Thalassemia medical therapy

Thalassemia Microchapters
Home
Patient Information
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Thalassemia from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
Diagnostic Study of Choice
History and Symptoms
Physical Examination
Laboratory Findings
Electrocardiogram
X Ray
Echocardiography and Ultrasound
CT
MRI
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Surgery
Primary Prevention
Secondary Prevention
Cost-Effectiveness of Therapy
Future or Investigational Therapies
Case Studies
Case #1
Thalassemia medical therapy On the Web
Most recent articles
Most cited articles
Review articles
CME Programs
Powerpoint slides
Images
American Roentgen Ray Society Images of Thalassemia medical therapy All Images X-rays Echo & Ultrasound CT Images MRI
Ongoing Trials at Clinical Trials.gov
US National Guidelines Clearinghouse
NICE Guidance
FDA on Thalassemia medical therapy
CDC on Thalassemia medical therapy
Thalassemia medical therapy in the news
Blogs on Thalassemia medical therapy
Directions to Hospitals Treating Thalassemia
Risk calculators and risk factors for Thalassemia medical therapy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Shyam Patel [2]

Treatment

Consultation with a Hematologist

The first and most important step in management of a patient with thalassemia is consultation with a hematologist. Thalassemia is a relatively rare condition with intricacies such that a specialist should be involved.

Correction of Nutritional Deficiencies

Concurrent nutritional deficiencies can exacerbate anemia and contribute towards worsening clinical status. Treatment or correction of the underlying deficiencies is highly important to optimize the therapy plan for thalassemia. Such deficiencies include:

• Vitamin B6: This deficiency can be corrected via supplementation with pyridoxine at 100 mg daily. Vitamin B6 is needed for heme synthesis.
• Vitamin B12: This deficiency can be corrected via supplementation with cyanocobalamin at 1000 micrograms daily.
• Folate: This deficiency can be corrected via supplementation with folic acid 1 mg daily. Folate is needed for nucleotide synthesis and red blood cell production.

Transfusion Support

Red blood cell transfusions is a mainstay of therapy for thalassemia. Red blood cell transfusion restores hemoglobin toward a normal range. On average, one unit of packed red blood cells will increase a patient's hemoglobin by 1 gram per deciliter. One unit of packed red blood cells contains 200mg of iron. Of note, packed red blood cell transfusion is a supportive measure and does not alter the course of the disease. However, given that there are no known effective disease-modifying therapies for thalassemia, red blood cell transfusions are frequently considered as the main type of therapy.

Bone Marrow Transplant

Bone marrow transplant has shown promise with some patients of thalassemia major. Successful transplant can eliminate the patients dependencies on transfusions. Thalassemia intermedia patients vary a lot in their treatment needs depending on the severity of their anemia.

Anti-Oxidant Therapy

The antioxidant indicaxanthin, found in beets, in a spectrophotometric study showed that indicaxanthin can reduce perferryl-Hb generated in solution from met-Hb and hydrogen peroxide, more effectively than either Trolox or Vitamin C. Collectively our results demonstrate that indicaxanthin can be incorporated into the redox machinery of β-thalassemic RBC and defend the cell from oxidation, possibly interfering with perferryl-Hb, a reactive intermediate in the hydroperoxide-dependent Hb degradation. However, there is no strong supportive evidence for the efficacy of anti-oxidants in thalassemia, given that this is not a disease characterized by oxidative stress.

Hydroxyurea

Recently, increasing reports suggest that up to 5% of patients with beta-thalassemias produce fetal hemoglobin (HbF), and use of hydroxyurea also has a tendency to increase the production of HbF, by as yet unexplained mechanisms. Hydroyurea is also used in sickle cell anemia to help increase fetal hemoglobin production. This improves the oxygen carrying capacity of blood.

Gene therapy

Beta-globin gene therapy has been proposed for treatment of thalassemias. This concept is based on the idea that restoration of normal globin gene function can treat the disease. The proposed in vitro systems include embryonic stem cells (ESCs) and induced pluripotent stem cells (iPS cells), as these cells can give rise to daughter cells that propagate the normal globin gene. Alternatively, ex vivo lentiviral transduction of hematopoietic stem cells can be done.PMC4779296

• Embryonic stem cells: Early phase of hematopoiesis have been studies in ESCs. These are totipotent cells, meaning that they can give rise to all tissue types within the body. In order to generate this model system, a blastocyst is generated, and ESCs are isolated from the inner cell mass. After formation of embryoid bodies, these cells can be used for tissue generation. Each resulting tissue contains cells with the normal globin gene, without the thalassemia mutation.
• Inducible pluripotent stem cells: The discovery of iPS cells by Yamanaka's group paved the way for downstream scientific applications for stem cell therapy for diseases. iPS cells are generated by retroviral transduction of stem cell transcription factors such as Oct4, Sox2, c-Myc, and KLF4 into differentiated cell types. The factors allow for the differentiated cell types to become reprogrammed into stem cells, which then have the ability to give rise to all cells of the body. iPS cells from patients may thus be therapeutic for patients with thalassemias, as alpha-globin and beta-globin production can be restored.
• Retroviral vectors: Gamma-retroviral vectors and lentiviral vectors have been used to introduce normal globin genes into cells. An exogenous globin gene is encoded in these viruses, and the viruses are then used to transfect cells. Rapamycin can be used to increase the lentiviral transduction efficiency. Additional methods can be used to prevent silencing of the transgenes. These methods include use of chromatin accessibility elements and insulators in the viral vectors.
• Hemoglobin F inducers: These are chemical agents that can increase HbF production. These work in synergy with gene therapy for thalassemias.

Treatment of Complications

• Iron overload: The frequent use of blood transfusions poses a significant problem to the treatment of thalassemia. Beginning at the age of 10, iron levels should be monitored.
  • Limitation to the number of transfusions: Cautious use of blood transfusions is an important initial step to combat iron overload. The typical hemoglobin threshold for transfusion is 7 g/dl. Below this threshold, it is reasonable to administer a blood transfusion.
  • Deferasirox: This is an iron chelator.
  • Deferoxamine: This is an iron chelator.
  • Deferiprone: This is an iron chelator.PMC3757270
• Tmprss6 silencing: Tmprss6 is an enzyme that functions to inhibit hepcidin, which is a liver protein that induces iron deficiency. Silencing of Tmprss6 via RNA interference has been proposed to treat iron overload via regulation of hepcidin.PMC3655736 Preclinical studies in mice have shown efficacy for Tmprss6 silencing for treatment of iron overload via upregulation of hepcidin. This strategy has also been shown to be efficacious in mice with hemochromatosis, a state of iron overload.
• Dietary modifications: Patients with thalassemia who develop iron overload should be counseled about dietary measures that can be taken to prevent the risk of iron overload. Certain foods, such as red meats, should be avoided given their high iron content. Vitamin C should be limited, as vitamin C enhanced iron absorption.

Contraindicated medications

Thalassemia is considered an absolute contraindication to the use of the following medications:

• Pegylated interferon alfa-2b