eMedicine Specialties > Pediatrics: General Medicine > Hematology
Thalassemia Intermedia: Treatment & Medication
Updated: Sep 29, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
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Treatment
Medical Care
The treatment of most cases of thalassemia intermedia involves close monitoring and observation.
- Patients with satisfactory hemoglobin (Hb) levels are frequently monitored.
- These patients usually require blood transfusions only on certain occasions such as the presence of intercurrent infections, hypersplenism, or other illnesses.
- If patients can no longer maintain an Hb level of more than 6 g/dL, they are either started on a regimen of regular blood transfusions or a different option, such as splenectomy, should be tried. Patients with evidence of hypersplenism have a good chance to have their need for blood transfusion reduced or totally eliminated; this might last for months or years. Others may try to administer one of the drugs that may induce stress erythropoiesis and raise Hb levels. Hydroxyurea has been frequently used for this purpose. In separate studies on a large number of patients, a response rate exceeding 75% was reported after long-term therapy.19 However, this high rate of response was not confirmed by other studies until a study on a small number of patients with β thalassemia major and intermedia treated with hydroxyurea demonstrated a response rate of more than 82%.20
- The initial regimen includes transfusion of 10-15 mL of packed red blood cells (PRBC) every 4-5 weeks to keep the Hb level over 10 g/dL.
- Blood transfusions should be leukocyte poor to avoid sensitization because such patients have the potential of becoming transfusion dependent in the future.
- Patients should be checked and typed for minor blood groups to avoid further difficulties in providing appropriate blood for them in the future.
- Identification of a small group of dedicated donors minimizes the risk of viral exposure and alloimmunization.
- Iron status must be carefully monitored, and patients with iron overload should be treated with an aggressive chelation regimen as soon as indicated.
- A popular chelation regimen includes administration of deferoxamine 5 days per week as a subcutaneous infusion over 8-12 hours. This regimen revolutionized the treatment of β thalassemia major in patients regularly receiving PRBC transfusions and resulted in longer survival and near-normal quality of life. An oral iron chelator, deferasirox (Exjade), has been in use in the United States for some time now. This agent has a long half-life and, for this reason, is orally administered once daily. Several studies have confirmed the long-term efficacy and safety of this agent. It is now much more popular and, due to the ease and convenience of administration and better compliance, is probably replacing deferoxamine.21
- A similar dose is often administered at the time of blood transfusions to help bind the transfused iron (from hemolyzed RBCs).
- Nutritional deficiencies should be addressed and treated.
- A folic acid supplement should be administered.
- Vitamin C supplementation has been effective in enhancing the efficiency of chelating iron from tissues.
- Patients who have undergone a splenectomy should be placed on prophylactic antibiotics and be treated empirically for any signs of infection or fever while awaiting the results of blood cultures.
- Appropriate vaccinations, including the polyvalent polysaccharide pneumococcal, the Haemophilus influenzae type b, and the quadrivalent meningococcal vaccines, should be administered to patients 1-2 weeks before splenectomy.
- Patients with severe β thalassemia intermedia are prone to infection with Yersinia enterocolitica, similar to individuals with the severe forms of thalassemia major. For this reason, patients who develop fever without clear cause should receive appropriate treatment even if culture results are negative.
- Young children should have their growth and development closely monitored; any deviation from normal should alert the physician to further investigate the need for blood transfusions.
- Failure to thrive, exercise intolerance, bone deformities and fractures are all potential complications; the health care provider should always look for ways to prevent these complications or at least identify and treat them early with regular blood transfusions, which are frequently effective in reversing or preventing their progress.
- In patients with severe thalassemia intermedia who require aggressive therapy to sustain life, bone marrow transplant, similar to that performed in patients with thalassemia major, is a reasonable alternative to transfusion and chelation if a matched sibling donor is available.
- Many studies have shown that patients with thalassemia intermedia who are not on regular blood transfusion because of their milder symptoms nevertheless develop major complications related to their chronic anemia and ineffective erythropoiesis (IE). Considering the cost-benefit balance of regular treatment in patients with thalassemia major, most patients with thalassemia intermedia would apparently benefit from similar therapy to prevent the complications, rather than waiting to deal with such complications when they occur.
Surgical Care
- Splenectomy is frequently recommended for patients who are no longer able to maintain an adequate Hb level. It is usually performed to restore the Hb steady state in patients who are not receiving blood transfusions and frequently succeeds in averting the need for regular transfusions.
- Observations and case reports have shown that splenectomy in such patients may cause serious venous thrombotic events, ranging from deep vein thrombosis to pulmonary thrombotic lesions complicated by pulmonary hypertension.22,23,7,24 Several reports of serious thrombotic events such as transient ischemic attacks associated with hemiparesis and intracranial manifestations of Moyamoya syndrome were reported postsplenectomy in patients with thalassemia intermedia.24 For this reason, one should delay or reconsider such a procedure whenever possible. This is supported by the fact that many children who underwent splenectomy to avoid becoming transfusion dependent experienced only a transient effect, and most later required regular transfusions.
- Placement of a central vascular access catheter in patients with severe disease is very helpful for blood transfusions, and laboratory work, especially when accessing a patient's peripheral veins becomes very difficult.
- In the rare patient with large tumorlike masses that compress vital organs, surgical resection rather than radiation therapy is usually preferred.
- Liver biopsy is indicated in the patient receiving chelation therapy for hemosiderosis to evaluate the degree of liver involvement and iron overload.
Consultations
- Patients in whom thalassemia is suspected should be seen and evaluated by a hematologist.
- Consultation with a cardiologist is indicated to evaluate cardiac function and monitor potential complications due to the anemia, transfusion, or iron overload.
- Consultation with an endocrinologist is also indicated for evaluation of possible involvement of various endocrine glands, which could result in diabetes mellitus, thyroid disorder, or growth retardation.
- Patients should be seen by a gastroenterologist for diagnosis and management of liver complications.
Diet
- A well-balanced diet with adequate folic acid supply is a necessity. Foods with high iron content should be avoided, particularly meat because heme iron is especially well absorbed. Vitamin C assists absorption of dietary iron; patients should avoid co-ingesting vitamin C and iron-rich foods.
- Alternatively, drinking tea with iron-rich foods helps chelate some of the iron before it is absorbed in the bowels.
Activity
- Many patients with thalassemia intermedia should be able to tolerate most daily activities. However, once the anemia worsens, exercise intolerance develops and may represent a warning sign indicating the need for initiation of blood transfusions.
- Massive splenomegaly has been observed in severe cases and is a cause for limiting the patient's activity for fear of injury to the abdomen causing rupture of the spleen.
- Regular transfusions decrease the size of the spleen in most instances, allowing splenectomy to be avoided whenever possible.
Medication
No specific medications are available for the treatment of thalassemia intermedia. Most patients with severe disease are prone to developing megaloblastic anemia due to folate deficiency for several reasons, including poor absorption, low dietary intake, and, most importantly, the extreme demand of the very active bone marrow for folic acid. For this reason, most patients benefit from a low dose of folate.
Many patients with thalassemia intermedia 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 (orally or parenterally). The drugs of choice at the present time are the oral agent deferasirox and deferoxamine administered subcutaneously by infusion pump 5 times per week. It can be administered 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 Y enterocolitica infection. Treatment with gentamicin and oral trimethoprim-sulfamethoxazole should be initiated if no other cause for the fever is identified.
Hepatitis C virus (HCV) infection is the most common cause of hepatitis in patients with thalassemia. Because of the high risk of liver failure or even hepatocellular carcinoma in a liver already damaged by iron toxicity and frequent blood transfusions, HCV infection should be aggressively treated in these patients. Interferon alfa therapy has been effective in many children with HCV infection.
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. Some have also recommended a daily low dose of aspirin as prophylactic treatment in patients with thalassemia intermedia who underwent a splenectomy to prevent thrombotic events.
Antipyretics, analgesic
These agents can help prevent febrile reactions in patients who are frequently transfused and thus may develop sensitization to blood products.
Acetaminophen (Feverall, Tylenol, Tempra)
Antipyretic effect through action on hypothalamic heat-regulating center. Although equal to aspirin in action, preferred because it has fewer adverse effects.
Adult
325-650 mg PO 30 min before transfusion
Pediatric
10-15 mg/kg/dose PO 30 min before transfusion
Rifampin can reduce analgesic effects of acetaminophen; coadministration with barbiturates, carbamazepine, hydantoins, and isoniazid may increase hepatotoxicity
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Hepatotoxicity possible in people with chronic alcoholism following various dose levels; severe or recurrent pain or high or continued fever may indicate a serious illness; APAP is contained in many OTC products, and combined use with these products may result in cumulative APAP doses exceeding recommended maximum dose
Antihistamines
These agents prevent or ameliorate allergic reactions associated with transfusion of blood products.
Diphenhydramine hydrochloride (Benadryl, Benylin)
Elicits anticholinergic and sedative effects.
Adult
25-50 mg PO q6-8h prn; not to exceed 400 mg/d
10-50 mg IV/IM q6-8h prn; not to exceed 400 mg/d
Pediatric
Neonates and premature infants: Do not administer
Infants and children: 1 mg/kg/dose PO/IV q6h or 5 mg/kg/d PO/IV divided q6h
Potentiates effect of CNS depressants; because of alcohol content, do not administer syr dosage form to patient taking medications that can cause disulfiramlike reactions
Documented hypersensitivity; MAOIs
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May exacerbate angle closure glaucoma, hyperthyroidism, peptic ulcer, and urinary tract obstruction
Chelating agents
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)
Chelates iron from ferritin and hemosiderin but not from transferrin, cytochrome, or Hb. Helps prevent damage to liver and bone marrow from iron deposition.
Adult
1000 mg IV may be administered at a rate not to exceed 15 mg/kg/h; follow by a dose of 500 mg q4h for 2 doses; may administer additional IV infusion slowly over 24 h; not to exceed 6000 mg/d
Pediatric
20-40 mg/kg/d SC by infusion pump over 8-12 h 5 d/wk
With blood transfusions: 1-2 g IV slow infusion; not to exceed infusion rate of 15 mg/kg/h
Can cause loss of consciousness when administered with prochlorperazine
Documented hypersensitivity; patients that do not have acute iron poisoning; severe renal disease and anuria (dose reduction after the loading dose should be considered in these circumstances)
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Tachycardia, hypotension, and shock may occur in patients receiving long-term therapy and could add to the cardiovascular collapse due to iron toxicity; GI adverse effects of the drug include abdominal discomfort, nausea, vomiting, and diarrhea, which may add to the symptoms of acute iron toxicity; flushing and fever are reported; increased susceptibility to Y enterocolitica infection
Deferasirox (Exjade)
Tab for oral susp. Oral iron chelation agent demonstrated to reduce liver iron concentration in adults and children who receive repeated RBC transfusions. Binds iron with high affinity in a 2:1 ratio. Approved to treat chronic iron overload due to multiple blood transfusions. Treatment initiation recommended with evidence of chronic iron overload (ie, transfusion of about 100 mL/kg packed RBCs [about 20 U for 40-kg person] and serum ferritin level consistently >1000 mcg/L).
Adult
Initial: 20 mg/kg/d PO on empty stomach 30 min ac; as initial dose calculate dose to nearest whole tab
Maintenance: Adjust dose by 5- to 10-mg/kg/d increments q3-6mo according to serum ferritin level trends; not to exceed 30 mg/kg/d
Note: Dissolve tab completely in water, orange juice, or apple juice, then immediately drink susp; resuspend any remaining residue in small volume of liquid and swallow
Pediatric
<2 years: Not established
>2 years: Administer as in adults
Data limited; do not take with aluminum-containing antacids
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Common adverse effects include diarrhea, nausea, abdominal pain, headache, pyrexia, cough, and rash; may increase serum creatinine and hepatic enzyme levels; decrease dose with persistent elevation of serum creatinine level; may cause auditory and visual disturbances; slight decreases in serum copper and zinc levels may occur; dissolve tab completely in water, orange juice, or apple juice and drink resulting susp immediately (do not swallow tab whole, do not chew or crush); measure serum ferritin levels monthly and adjust dose every 3-6 mo based on serum ferritin trends
Antimicrobial agents
These 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, Septra, Cotrim)
By blocking tetrahydrofolic acid, selectively inhibits synthesis of nucleic acids and proteins by bacteria.
Adult
160 mg (trimethoprim)/800 mg (sulfamethoxazole) PO q12h (ie, one double-strength [DS] tab PO q12h)
Pediatric
<2 months: Do not administer
>2 months: 8-10 mg/kg/d (based on trimethoprim component) PO/IV divided q12h
May increase PT when used with warfarin (perform coagulation tests and adjust dose accordingly); coadministration with dapsone may increase blood levels of both drugs; coadministration of diuretics increases incidence of thrombocytopenia purpura in elderly patients; phenytoin levels may increase with coadministration; may potentiate effects of methotrexate in bone marrow depression; hypoglycemic response to sulfonylureas may increase with coadministration; may increase levels of zidovudine
Documented hypersensitivity; megaloblastic anemia due to folate deficiency; age <2 mo
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Do not use near term in pregnancy because of risk of kernicterus; discontinue at first appearance of skin rash or sign of adverse reaction; obtain CBC counts frequently; discontinue therapy if significant hematologic changes occur; goiter, diuresis, and hypoglycemia may occur with sulfonamides; prolonged IV infusions or high doses may cause bone marrow depression (if signs occur, administer 5-15 mg/d leucovorin); caution in folate deficiency (eg, people with long-term alcoholism, elderly people, those receiving anticonvulsant therapy, those with malabsorption syndrome); hemolysis may occur in individuals with G-6-PD deficiency; patients with AIDS may not tolerate or respond to therapy; caution in renal or hepatic impairment (perform urinalyses and renal function tests during therapy); administer fluids to prevent crystalluria and stone formation
Gentamicin
An aminoglycoside. Effective against gram-negative aerobic microorganisms.
Adult
1-1.5 mg/kg IV q8h with normal renal function
Pediatric
6-7.5 mg/kg/d IV divided q8h
Coadministration with other aminoglycosides, cephalosporins, penicillins, and amphotericin B may increase nephrotoxicity; aminoglycosides enhance effects of neuromuscular blocking agents, thus prolonged respiratory depression may occur; coadministration with loop diuretics may increase auditory toxicity of aminoglycosides; possible irreversible hearing loss of varying degrees may occur (monitor regularly)
Documented hypersensitivity; non–dialysis-dependent renal insufficiency
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Narrow therapeutic index (not intended for long-term therapy); caution in renal failure (patient not on dialysis), myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission; adjust dose in renal impairment
Penicillin V (Veetids)
DOC for prophylaxis in patients with thalassemia who have undergone a splenectomy (erythromycin used in patients allergic to penicillin); active against most microorganisms considered to be major pathogens in splenectomized patients (ie, streptococcal, pneumococcal, and some staphylococcal microorganisms) but not penicillinase-producing species. Prophylaxis provided for >3 y after splenectomy.
Adult
250-500 mg PO bid
Pediatric
<5 years: 125 mg/dose PO bid
>5 years: 250 mg/dose PO bid
Streptococcal infections: Administer above doses for >10 d
Prophylaxis: Treat for >3 y after splenectomy
Probenecid may increase effectiveness by decreasing clearance; tetracyclines are bacteriostatic, causing a decrease in the effectiveness of penicillins when administered concurrently
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Patients with asthma may have hypersensitivity; PO route usually not adequate for treatment of severe infections; treat for minimum of 10 d for streptococcal infections
Vitamins
These agents are compounds that are present in small amounts in food and 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, allows more iron to be removed.
Adult
100-200 mg/d PO during deferoxamine therapy
Pediatric
3 mg/kg/d PO with SC deferoxamine infusion
Decreases effects of warfarin and fluphenazine; increases aspirin levels
Documented hypersensitivity
Pregnancy
A - Fetal risk not revealed in controlled studies in humans
Precautions
Use in patients with severe iron overload may induce a short-term deterioration with acute cardiac toxicity
Folic acid (Folvite)
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, increasing the severity of the original disease process.
Adult
1 mg PO qd
Pediatric
Administer as in adults
Increase in seizure frequency and a decrease in subtherapeutic levels of phenytoin reported when used concurrently
Documented hypersensitivity; pernicious anemia; aplastic anemia
Pregnancy
A - Fetal risk not revealed in controlled studies in humans
Precautions
Pregnancy category C if dose exceeds RDA; benzyl alcohol may be contained in some products as a preservative (associated with a fatal gasping syndrome in premature infants); resistance to treatment may occur in patients with alcoholism and deficiencies of other vitamins
Antioxidants
Vitamin E has been shown to help in decreasing iron-mediated toxic effects on cells by preventing or decreasing membrane-lipid peroxidation.
Vitamin E (Vita-Plus E Softgels, Vitec, Aquasol E)
MOA has been known for many years. In newborn or premature infants, in particular, deficiency has resulted in peculiar red blood cell 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.
Adult
50-2000 IU/d PO
Pediatric
1 IU/kg/d PO
Mineral oil decreases absorption of vitamin E; vitamin E delays absorption of iron and increases effects of anticoagulants
Documented hypersensitivity
Pregnancy
A - Fetal risk not revealed in controlled studies in humans
Precautions
Pregnancy category C if dose exceeds RDA; vitamin E may induce vitamin K deficiency; necrotizing enterocolitis may occur when large doses of vitamin E are administered
Corticosteroids
These agents can help prevent local and systemic reactions to exogenous agents.
Hydrocortisone (Solu-Cortef, Cortef)
An anti-inflammatory adrenocortical steroid. Helps prevent local reaction to SC perfusion of deferoxamine. Both sodium succinate (Solu-Cortef) and sodium phosphate (Cortef) forms are used for IV infusions, but sodium acetate form (Hydrocortone) is not.
Adult
Pediatric
Newborns: Do not administer
Infants and children: 5-10 mg added to deferoxamine solution before infusion
Corticosteroid clearance may decrease with estrogens; may increase digitalis toxicity secondary to hypokalemia
Documented hypersensitivity; systemic fungal infection; tuberculosis; peptic ulcer; newborn infant (because of benzyl alcohol content)
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Many adverse effects are known, but minimal doses used in this setting reduce this concern; however, because deferoxamine therapy is long term and must be administered almost daily, serious consideration is required for any condition that might be a contraindication; abrupt withdrawal may cause acute adrenal insufficiency; caution in hyperthyroidism, liver cirrhosis, ulcerative colitis, hypertension, and osteoporosis
Vaccines
Patients who have undergone a splenectomy are prone to developing infections with any of 3 common encapsulated organisms (ie, Pneumococcus species, H influenzae, and Meningococcus species). 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/PS23 (Pneumovax-23, Pnu-Imune 23)
The older polyvalent/polysaccharide vaccine contains the 23 most prevalent serotypes responsible for about 70% of all invasive infectious diseases, but it cannot be administered to children <2 y. A new generation of this vaccine, called conjugate vaccine, now available, has only 7 serotypes, but it can be administered to infants as young as 2 mo. This is a very important achievement because splenectomized infants are more prone to develop pneumococcal infections than any other group of patients. Conjugate form is administered in a series of 2-3 doses at ages 2, 4, and 6 mo.
Adult
Pediatric
<2 years: Do not administer polyvalent vaccine
>2 years: 0.5 mL IM as primary vaccination
Splenectomy: 0.5 mL IM 1-2 wk before surgery
Booster dose (ie, 0.5 mL IM) usually administered 3-5 y after first dose
May be administered with other vaccines recommended before splenectomy in different syringes and at different sites; immunosuppressive agents (eg, large amounts of corticosteroids, antimetabolites, alkylating agents, cytotoxic agents) may reduce effectiveness; therapy with immunoglobulin preparations is likely to block the active immunity induced with pneumococcal vaccination, withhold for 3 mo after discontinuation of immunoglobulin therapy
Documented hypersensitivity; children <2 y (polyvalent vaccine)
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May cause moderately severe or severe illness with or without fever, arthralgias, urticaria, or Guillain-Barré syndrome (rarely)
Haemophilus influenzae b conjugate vaccine (ActHIB, HibTITER, PedvaxHIB
Recommended 2 wk before splenectomy. Patients who have already received their primary vaccination early in life and also received booster at 12 mo or later are usually protected, even though they may benefit from an additional dose before procedure. Conjugate form administered in a series of 2-3 doses at ages 2, 4, and 6 mo.
Adult
Pediatric
0.5 mL IM before surgery
Corticosteroids or cyclosporine may inhibit full immunologic response
Documented hypersensitivity to any component including thimerosal
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Delay immunization if febrile illness is evident; may cause erythema, swelling, or tenderness; cause-and-effect relationship with observed postvaccine Guillain-Barré syndrome has not been established
Meningococcal vaccine (Menomune A/C/Y/W-135)
Similar to polyvalent pneumococcal vaccine, this is used in children >2 y with risk (eg, complement deficiency, asplenia). Serogroup specific against groups A, C, Y, and W-135 N meningitides.
Adult
Pediatric
<2 years: Do not administer
>2 years: 0.5 mL SC
Administration of immunoglobulin within 1 mo or concurrent administration with immunosuppressive agents may inhibit full immunologic response; coadministration with whole-cell pertussis or whole-cell typhoid vaccines may increase endotoxin content
Documented hypersensitivity; age <2 y; IV/IM/ID administration
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Localized erythema at injection site; asplenic patients with lymphoid tumors who receive either chemotherapy or irradiation respond poorly; avoid during course of acute illness; routine vaccination recommended for high-risk groups (eg, deficiencies in late complement components [C3, C5-C-9], personnel with laboratory or industrial exposure to Neisseria meningitidis aerosols, travelers, residents of hyperendemic areas); for information concerning geographic areas in which vaccination is recommended, contact the Centers for Disease Control and Prevention (404-332-4559); serious adverse reactions should be reported to United States Department of Health and Human Services (1-800-822-7967)
Pneumococcal 7-valent conjugate vaccine (Prevnar)
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 >80% of invasive pneumococcal disease in children <6 y in the United States. Also accounted for 74% of penicillin-nonsusceptible S pneumoniae (PNSP) and 100% of pneumococci with high-level penicillin resistance. Customary age for first dose is 2 mo, but it can be administered to infants as young as 6 wk.
Adult
Not established
Pediatric
3 doses of 0.5 mL IM each at 6-8 wk intervals, followed by a fourth dose of 0.5 mL at age 12-15 mo; recommended dosing interval is 6-8 wk; administer fourth dose 2 mo, or later, following the third dose
Effects may decrease with immunosuppressive agents (eg, immunosuppressive doses of corticosteroids, antimetabolites, alkylating agents, cytotoxic agents); pneumococcal 7-valent conjugate vaccine may increase effects of anticoagulant therapy; globulin preparations may interfere with immune response to pneumococcal vaccine and reduce efficacy (do not administer within 3 mo of vaccine)
Documented hypersensitivity to any component or diphtheria toxoid; severe or moderate febrile illness; thrombocytopenia or coagulation disorder contraindicating IM injection (unless benefits outweigh risks of administration)
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
For IM use only, do not administer IV under any circumstances; take special care to prevent injection into or near a blood vessel or nerve; caution in patients with possible history of latex sensitivity (packaging contains dry natural rubber); use of pneumococcal conjugate vaccine does not replace use of 23-valent pneumococcal polysaccharide vaccination in children aged >24 mo with sickle cell disease, asplenia, HIV infection, chronic illness, or those who are immunocompromised; caution in coagulation disorders
Erythropoiesis
Hydroxyurea was found to induce erythropoiesis and raise Hb levels.20
Hydroxyurea (Hydrea)
Inhibits deoxynucleotide synthesis. S-phase specific nonDNA hypomethylation chemotherapeutic agent. Mechanism of action for thalassemia is unknown but has shown Hb F–inducing activity.
Adult
15 mg/kg/d PO initially (initial dose ranges from 10-20 mg/kg/d); may increase by 5 mg/kg/d q12wk, not to exceed 35 mg/kg/d
Pediatric
Administer as in adults
Coadministration with fluorouracil can increase neurotoxicity; coadministration with didanosine or stavudine may cause fatal pancreatitis and hepatotoxicity; immunization with live virus vaccine may cause severe or fatal infection in immunocompromised patient
Documented hypersensitivity; severe anemia or bone marrow suppression
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in renal impairment; for sickle cell, monitor blood count q2wk and adjust dose accordingly (ie, discontinue if hematologic toxicity occurs, then resume after recovery by reducing dose associated with hematologic toxicity by 2.5 mg/kg/d); hematologic toxicity is defined as neutrophils <2000/mL, platelets <80,000/mL, hemoglobin <4.5 g/dL, and reticulocytes <80,000/mL (if Hbg <9 g/dL)
More on Thalassemia Intermedia |
| Overview: Thalassemia Intermedia |
| Differential Diagnoses & Workup: Thalassemia Intermedia |
 Treatment & Medication: Thalassemia Intermedia |
| Follow-up: Thalassemia Intermedia |
| Multimedia: Thalassemia Intermedia |
| References |
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References
Li Q, Li LY, Mo QH. [A rare thalassemia intermedia case caused by co-existence of Hb H disease (--(SEA)/-alpha(4.2)) and beta-thalassemia major (beta (CD17A)>T/beta (IVS2-654C)>T): implications for prenatal diagnosis]. Nan Fang Yi Ke Da Xue Xue Bao. Jan 2008;28(1):16-9. [Medline].
Haghi M, Feizi AA, Harteveld CL, Pouladi N, Feizi MA. Homozygosity for a rare beta 0-thalassemia mutation [frameshift codons 25/26 (+T)] causes beta-thalassemia intermedia in an Iranian family. Hemoglobin. 2009;33(1):75-80. [Medline].
Harteveld CL, Refaldi C, Cassinerio E, Cappellini MD, Giordano PC. Segmental duplications involving the alpha-globin gene cluster are causing beta-thalassemia intermedia phenotypes in beta-thalassemia heterozygous patients. Blood Cells Mol Dis. May-Jun 2008;40(3):312-6. [Medline].
Finkenstedt A, Bianchi P, Theurl I, Vogel W, Witcher DR, Wroblewski VJ, et al. Regulation of iron metabolism through GDF15 and hepcidin in pyruvate kinase deficiency. Br J Haematol. Mar 2009;144(5):789-93. [Medline].
[Guideline] Gibson BE, Todd A, Roberts I, et al. Transfusion guidelines for neonates and older children. Br J Haematol. Feb 2004;124(4):433-53. [Medline].
Origa R, Galanello R, Ganz T, Giagu N, Maccioni L, Faa G, et al. Liver iron concentrations and urinary hepcidin in beta-thalassemia. Haematologica. May 2007;92(5):583-8. [Medline]. [Full Text].
Cappellini MD, Grespi E, Cassinerio E, Bignamini D, Fiorelli G. Coagulation and splenectomy: an overview. Ann N Y Acad Sci. 2005;1054:317-24. [Medline].
Dunn J, Khan S, Ariff B, Strickland N, Al-Nahhas A. Pulmonary emboli and extramedullary haematopoiesis in beta-thalassaemia intermedia. Nucl Med Rev Cent East Eur. 2008;11(1):34-6. [Medline].
Karimi M, Khanlari M, Rachmilewitz EA. Cerebrovascular accident in beta-thalassemia major (beta-TM) and beta-thalassemia intermedia (beta-TI). Am J Hematol. Jan 2008;83(1):77-9. [Medline].
Morris CR, Gladwin MT, Kato GJ. Nitric oxide and arginine dysregulation: a novel pathway to pulmonary hypertension in hemolytic disorders. Curr Mol Med. Nov 2008;8(7):620-32. [Medline].
Parker TM, Ward LM, Johnston DL, Ventureya E, Klaassen RJ. A case of Moyamoya syndrome and hemoglobin E/beta-thalassemia. Pediatr Blood Cancer. Mar 2009;52(3):422-4. [Medline].
Metarugcheep P, Chanyawattiwongs S, Srisubat K, Pootrakul P. Clinical silent cerebral infarct (SCI) in patients with thalassemia diseases assessed by magnetic resonance imaging (MRI). J Med Assoc Thai. Jun 2008;91(6):889-94. [Medline].
Westerman M, Pizzey A, Hirschman J, et al. Microvesicles in haemoglobinopathies offer insights into mechanisms of hypercoagulability, haemolysis and the effects of therapy. Br J Haematol. Jul 2008;142(1):126-35. [Medline].
Goldschmidt N, Spectre G, Brill A, et al. Increased platelet adhesion under flow conditions is induced by both thalassemic platelets and red blood cells. Thromb Haemost. Nov 2008;100(5):864-70. [Medline].
Singer ST, Ataga KI. Hypercoagulability in sickle cell disease and beta-thalassemia. Curr Mol Med. Nov 2008;8(7):639-45. [Medline].
Aessopos A, Kati M, Farmakis D. Heart disease in thalassemia intermedia: a review of the underlying pathophysiology. Haematologica. May 2007;92(5):658-65. [Medline].
Hankins JS, McCarville MB, Loeffler RB, et al. R2* magnetic resonance imaging of the liver in patients with iron overload. Blood. May 14 2009;113(20):4853-5. [Medline].
Deborah Chirnomas S, Geukes-Foppen M, Barry K, Braunstein J, Kalish LA, Neufeld EJ, et al. Practical implications of liver and heart iron load assessment by T2*-MRI in children and adults with transfusion-dependent anemias. Am J Hematol. Oct 2008;83(10):781-3. [Medline].
Karimi M, Darzi H, Yavarian M. Hematologic and clinical responses of thalassemia intermedia patients to hydroxyurea during 6 years of therapy in Iran. J Pediatr Hematol Oncol. Jul 2005;27(7):380-5. [Medline].
Koren A, Levin C, Dgany O, Kransnov T, Elhasid R, Zalman L, et al. Response to hydroxyurea therapy in beta-thalassemia. Am J Hematol. May 2008;83(5):366-70. [Medline].
Cappellini MD. Long-term efficacy and safety of deferasirox. Blood Rev. Dec 2008;22 Suppl 2:S35-41. [Medline].
Atichartakarn V, Angchaisuksiri P, Aryurachai K, Chuncharunee S, Thakkinstian A. In vivo platelet activation and hyperaggregation in hemoglobin E/beta-thalassemia: a consequence of splenectomy. Int J Hematol. Apr 2003;77(3):299-303. [Medline].
Blendis LM, Modell CB, Bowdler AJ. Some effects of splenectomy in thalassaemia major. Br J Haematol. Sep 1974;28(1):77-87. [Medline].
Sanefuji M, Ohga S, Kira R, et al. Moyamoya syndrome in a splenectomized patient with beta-thalassemia intermedia. J Child Neurol. Jan 2006;21(1):75-7. [Medline].
Cunningham MJ, Macklin EA, Neufeld EJ, et al. Complications of beta-thalassemia major in North America. Blood. Jul 1 2004;104(1):34-9. [Medline].
Davison SM, Kelly DA. Management strategies for hepatitis C virus infection in children. Paediatr Drugs. 2008;10(6):357-65. [Medline].
Aessopos A, Kati M, Meletis J. Thalassemia intermedia today: should patients regularly receive transfusions?. Transfusion. May 2007;47(5):792-800. [Medline].
Gardenghi S, Marongiu MF, Ramos P, et al. Ineffective erythropoiesis in beta-thalassemia is characterized by increased iron absorption mediated by down-regulation of hepcidin and up-regulation of ferroportin. Blood. Jun 1 2007;109(11):5027-35. [Medline].
Lagos P, Lagona E, Kattamis C. Serum ferritin in beta-thalassaemia intermedia. Lancet. Jan 26 1980;1(8161):204-5. [Medline].
Lilleyman JS, Hann IM, Blanchette V. The thalassemia. In: Pediatric Hematology. 2000:316, 325.
Luyendijk W, Went L, Schaad HD. Spinal cord compression due to extramedullary hematopoiesis in homozygous thalassemia. Case report. J Neurosurg. Feb 1975;42(2):212-6. [Medline].
McIntosh N. Beneficial effects of transfusing a patient with non–transfusion-dependent thalassaemia major. Arch Dis Child. Jun 1976;51(6):471-2. [Medline].
Nathan DG, Oski FA. The thalassemia. In: Nathan and Oski's Hematology of Infancy and Childhood. Vol 1. Philadelphia, Pa: WB Saunders Co; 1997:847-9.
Nick H, Acklin P, Lattmann R, et al. Development of tridentate iron chelators: from desferrithiocin to ICL670. Curr Med Chem. Jun 2003;10(12):1065-76. [Medline].
Origa R, Galanello R, Ganz T, et al. Liver iron concentrations and urinary hepcidin in beta-thalassemia. Haematologica. May 2007;92(5):583-8. [Medline].
Pippard MJ, Callender ST, Warner GT, Weatherall DJ. Iron absorption and loading in beta-thalassaemia intermedia. Lancet. Oct 20 1979;2(8147):819-21. [Medline].
Weatherall DJ. Thalassemia. In: Stamatoyannopoulos G, et al, eds. The Molecular Basis of Blood Diseases. Philadelphia, Pa: WB Saunders Co; 1944:157-206.
Weatherall DJ, Clegg JB. The Thalassemia Syndromes. Oxford, England: Blackwell Science Publishing Co; 1981.
Weizer-Stern O, Adamsky K, Amariglio N, et al. Downregulation of hepcidin and haemojuvelin expression in the hepatocyte cell-line HepG2 induced by thalassaemic sera. Br J Haematol. Oct 2006;135(1):129-38. [Medline].
Further Reading
Keywords
beta thalassemia intermedia, β thalassemia intermedia, beta thalassemia major, β thalassemia major, beta thalassemia trait, β thalassemia trait, hemoglobin, Hb, Hb level, globin chain synthesis, erythropoiesis, iron overload, hepcidin, anemia, growth retardation, failure to thrive, bone fractures, enlarged spleen, splenomegaly, pulmonary embolism, pulmonary hypertension, Moyamoya disease, cerebral infarction, enlarged spleen, treatment, diagnosis
