Beta thalassaemia in children

Hematology

Clinicals - History

Fact Explanation
An inherited hemoglobinopathy This is an autosomal recessively inherited condition. Alteration in the globin chain production of either alpha or Beta can cause Thalassemia and when the β chain production is low, it's called β thalassemia. b-like globin genes are arranged in chromosome 11. Symptoms may not be evident until the 6-8 months of life as Hemoglobin F production occurs with production of γ-globin instead of beta chains. An inherited hemoglobinopathy
This is an autosomal recessively inherited condition. Alteration in the globin chain production of either alpha or Beta can cause Thalassemia and when the β chain production is low, it's called β thalassemia. b-like globin genes are arranged in chromosome 11. Symptoms may not be evident until the 6-8 months of life as Hemoglobin F production occurs with production of γ-globin instead of beta chains.
Asymptomatic Silent carriers and most patients with thalassemia traits also have no signs or symptoms and usually diagnosed when RBC indices are low and when there's hypochromic microcytic anemia that does not respond to iron supplementation. Asymptomatic
Silent carriers and most patients with thalassemia traits also have no signs or symptoms and usually diagnosed when RBC indices are low and when there's hypochromic microcytic anemia that does not respond to iron supplementation.
Shortness of breath on exertion, increased fatigue, suggestive of anemia Accumulation of α chains in the deficiency of beta chains in the RBC precursors causes intramedullary destruction of these cells and red blood cells in the circulation with excess alpha chains undergo hemolysis. Anemia in the person with β thalassemia are caused by both hemolysis and ineffective erythropoiesis. Shortness of breath on exertion, increased fatigue, suggestive of anemia
Accumulation of α chains in the deficiency of beta chains in the RBC precursors causes intramedullary destruction of these cells and red blood cells in the circulation with excess alpha chains undergo hemolysis. Anemia in the person with β thalassemia are caused by both hemolysis and ineffective erythropoiesis.
Yellowish discolration of the sclera This is due to hemolytic process which results in increased production of bilirubin which gets deposited in the sclera. Yellowish discolration of the sclera
This is due to hemolytic process which results in increased production of bilirubin which gets deposited in the sclera.
Slight enlargement of the abdomen Increased extramedullary hemopoiesis in the spleen cause splenic enlargement. Slight enlargement of the abdomen
Increased extramedullary hemopoiesis in the spleen cause splenic enlargement.
Frontal bossing and charesteristic facies ineffective erythropoiesis in the bone causes expansion of the marrow and these bone changes. Frontal bossing and charesteristic facies
ineffective erythropoiesis in the bone causes expansion of the marrow and these bone changes.
Fever and poor growth Poor growth in patients with thalassemia could be due to involvement of endocrine organs in iron overload as well as due to chronicity of the disease. Fever and poor growth
Poor growth in patients with thalassemia could be due to involvement of endocrine organs in iron overload as well as due to chronicity of the disease.
Acute loin to groin pain with hematuria Hyperuricemia can occur as there's increased cell turn over due to hemolysis and kidney stones can result. Acute loin to groin pain with hematuria
Hyperuricemia can occur as there's increased cell turn over due to hemolysis and kidney stones can result.
Bleeding tendency This complication results from iron overload due to increased iron absorption as well as due to multiple transfusions. Many internal organs are affected especially liver. Liver dysfunction results in reduced production of coagulation factors and low platelets with bleeding tendency. Bleeding tendency
This complication results from iron overload due to increased iron absorption as well as due to multiple transfusions. Many internal organs are affected especially liver. Liver dysfunction results in reduced production of coagulation factors and low platelets with bleeding tendency.
Slate grey discoloration of the skin This is due to iron deposition in the skin Slate grey discoloration of the skin
This is due to iron deposition in the skin
Increased thirst, urination and weight loss These symptoms result from diabetes mellitus due to deposition of iron in the pancreas Increased thirst, urination and weight loss
These symptoms result from diabetes mellitus due to deposition of iron in the pancreas
Delayed puberty This is due to iron deposition in the pitiutary and endocrine organs such as Thyroid gland. Delayed puberty
This is due to iron deposition in the pitiutary and endocrine organs such as Thyroid gland.
Chest pain, palpitations This is due to iron deposition in the heart resulting in cardiomyopathy causing chest pain and rhythm disturbances. Chest pain, palpitations
This is due to iron deposition in the heart resulting in cardiomyopathy causing chest pain and rhythm disturbances.

Clinicals - Examination

Fact Explanation
No signs Silent carriers and most patients with thalassemia traits also have no signs or symptoms and usually diagnosed when RBC indices are low and when there's hypochromic microcytic anemia that does not respond to iron supplementation. No signs
Silent carriers and most patients with thalassemia traits also have no signs or symptoms and usually diagnosed when RBC indices are low and when there's hypochromic microcytic anemia that does not respond to iron supplementation.
Pallor, Icterus and Splenomegaly in infancy Symptoms usually appear when there's conversion of Hb F to Hb A (in which gamma chains are replaced with beta chains) at aroung 6-8 months of life. A thalassemic infant typically presents with pallor due to anemia, icterus and splenomegaly. Pallor, Icterus and Splenomegaly in infancy
Symptoms usually appear when there's conversion of Hb F to Hb A (in which gamma chains are replaced with beta chains) at aroung 6-8 months of life. A thalassemic infant typically presents with pallor due to anemia, icterus and splenomegaly.
Pallor Accumulation of α chains in the deficiency of beta chains in the RBC precursors causes intramedullary destruction of these cells and red blood cells in the circulation with excess alpha chains undergo hemolysis. Anemia in the person with β thalassemia are caused by both hemolysis and ineffective erythropoiesis Pallor
Accumulation of α chains in the deficiency of beta chains in the RBC precursors causes intramedullary destruction of these cells and red blood cells in the circulation with excess alpha chains undergo hemolysis. Anemia in the person with β thalassemia are caused by both hemolysis and ineffective erythropoiesis
Icterus This is due to hemolytic process which results in increased production of bilirubin which gets deposited in the sclera. Icterus
This is due to hemolytic process which results in increased production of bilirubin which gets deposited in the sclera.
Charesteristic facies such as frontal bossing, prominent facial bones, and dental malocclusion Increased erythropoiesis in the bone causes expansion of the marrow and these bone changes. Charesteristic facies such as frontal bossing, prominent facial bones, and dental malocclusion
Increased erythropoiesis in the bone causes expansion of the marrow and these bone changes.
Massive splenomegaly Increased extramedullary hemopoiesis in the spleen cause splenic enlargement. Massive splenomegaly
Increased extramedullary hemopoiesis in the spleen cause splenic enlargement.
Hepatomegaly This results from iron overload due to increased iron absorption as well as due to multiple transfusions. Many internal organs are affected especially liver. Liver can be enlarged due to extramedullary hemopoiesis as well. Hepatomegaly
This results from iron overload due to increased iron absorption as well as due to multiple transfusions. Many internal organs are affected especially liver. Liver can be enlarged due to extramedullary hemopoiesis as well.
Slate grey discoloration of the skin This is due to iron deposition in the skin Slate grey discoloration of the skin
This is due to iron deposition in the skin
Growth retardation Poor growth in patients with thalassemia could be due to involvement of endocrine organs in iron overload as well as due to chronicity of the disease. Growth retardation
Poor growth in patients with thalassemia could be due to involvement of endocrine organs in iron overload as well as due to chronicity of the disease.
Heart murmer and Signs of heart failure such as Cardiomegaly, Gallop rhythm, Bilateral inspiratory crepiations This is due to iron deposition in the heart resulting in cardiomyopathy causing chest pain and rhythm disturbances abd subsequent heart failure Heart murmer and Signs of heart failure such as Cardiomegaly, Gallop rhythm, Bilateral inspiratory crepiations
This is due to iron deposition in the heart resulting in cardiomyopathy causing chest pain and rhythm disturbances abd subsequent heart failure
Paralysis, Neuropathy Large extramedullary hematopoietic masses in the spine can compress the nerves and cause neuropathy Paralysis, Neuropathy
Large extramedullary hematopoietic masses in the spine can compress the nerves and cause neuropathy
Transfusion marks over the abdomen This is due to iron chelation therapy with subcutaneous chelating agents. These injections are usually given around the umbilicus and can be seen as a feature of good compliance to chelation therapy. Transfusion marks over the abdomen
This is due to iron chelation therapy with subcutaneous chelating agents. These injections are usually given around the umbilicus and can be seen as a feature of good compliance to chelation therapy.

Investigations - Diagnosis

Fact Explanation
Full blood count Hemoglobin count is low. Both MCV(Mean corpuscular volume) and MCH (mean corpuscular Hb) are very low. Remarkably RDW is very high due to presence of cells of various sizes and shapes. Platelet count is usually normal but splenomegaly can cause low counts. Full blood count
Hemoglobin count is low. Both MCV(Mean corpuscular volume) and MCH (mean corpuscular Hb) are very low. Remarkably RDW is very high due to presence of cells of various sizes and shapes. Platelet count is usually normal but splenomegaly can cause low counts.
Blood picture This shows hypochromatic microcytic cells with reticulocytosis, nucleated RBCs and basophilic stippling. Occaional target cells can be seen as well. Blood picture
This shows hypochromatic microcytic cells with reticulocytosis, nucleated RBCs and basophilic stippling. Occaional target cells can be seen as well.
Hemoglobin electrophoresis This confirms the diagnosis of thalassemia. This shows elevated Hb F fraction in patients with β thalassemia. Hb A is not present and only Hb A2 and Hb F are seen. Hemoglobin electrophoresis
This confirms the diagnosis of thalassemia. This shows elevated Hb F fraction in patients with β thalassemia. Hb A is not present and only Hb A2 and Hb F are seen.
High Performance Liquid Chromatography (HPLC) This also confirms Thalassemia and it gives a quick diagnosis than Hb electrophoresis and only needs a small amount of blood. High Performance Liquid Chromatography (HPLC)
This also confirms Thalassemia and it gives a quick diagnosis than Hb electrophoresis and only needs a small amount of blood.
Serum iron studies- Serum iron, Serum Ferritin, Total iron binding capacity Are usually normal unless there's iron overload. This is usually done to exclude iron deficiency anemia. Serum iron studies- Serum iron, Serum Ferritin, Total iron binding capacity
Are usually normal unless there's iron overload. This is usually done to exclude iron deficiency anemia.
Skeletal x-rays The classic "hair on end" appearance of the skull x-ray with expansion of the marrow with marked thinning the cortex is seen. Skeletal x-rays
The classic "hair on end" appearance of the skull x-ray with expansion of the marrow with marked thinning the cortex is seen.

Investigations - Management

Fact Explanation
Full blood count To assess the Hemoglobin count and to plan the transfusion and also to monitor the effects of deferoxamine (DFO) therapy such as agranulocytosis, neutropenia, thrombocytopenia and worsening anemia. Full blood count
To assess the Hemoglobin count and to plan the transfusion and also to monitor the effects of deferoxamine (DFO) therapy such as agranulocytosis, neutropenia, thrombocytopenia and worsening anemia.
Serum iron studies- Serum Ferritin, Serum Iron, Total iron binding capacity The serum ferritin level is frequently used to monitor the status of iron overload. Serum iron studies- Serum Ferritin, Serum Iron, Total iron binding capacity
The serum ferritin level is frequently used to monitor the status of iron overload.
Thyroid function tests Hypothyroidism can occur due to deposition of iron in the thyroid gland therefore thyroid functions are monitored. Thyroid function tests
Hypothyroidism can occur due to deposition of iron in the thyroid gland therefore thyroid functions are monitored.
CT scan- abdomen As a non invasive method to assess the hepatomegaly for iron overload in patients receiving chelation therapy. CT scan- abdomen
As a non invasive method to assess the hepatomegaly for iron overload in patients receiving chelation therapy.
MRI scan- abdomen As a non invasive method to assess the hepatomegaly for iron overload in patients receiving chelation therapy. MRI scan- abdomen
As a non invasive method to assess the hepatomegaly for iron overload in patients receiving chelation therapy.
Liver function tests To assess the liver finctions for iron overload Liver function tests
To assess the liver finctions for iron overload
Per cutaneous liver biopsy Liver biopsy is used to measure the iron content in the liver per gram of tissue Per cutaneous liver biopsy
Liver biopsy is used to measure the iron content in the liver per gram of tissue
Chest X-ray Cardiac size and shape is evaluated as iron is deposited in the heart Chest X-ray
Cardiac size and shape is evaluated as iron is deposited in the heart
Cardiac T2-MRI This does not correlate well with serum ferritin or either echocardiography findings but this is non invasive method to detect iron deposition in the heart. Cardiac T2-MRI
This does not correlate well with serum ferritin or either echocardiography findings but this is non invasive method to detect iron deposition in the heart.
Electrocardiogram To assess the cardiac function in a patient having cardiomyopathy due to iron over load Electrocardiogram
To assess the cardiac function in a patient having cardiomyopathy due to iron over load
Echocardiography To assess the cardiac function in a patient having cardiomyopathy due to iron over load Echocardiography
To assess the cardiac function in a patient having cardiomyopathy due to iron over load
Eye examination by Ophthalmoscopy and slit lamp examination To monitor the effects on the eye such as lens opacities, cataracts, elevations in intraocular pressure, and retinal disorders after deferoxamine (DFO) therapy and the administration of other chelating agents Eye examination by Ophthalmoscopy and slit lamp examination
To monitor the effects on the eye such as lens opacities, cataracts, elevations in intraocular pressure, and retinal disorders after deferoxamine (DFO) therapy and the administration of other chelating agents
Hearing tests To monitor the effects on hearing such as high frequency hearing loss after deferoxamine (DFO) therapy and the administration of other chelating agents Hearing tests
To monitor the effects on hearing such as high frequency hearing loss after deferoxamine (DFO) therapy and the administration of other chelating agents
Renal function tests to monitor the effects of deferoxamine (DFO) therapy such as dose related increases in serum creatinine Renal function tests
to monitor the effects of deferoxamine (DFO) therapy such as dose related increases in serum creatinine
Fasting blood sugar Iron deposition in the pancreas can cause diabetes and to detect, this is done. Fasting blood sugar
Iron deposition in the pancreas can cause diabetes and to detect, this is done.
phenotyping of RBC When multiple transfusions are carried out, antibodies can form against donor blood therefore this is done prior to starting transfusion therapy phenotyping of RBC
When multiple transfusions are carried out, antibodies can form against donor blood therefore this is done prior to starting transfusion therapy
Hepatitis screen Children affected with Thalassemia are dependent on blood transfusion, therefore Hepatitis is an infection that is likely to transmit from blood. Therefore the child is first screened against Hepatitis. Hepatitis vaccination is carried out before starting transfusion. Hepatitis screen
Children affected with Thalassemia are dependent on blood transfusion, therefore Hepatitis is an infection that is likely to transmit from blood. Therefore the child is first screened against Hepatitis. Hepatitis vaccination is carried out before starting transfusion.
Folic acid level Blood level maybe done prior to starting transfusion and folic acid is also administered. Folic acid level
Blood level maybe done prior to starting transfusion and folic acid is also administered.
human leukocyte antigen (HLA) typing Stem cell transplantation is an emerging treatment method for thalassemia therefore to find a compatible donor, this is done. human leukocyte antigen (HLA) typing
Stem cell transplantation is an emerging treatment method for thalassemia therefore to find a compatible donor, this is done.
Full blood count To exclude any significant anemia prior to surgery (Splenectomy) Full blood count
To exclude any significant anemia prior to surgery (Splenectomy)
Coagulation studies To exclude any coagulopathy prior to surgery (Splenectomy) Coagulation studies
To exclude any coagulopathy prior to surgery (Splenectomy)
Renal function tests- Serum Creatinine, Blood urea nitrogen To exclude any renal dysfunction prior to anesthesia. Renal function tests- Serum Creatinine, Blood urea nitrogen
To exclude any renal dysfunction prior to anesthesia.
One tube osmotic fragility test This is used as a screening test. Test is positive when there's increased hemolysis in thalassemia due to increased target cells. One tube osmotic fragility test
This is used as a screening test. Test is positive when there's increased hemolysis in thalassemia due to increased target cells.
High performance liquid chromatography (HPLC) Most newborn screening programs worldwide use high-performance liquid chromatography (HPLC) as the first-line investigation to confirm the diagnosis High performance liquid chromatography (HPLC)
Most newborn screening programs worldwide use high-performance liquid chromatography (HPLC) as the first-line investigation to confirm the diagnosis
Echocardiogrpahy A staging system is present which takes the patient's symptoms, signs and echocardiogrpahic findings to stage thalessemia mainly to indicate the initiation of chelation therapy Echocardiogrpahy
A staging system is present which takes the patient's symptoms, signs and echocardiogrpahic findings to stage thalessemia mainly to indicate the initiation of chelation therapy
radionuclide cineangiogram A staging system is present which takes the patient's symptoms, signs and this test findings to stage thalessemia mainly to indicate the initiation of chelation therapy radionuclide cineangiogram
A staging system is present which takes the patient's symptoms, signs and this test findings to stage thalessemia mainly to indicate the initiation of chelation therapy
24-hour ECG A staging system is present which takes the patient's symptoms, signs and ECG findings to stage thalessemia mainly to indicate the initiation of chelation therapy 24-hour ECG
A staging system is present which takes the patient's symptoms, signs and ECG findings to stage thalessemia mainly to indicate the initiation of chelation therapy
Percutaneous liver biopsy Lucarelli classification, is used in patients who are about to undergo hematopoietic stem cell transplantation (HSCT) to assess hepatic iron content. Percutaneous liver biopsy
Lucarelli classification, is used in patients who are about to undergo hematopoietic stem cell transplantation (HSCT) to assess hepatic iron content.

Management - Supportive

Fact Explanation
Parent and patient education Parental education plays a major role in the management of thalassemia. This is a disease needs life long management with regular blood transfusions and regular follow up for complications is also important. sometimes psychiatric referral may be needed as it's a life long disease. Genetic counseling regarding the disease, and the screening of siblings is also needed Parent and patient education
Parental education plays a major role in the management of thalassemia. This is a disease needs life long management with regular blood transfusions and regular follow up for complications is also important. sometimes psychiatric referral may be needed as it's a life long disease. Genetic counseling regarding the disease, and the screening of siblings is also needed
Regular follow up Patient should be regularly followed up for blood transfusions and it's of much importance to follow up for complications of iron over load. Regular follow up
Patient should be regularly followed up for blood transfusions and it's of much importance to follow up for complications of iron over load.
Diet and activity A diet rich in folic acid, vitamin C is important as well as avoidance of iron rich food. Reduction in the level of activity is not needed unless the child is suffering from heart failure due to iron overload and cardiomyopathy in which restriction of activity is needed. Diet and activity
A diet rich in folic acid, vitamin C is important as well as avoidance of iron rich food. Reduction in the level of activity is not needed unless the child is suffering from heart failure due to iron overload and cardiomyopathy in which restriction of activity is needed.
Folic acid therapy Daily 5mg is given if the diet is poor. Folic acid therapy
Daily 5mg is given if the diet is poor.
Vitamin C therapy 200 mg/day is given and is thought to increase iron excretion Vitamin C therapy
200 mg/day is given and is thought to increase iron excretion
Vaccination Immunization against Hepatitis B and C prior to blood transfusion is needed. Also vaccination against Pneumococcal, Hemopilus, Meningococcal is needed prior to splenectomy. Vaccination
Immunization against Hepatitis B and C prior to blood transfusion is needed. Also vaccination against Pneumococcal, Hemopilus, Meningococcal is needed prior to splenectomy.
Screening Screening of parents and siblings is carried out when a child is diagnosed with thalassemia Screening
Screening of parents and siblings is carried out when a child is diagnosed with thalassemia
Prenatal diagnosis When two carriers are expecting a baby, prenatal diagnosis of the fetus for thalassemia is also available. Prenatal diagnosis
When two carriers are expecting a baby, prenatal diagnosis of the fetus for thalassemia is also available.

Management - Specific

Fact Explanation
Regular blood transfusion 2-3 units of fresh leukocyte depleted blood is given every 4-6 weeks in transfusion dependent anemia. Antipyretics, Antihistamines are adminisered before blood transfusion to prevent or decrease febrile reactions. Regular blood transfusion
2-3 units of fresh leukocyte depleted blood is given every 4-6 weeks in transfusion dependent anemia. Antipyretics, Antihistamines are adminisered before blood transfusion to prevent or decrease febrile reactions.
Endocrine therapy Insulin is given when there's diabetes mellitus, Calcium, Vitamin D and Bisphosphanates for osteoporosis. Iron deposition in the pituitary, and Deferoxamine therapy may cause growth retardation therefore growth hormone may be helpful. Endocrine therapy
Insulin is given when there's diabetes mellitus, Calcium, Vitamin D and Bisphosphanates for osteoporosis. Iron deposition in the pituitary, and Deferoxamine therapy may cause growth retardation therefore growth hormone may be helpful.
Iron chelation therapy In iron overloaded patients iron chelation therapy is initiated and
Deferoxamine is a parenteral drug that is used and Deferasirox, Deferiprone are oral iron chelators
Iron chelation therapy
In iron overloaded patients iron chelation therapy is initiated and
Deferoxamine is a parenteral drug that is used and Deferasirox, Deferiprone are oral iron chelators
Corticosteroids Local reactions may occur at Deferoxamine injection sites. Hydrocortisone may help to reduce the reaction. Corticosteroids
Local reactions may occur at Deferoxamine injection sites. Hydrocortisone may help to reduce the reaction.
Antibiotics Yersinia enterocolitica is one such organism that occurs in increased frequency in pateints on iron chelation therapy and they are treated with Trimethoprim-sulfamethoxazole (TMP/SMX) and gentamicin. Patients undergoing splenectomy need to receive prophylactic antibiotics as well Antibiotics
Yersinia enterocolitica is one such organism that occurs in increased frequency in pateints on iron chelation therapy and they are treated with Trimethoprim-sulfamethoxazole (TMP/SMX) and gentamicin. Patients undergoing splenectomy need to receive prophylactic antibiotics as well
Chemotherapeutic agents Chemotherapeutic agents such as Hydroxyurea have shown to reduce transfusion requirement in some patients Chemotherapeutic agents
Chemotherapeutic agents such as Hydroxyurea have shown to reduce transfusion requirement in some patients
Splenectomy The spleen is responsible for red blood cell destruction, therefore splenectomy may be considered if there's severe disease . Splenectomy
The spleen is responsible for red blood cell destruction, therefore splenectomy may be considered if there's severe disease .
Allogenic stem cell transplantation This is now the definitive treatment for Thalassemia which has a high success rate in well chelated, young patients without liver fibrosis or hepatomegaly. Allogenic stem cell transplantation
This is now the definitive treatment for Thalassemia which has a high success rate in well chelated, young patients without liver fibrosis or hepatomegaly.

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