Thalassemia

Definition Thalassemia are forms of inherited autosomal recessive blood disorders that originated in the Mediterranean region. In thalassemia, the disease is caused by the weakening and destruction of red blood cells. Thalassemia is caused by variant or missing genes that affect how the body makes hemoglobin. Hemoglobin is the protein in red blood cells that carries oxygen. People with thalassemia make less hemoglobin and fewer circulating red blood cells than normal, which results in mild or severe anemia. Thalassemia will be present as microcytic anemia which may be differentiated from iron deficiency anemia using the mentzer index calculation. Types of thalassemia and HBA2,[9] inherited in a Mendelian recessive fashion. There are two gene locii and so four alleles. It is also connected to the deletion of the 16p chromosome. Thalassemias result in decreased al pha-globin production, therefore fewer alpha-globin chains are produced, resulting in an excess of chains in adults and excess chains in newborns. The excess chains form unstable tetramers (called Hemoglobin H or HbH of 4 beta chains), which have abnormal oxygen dissociation curves. Four
Alpha Thalassemia - The thalassemias involve the genes HBA1
[8]

genes are involved in making the alpha hemoglobin chain. You get two from each of your parents. If you inherit:

One mutated gene, you'll have no signs or symptoms of thalassemia. But, you're a carrier of the disease and can pass it on to your children.

Two mutated genes, your thalassemia signs and symptoms will be mild. This condition may be called alpha-thalassemia minor, or you may be told you have an alpha-thalassemia trait.

Three mutated genes, your signs and symptoms will be moderate to severe. This condition is also called hemoglobin H disease.

Four mutated genes, the condition is called alpha-thalassemia major or hydrops fetalis. It usually causes a fetus to die before delivery or a newborn to die shortly after birth.

Beta Thalassemia - (-thalassemias) are a group of inherited blood disorders caused by reduced or absent synthesis of the beta chains of hemoglobin resulting in variable phenotypes ranging from severe anemia to clinically asymptomatic individuals. Individuals with beta thalassemia major usually present within the first two years of life with severe anemia, poor growth, and skeletal abnormalities during infancy. Affectedchildren will require regular lifelong blood transfusions.
Types Any given individual has two globin alleles: Name Description Alleles

Thalassemia minor

Only one of globin alleles bears a mutation. Individuals will suffer from microcytic anemia. Detection usually involves lower than normal MCV value (<80 fL). Plus an increase in fraction of Hemoglobin A2 (>3.5%) and a decrease in fraction of Hemoglobin A(<97.5%).

+/ or o/

Thalassemia intermedia

A condition intermediate between the major and minor forms. Affected individuals can often manage a normal life but may need occasional +/+or transfusions, e.g., at times of illness or pregnancy, depending on the severity of o/+ their anemia.

Thalassemia major

If both alleles have thalassemia mutations. This is a severe microcytic, hypochromic anemia. Untreated, it causes anemia,splenomegaly, and severe bone deformities. It progresses to death before age 20. Treatment consists of periodic blood transfusion; splenectomy if splenomegaly is present, and treatment of transfusion-caused iron overload. Cure is possible by bone marrow transplantation. Cooley's anemia is named after Thomas Benton Cooley.[12]

o/o

Delta Thalassemia - is a form of thalassemia. It is associated with HBD. Thalassemia Statistics Incidence of Beta thalassemia in the Philippines is relatively low (approx <1%) The alpha and beta thalassaemias are the most common inherited single-gene disorders in the world with the highest prevalence in areas where malaria was or still is endemic.

Pathophysiology Alpha Thalassemia - thalassemias result in decreased alpha-globin production, therefore fewer alpha-globin chains are produced, resulting in an excess of chains in adults and excess chains in newborns. The excess chains form unstable tetramers (called Hemoglobin H or HbH of 4 beta chains) which have abnormal oxygen dissociation curves. The excess chains form tetramers which are poor carriers of O2 since their affinity for O2 is too high so it is not dissociated in the periphery. Homozygote 0 thalassaemias, where there is lots of 4 but no globins at all (referred to as Hb Barts), often result in still birth.

Beta Thalassemia - thalassemia occurs when there is a quantitative reduction of globin chains that are usually structurally normal.2 They are caused by mutations that nearly all affect the globin locus and are extremely heterogeneous. Almost every possible defect affecting gene expression at transcription or post-transcriptional level, including translation, have been identified in thalassemia.3 These genetic defects lead to a variable reduction in globin output ranging from a minimal deficit (mild + thalassemia alleles) to complete absence ( thalassemia). In thalassemia, the synthesis of normal globin chains from the unaffected globin genes continues as normal, resulting in the accumulation within the erythroid precursors of excess unmatched globin. The free globin chains are not able to form viable tetramers and instead precipitate in the red cell precursors in the bone marrow forming inclusion bodies. These chain inclusions can be demonstrated by both light and electron microscopy in the erythroid precursors in the bone marrow as well as in the peripheral red cells following splenectomy. They are responsible for the extensive intramedullary destruction of the erythroid precursors and hence the ineffective erythropoiesis that underlies all thalassemias. Anemia in thalassemia thus results from a combination of ineffective erythropoiesis, peripheral hemolysis, and an overall reduction in hemoglobin synthesis. The severity of disease in thalassemia correlates well with the degree of imbalance between and non - globin chains and the size of the free chain pool. Thus, factors that reduce the degree of chain imbalance and the magnitude of chain excess in the red cell precursors will have an impact on the phenotype. Signs and Symptoms Fatigue Weakness Shortness of breath Pale appearance Irritability

Yellow discoloration of skin (jaundice) Facial bone deformities Slow growth Abdominal swelling Dark urine

The signs and symptoms you experience depend on the type and severity of thalassemia you have. Some babies show signs and symptoms of thalassemia at birth, while others may develop signs or symptoms during the first two years of life. Some people who have only one affected hemoglobin gene don't experience any thalassemia symptoms. Test and Diagnosis Most children with moderate to severe thalassemia show signs and symptoms within their first two years of life. If your doctor suspects your child has thalassemia, he or she may confirm a diagnosis using blood tests. If your child has thalassemia, blood tests may reveal: A low level of red blood cells Smaller than expected red blood cells Pale red blood cells Red blood cells that are varied in size and shape Red blood cells with uneven hemoglobin distribution, which gives the cells a bull's-eye appearance under the microscope

Blood tests may also be used to: Measure the amount of iron in your child's blood Evaluate his or her hemoglobin Perform DNA analysis to diagnose thalassemia or to determine if a person is carrying mutated hemoglobin genes

Medications
Multiple blood transfusions can result in iron overload. The iron overload related to thalassemia may be treated via chelation therapy with the medications deferoxamine , deferiprone or deferasirox. These treatments have resulted in improved life expectancy in those with thalassemia major.

Desferoxamine is only effective via daily injections which makes its long term use more difficult. It has the benefit of being inexpensive and decent long term safety. Adverse effects are primary skin reactions around the injection site and hearing loss. Desferasirox has the benefit of being an oral medication. Common side effects include: nausea, vomiting and diarrhea. It however is not effective in everyone and is probably not suitable in those with significant cardiac issues related to iron overload. The cost is also significant. Deferiprone is given as an oral medication. Nausea, vomiting and diarrhea is relatively common with its use. While available in Europe as of 2010 it is not available in North America. It appears to be the most effective agent when the heart is significantly involved. Management Treatment for moderate to severe thalassemia: Frequent blood transfusions. More-severe forms of thalassemia often require frequent blood transfusions, possibly every few weeks. Over time, blood transfusions cause a buildup of iron in your blood, which can damage your heart, liver and other organs. To help your body get rid of the extra iron, you may need to take medications that rid your body of extra iron. Stem cell transplant. Also called a bone marrow transplant, a stem cell transplant may be used to treat severe thalassemia in select cases. Prior to a stem cell transplant, you receive very high doses of drugs or radiation to destroy your diseased bone marrow. Then you receive infusions of stem cells from a compatible donor. However, because these procedures have serious risks, including death, they're generally reserved for people with the most severe disease who have a well-matched donor available usually a sibling. Nursing Interventions Measure the pressure to minimize the complications associated with physical and emotional stress Provide an adequate diet Encourage the patient to drink plenty of fluids. Provide emotional support Help the patient and his family cope for chronic nature of Thalassemia Watch for adverse reactions during and after RBC transfusions. Collaborative an antibiotic, and observe the patient for adverse reactions. Explain the need for lifelong transfusions.

Nursing diagnosis
* Deficient knowledge (treatment regimen) *Delayed growth and development * Disturbed body image * Ineffective tissue perfusion: Cardiopulmonary * Interrupted family processes * Activity intolerance * Risk for infection

Activity intolerance R/T impaired oxygen transport High risk for infection R/T decreased resistance secondary to hypoxia Altered body image R/T skeletal changes High risk for altered health maintenance R/T lack of knowledge