eMedicine Specialties > Pediatrics: General Medicine > Hematology

Thalassemia Intermedia: Follow-up

Author: Hassan M Yaish, MD, Professor of Pediatrics, University of Utah School of Medicine; Director of Hematology Services, Medical Director, Mountain States Hemophilia and Thrombophilia Treatment Center; Pediatric Hematologist/Oncologist, Department of Pediatrics, Primary Children's Medical Center
Contributor Information and Disclosures

Updated: Sep 29, 2009

Follow-up

Further Inpatient Care

  • Most medical care in thalassemia intermedia is provided in an outpatient setting. Inpatient care is reserved for surgical procedures such as splenectomy or resection of large extramedullary hematopoietic tumor-like masses compressing vital organs, infectious complications, or in rare severe cases that are treated by a bone marrow transplant.

Further Outpatient Care

  • Frequent outpatient visits are needed in the early stages to monitor hematologic parameters, activity, exercise tolerance, growth, and development of bone changes.
  • Once the patient requires regular transfusions, monthly outpatient visits for blood transfusions and laboratory work for monitoring iron load status are usually required. Guidelines for transfusion in neonates and older children have been established.5
  • While receiving chelation therapy, patients should have eye examinations and hearing tests as part of monitoring for the complications of therapy.

Deterrence/Prevention

  • Prevention of thalassemia intermedia is based on public education, family counseling, and widespread measures, such as screening before marriage in high-risk populations, similar to those recommended for thalassemia in general.

Complications

  • Most complications expected in thalassemia intermedia have been described in other sections. The conversion of thalassemia intermedia to a transfusion-dependent state is, by itself ,the most serious complication because that marks the transition of thalassemia intermedia to a more severe form of β thalassemia.
  • As a result of the advanced care provided to patients with thalassemia, they are now surviving to an advanced age. With this longer survival comes new problems, which require a change in the approach to the care of affected patients. Three such complications have recently been described as major issues in the adults with thalassemia.
    • Hepatitis C virus (HCV) infection is a major complication of the lifelong blood transfusions in patients with the severe forms of thalassemia. This is probably less of a problem in patients with thalassemia intermedia who are not transfusion dependent. Nevertheless, HCV has also been reported in patients with thalassemia who have never had transfusions.
      • The incidence of positive HCV antibodies or RNA in patients aged 25 years or older (who were treated before the screening for HCV was initiated in 1990) was reported by the Thalassemia Clinical Research Network (TCRN) to be as high as 70% compared with only 5% in patients aged 15 years or younger.25 The American Association of Blood Banks (AABB) has reported that the chance to contract HCV from blood transfusions in the United States is 1 per 1 million units transfused. Unfortunately, this is not the case in some developing countries where the rate was reported to be 63.8%.
      • HCV and iron overload are risk factors for cirrhosis and hepatocellular carcinoma (HCC); for this reason, many recommend to monitor such patients closely with liver ultrasonography and alpha fetoprotein level (AFP). About 33% of patients with HCV in North America are expected to spontaneously clear the virus; if this does not occur, aggressive treatment should be initiated. Pegylated interferon alpha (INF-alpha), in combination with Ribavirin, has been very effective in treating children with HCV infection.26
    • Thrombotic events have been increasingly encountered not only in patients with thalassemia intermedia but also in those with thalassemia major and β thalassemia/Hb E disease. In one study of 85 patients with thalassemia intermedia and 65 with thalassemia major, the incidence of venous thromboembolic events was 29% and 2%, respectively. Twenty-three of the 24 patients with thalassemia intermedia and venous thromboembolic events had undergone splenectomy. For this reason, some recommend short-term antithrombotic therapy both perioperatively and when a risk factor for thrombosis exists. A low-dose daily aspirin is also recommended for all patients with thalassemia who are splenectomized and for those with thalassemia major and a platelet count of 600,000/m L after splenectomy.
    • Fertility in adult patients with thalassemia is another new issue that providers have to deal with.
  • Severe thalassemia is often characterized by hypersplenism, which usually results in exaggerated anemia, thrombocytopenia, and enlarged abdomen.
  • Iron overload, liver disease, and cardiac and endocrine defects are also encountered in this condition.
  • Bone deformities, fractures, and neurologic complications from compression by tumorlike extramedullary hematopoietic tissue masses are more frequently observed in thalassemia intermedia than in thalassemia major because the hyperactivity of the marrow in patients with untreated thalassemia intermedia is not suppressed by repeated blood transfusions.
  • Complications of blood transfusions, such as hepatitis and other transmitted organisms, are all well known.

Prognosis

  • Patients with milder cases have good prognosis; however, after several years of stable disease, many patients develop the severe form and become transfusion dependent. Patients with the severe forms have the same prognosis as those with thalassemia major.
  • In most cases, the transformation from the stable state to the transfusion-dependent state is usually gradual. A patient with an Hb of 7-8 g/dL for a long time may drop to 6 g/dL or less. In this case, and in the closely monitored patient, the drop is frequently attributed to a viral infection or transient cause. A single blood transfusion is usually recommended, and the patient is closely monitored. In many occasions, the patient's status continues as before, and no more blood is needed for the time.
  • However, in other patients, a month or so after the transfusion, the Hb drops again and, at this time, the spleen (which has been enlarged all along) is now larger or more active; therefore, splenectomy is usually considered. Many patients respond well to the procedure and require no more blood for the time being. However, others maintain good Hb for several months or longer before developing the severe anemia again. At this time, the need for regular blood transfusions becomes clear; close monitoring for iron overload followed by chelation therapy when indicated should be undertaken. For this reason, all patients with thalassemia intermedia should be closely monitored in anticipation for developing such changes, which require immediate action.

Patient Education

  • Education of the population at risk is the most effective prevention method. Measures similar to those undertaken in certain parts of Europe have been very effective in decreasing the numbers of patients with thalassemia in general (see Thalassemia, Beta).
  • Even in developing countries, massive education about thalassemia has changed the outlook and provided local people a great incentive to do whatever is necessary to eliminate the condition or at least minimize its severity.

Miscellaneous

Medicolegal Pitfalls

  • The diagnosis of thalassemia intermedia is purely clinical and is usually made after a period of observation to determine that the patient is able to maintain a satisfactory Hb level for a long time without the need for blood transfusions. If the physician settles for a marginal level of hemoglobin (Hb) and decides not to initiate blood transfusion therapy, the patient's Hb level may fluctuate and decrease further, potentially reaching a very low level if the patient is not closely monitored. Should this occur, permanent damage, including heart failure, bone deformity, hypersplenism, liver damage, or other complications, may occur. In otherwise similar circumstances, patients with marginally severe disease should be treated in the same way as patients with thalassemia major to avoid medicolegal actions that may leave the provider liable.
  • In prenatal diagnosis of thalassemia intermedia, DNA probes of known genotypes are usually used. Because this condition varies significantly in severity (despite the misleading name), a milder form of disease may be anticipated in a baby who turns out to be affected by a more severe form of the disease. For this reason, parents should be informed in advance that testing may help rule out the possibility of severe disease (such as when a heterozygous condition is diagnosed) or may confirm severe disease when a homozygosity or heterozygosity for 2 severe mutations is confirmed. However, intermediate cases may be misleading, and the predictability is much less accurate.
  • Increased absorption of iron in all forms of thalassemia results in hemosiderosis or iron overload regardless of whether the patient is receiving regular blood transfusions. Failure to monitor for or recognize this may end in significant organ damage. For this reason, close monitoring of iron status, ferritin level, and liver function tests is needed for evaluation. When in doubt about whether iron levels in the patient's tissues are sufficient to initiate chelation, a deferoxamine challenge test with measurement of urinary iron excreted is appropriate.
 


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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Further Reading

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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

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Contributor Information and Disclosures

Author

Hassan M Yaish, MD, Professor of Pediatrics, University of Utah School of Medicine; Director of Hematology Services, Medical Director, Mountain States Hemophilia and Thrombophilia Treatment Center; Pediatric Hematologist/Oncologist, Department of Pediatrics, Primary Children's Medical Center
Hassan M Yaish, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Michigan State Medical Society, and New York Academy of Sciences
Disclosure: Nothing to disclose.

Medical Editor

J Martin Johnston, MD, Associate Professor of Pediatrics, Mercer University School of Medicine; Director of Pediatric Hematology/Oncology, Backus Children's Hospital; Consulting Oncologist/Hematologist, St Damien's Pediatric Hospital
J Martin Johnston, MD is a member of the following medical societies: American Society of Pediatric Hematology/Oncology
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

James L Harper, MD, Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Assistant Clinical Professor, Department of Pediatrics, Creighton University; Director, Continuing Medical Education, Children's Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center
James L Harper, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Federation for Clinical Research, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Council on Medical Student Education in Pediatrics, and Hemophilia and Thrombosis Research Society
Disclosure: Nothing to disclose.

CME Editor

Helen SL Chan, MBBS, FRCP(C), FAAP, Senior Scientist, Research Institute; Professor, Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Canada
Helen SL Chan, MBBS, FRCP(C), FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Society of Hematology, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Chief Editor

Robert J Arceci, MD, PhD, King Fahd Professor of Pediatric Oncology, Professor of Pediatrics, Oncology and the Cellular and Molecular Medicine Graduate Program, Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine
Robert J Arceci, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Pediatric Society, American Society of Hematology, and American Society of Pediatric Hematology/Oncology
Disclosure: Nothing to disclose.

 
 
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