toxicity caused by peroxidation of cell membrane lipids, reducing extent of accompanying hemolysis. Protects polyunsaturated fatty acids in membranes from attack by free radicals and protects RBCs against hemolysis. Demonstrated to be deficient in patients with iron overload receiving chelation therapy.
Folic acid (Folvite)
Required for DNA synthesis; therefore in great demand in these patients because of increased cellular turnover. Deficient in most patients with chronic hemolysis.
Vaccines
Class Summary
Splenectomized patients are usually prone to developing infections with the encapsulated organisms such as pneumococci, Haemophilus influenzae, and meningococcal organisms. For this reason, such patients now are immunized against these organisms 1-2 wk prior to the procedure to prevent infections.
Pneumococcal vaccine polyvalent (Pneumovax)
Polyvalent polysaccharide vaccine (PS23) contains 23 serotypes that cause 70% of invasive infections. This vaccine should not be given to children < 2 y. In rare cases in which splenectomy is required in children < 2 y and no previous vaccination has been given, conjugate type (PCV7), which contains only 7 serotypes, is required.
Haemophilus influenza type b vaccine (ActHIB, HibTITER, PedvaxHIB)
Used for routine immunization of children against invasive diseases caused by H influenzae type b. Decreases nasopharyngeal colonization. The CDC's Advisory Committee on Immunization Practices (ACIP) recommends that all children receive one of the conjugate vaccines licensed for infant use beginning routinely at age 2 mo.
Conjugate form usually given in series of 3 doses at ages 2, 4, and 6 mo. Patients who have already received primary vaccine and booster dose at age 12 mo or older are usually protected and do not require further vaccination prior to splenectomy.
Meningococcal A C Y and W-135 polysaccharide vaccine combined (Menomune A/C/Y/W-135)
Used only in children >2 y. Serogroup specific against groups A, C, Y, and W-135 Neisseria meningitidis.
Pneumococcal vaccine 13-valent (Prevnar 13)
Sterile solution of saccharides of capsular antigens of S pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F individually conjugated to diphtheria CRM197 protein. Primary series consists of 4 doses at ages 2, 4, 6, and 12-15 months. Additionally, supplemental dose indicated for individuals at high risk.
Antineoplastic agent
Class Summary
Some patients may respond to hydroxyurea and subsequently decrease or eliminate transfusion requirements. Patients with homozygous or heterozygous XmnI polymorphism were found to respond favorably in one study. [47] Improvement of pulmonary hypertension following hydroxyurea has also been observed. [48]
Hydroxyurea (Droxia, Hydrea)
Inhibitor of deoxynucleotide synthesis.
Growth Hormone
Class Summary
Excessive chelation with deferoxamine may cause growth retardation. Growth hormone may be effective in increasing growth rate in all thalassemic patient particularly the ones with growth hormone deficiency. [49]
Somatropin (Saizen, Genotropin, Humatrope, Norditropin, Tev-Tropin)
Human growth hormone produced by recombinant DNA technology (mouse C127 cell line). Elicits anabolic and anticatabolic influence on various cells including: myocytes, hepatocytes, adipocytes, lymphocytes, and hematopoietic cells. Exerts activity on specific cell receptors including insulinlike growth factor-1 (IGF-1).
Antiplatelet Agents, Hematologic
Class Summary
Antiplatelet agents are used for reduction of platelet adhesiveness in thrombotic disease and as anti-inflammatory agents for immune-mediated or noninfectious inflammatory conditions.
Aspirin (Acetylsalicylic acid, ASA, Bayer Advanced Aspirin)
Aspirin inhibits prostaglandin synthesis, preventing the formation of platelet-aggregating thromboxane A2. It may be used in a low dose to inhibit platelet aggregation and improve complications of venous stases and thrombosis.
Erythroid Maturation Agents
Class Summary
In November 2019, the first erythroid maturation agent was approved for anemia in adults with beta thalassemia who require regular red blood cell (RBC) transfusions.
Luspatercept (Luspatercept-aamt, Reblozyl)
Suppresses growth differentiation factor 11 (GDF11), an activin receptor IIA (ActRIIA) ligand that is increased in erythroblasts in beta thalassemia. Oxidative stress is consequently reduced, as is the amount of α-globin membrane precipitate, thus increasing terminal erythroid differentiation and decreasing ineffective erythropoiesis.
Gene Therapy, Hematologics
Class Summary
One-time IV infusion that transduces autologous CD34+ cells via a lentiviral vector, thus providing a patient’s hematopoietic stem cells (HSCs) with functional copies of a modified β-globin gene. Adding the functional gene addresses the underlying genetic cause of beta thalassemia.
Betibeglogene autotemcel (Zynteglo)
Indicated for beta thalassemia in patients in whom regular red blood cell transfusions have been required. After IV infusion, engraftment of transduced CD34+ HSCs in bone marrow occurs, with these HSCs differentiating to produce RBCs carrying biologically active betaA-T87Q-globin (a modified β-globin protein). When this protein combines with α-globin, functional hemoglobin containing betaA-T87Q-globin (HbA-T87Q) is produced.
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Alpha chain genes in duplication on chromosome 16 pairing with non-alpha chains to produce various normal hemoglobins.
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Alpha and beta globin genes (chromosomes 16 and 11, respectively).
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Various mutations in the beta gene that result in beta thalassemia.
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Supra vital stain in hemoglobin H disease that reveals Heinz bodies (golf ball appearance).
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Peripheral blood film in Cooley anemia.
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Peripheral blood film in thalassemia minor.
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Peripheral blood film in hemoglobin H disease in a newborn.
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Peripheral blood in iron deficiency anemia.
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The classic "hair on end" appearance on plain skull radiographs of a patient with Cooley anemia.
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Excessive iron in a bone marrow preparation.
