Difference between revisions of "Thalassemia"

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==Background==
 
==Background==
*A group of hereditary disorders resulting in microcytic, hypochromic, hemolytic anemia
+
*A group of hereditary disorders resulting in microcytic, hypochromic, hemolytic [[anemia]]
 
*Most common in Mediterranean, Middle Eastern, African and Southeast Asian population
 
*Most common in Mediterranean, Middle Eastern, African and Southeast Asian population
  
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**β-globin gene mutations cause β-thalassemia; ɑ-globin mutations cause ɑ-thalassema
 
**β-globin gene mutations cause β-thalassemia; ɑ-globin mutations cause ɑ-thalassema
  
ɑ-Thalassemia Carrier and Trait
+
===ɑ-Thalassemia Carrier and Trait===
*no clinical symptoms or physical findings
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*No clinical symptoms or physical findings
*microcytic RBCs and normal Hb level
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*Microcytic RBCs and normal Hb level
  
Hemoglobin H Disease (HbH disease)
+
===Hemoglobin H Disease (HbH disease)===
*one ɑ-globin chain gene is still functional
+
*One ɑ-globin chain gene is still functional
*typically presents in neonatal period with severe hypochromic anemia
+
*Typically presents in neonatal period with severe hypochromic [[anemia]]
*hypochromic, microcytic anemia with jaundice and hepatosplenomegaly
+
*Hypochromic, microcytic anemia with [[jaundice]] and [[hepatomegaly|hepatosplenomegaly]]
*may not require regular transfusions
+
*May not require regular [[pRBCs|transfusions]]
*tranfusions may be necessary in setting of increased oxidative stress or infection which may precipitate hemolysis
+
*[[pRBCs|Transfusions]] may be necessary in setting of increased oxidative stress or infection which may precipitate [[hemolytic anemia|hemolysis]]
 +
*Note that alpha thalassemia major (Hb Bart) results in [[hydrops fetalis]], and thus is not an adult disease process
  
β-Thalassemia Minor (β-Thalassemia Trait)
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===β-Thalassemia Minor (β-Thalassemia Trait)===
*heterozygous for β-globin mutation
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*Heterozygous for β-globin mutation
*mild microcytic anemia
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*Mild microcytic [[anemia]]
*splenomegaly uncommon
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*Splenomegaly uncommon
*microcytosis, hypochromia, basophilic stippling on blood smear
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*Microcytosis, hypochromia, basophilic stippling on blood smear
*no clinical symptoms
+
*Co clinical symptoms
  
β-Thalassemia Major (Cooley Anemia)
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===β-Thalassemia Major (Cooley Anemia)===
*both β-globin genes defective; β-globin chain production severely impaired
+
*Both β-globin genes defective; β-globin chain production severely impaired
*typically presents >6mos of life (HbF production replaced with β-globin to form HbA)
+
*Typically presents >6mos of life (HbF production replaced with β-globin to form HbA)
*hepatosplenomegaly, jaundice, expansion of erythroid marrow causing bone changes and osteoporosis, susceptible to infection
+
*[[hepatomegaly|Hepatosplenomegaly]], [[jaundice]], expansion of erythroid marrow causing bone changes and osteoporosis, susceptible to [[osteomyelitis|infection]]
*severe anemia requiring regular and lifelong blood transfusions
+
*Severe [[anemia]] requiring regular and lifelong blood [[pRBCs|transfusions]]
**iron overload secondary to frequent transfusions is etiology of most of morbidity and mortality
+
**[[hemochromatosis|Iron overload]] secondary to frequent transfusions is etiology of most of morbidity and mortality
*low MCV with microcytic and hypochromic RBC
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*Low MCV with microcytic and hypochromic RBC
  
Sickle Cell-β-Thalassemia Disease
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===Sickle Cell-β-Thalassemia Disease===
 
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*Gene for sickle Hb is inherited from one parent and gene for β-thalassemia is inherited from the other parent
ɑ
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*1 per 1600 African American births
β
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*Severity depends on type of β-thalassemia gene inherited
 +
**80-90% inherit β-thalassemia gene that has some normal β-chain production; these patients have mild hemolytic anemia with near-normal Hb levels, few crises
 +
**10-20% inherit β-thalassemia gene that produces no-chains; these patients have severe [[hemolytic anemia]] and [[vaso-occlusive crisis|vaso-occlusive symptoms]]
  
 
==Differential Diagnosis==
 
==Differential Diagnosis==
 +
===[[Anemia]]===
 +
====RBC Loss====
 +
*[[Hemorrhage]]
 +
====RBC consumption (Destruction/hemolytic)====
 +
*Hereditary
 +
**[[Sickle cell disease]]
 +
**[[Glucose-6-phosphate deficiency]]
 +
*Acquired
 +
*[[Microangiopathic Hemolytic Anemia (MAHA)]]
 +
*[[Autoimmune hemolytic anemia]]
 +
====Impaired Production (Hypochromic/microcytic)====
 +
*Iron deficiency
 +
*Anemia of chronic disease
 +
*[[Thalassemia]]
 +
*Sideroblastic anemia
 +
====Aplastic/myelodysplastic (normocytic)====
 +
*Marrow failure
 +
*Chemicals (e.g. [[ETOH]])
 +
*Radiation
 +
*Infection ([[HIV]], [[parvovirus B19|parvo]])
 +
====Megaloblastic (macrocytic)====
 +
*Vitamin B12/folate deficiency
 +
*Drugs (chemo)
 +
*[[HIV]]
  
 
==Evaluation==
 
==Evaluation==
 +
*CBC
 +
*CMP
 +
*Blood smear
 +
*Reticulocyte count
 +
*LDH
 +
*Haptoglobin
  
 
==Management==
 
==Management==
 +
*Identify and discontinue precipitating agent
 +
*Supportive care
 +
*[[pRBCs|Blood transfusions]] for severe anemia
  
 
==Disposition==
 
==Disposition==
  
 
==See Also==
 
==See Also==
 +
*[[Anemia]]
  
 
==External Links==
 
==External Links==
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==References==
 
==References==
 
<references/>
 
<references/>
 +
*Tintinalli's Emergency Medicine 7th Edition, pg1486-7
 +
 +
[[Category: Heme/Onc]]

Latest revision as of 18:47, 1 October 2019

Background

  • A group of hereditary disorders resulting in microcytic, hypochromic, hemolytic anemia
  • Most common in Mediterranean, Middle Eastern, African and Southeast Asian population

Clinical Features

  • Categorized depending on globin chain affected or the abnormal Hb produced
    • β-globin gene mutations cause β-thalassemia; ɑ-globin mutations cause ɑ-thalassema

ɑ-Thalassemia Carrier and Trait

  • No clinical symptoms or physical findings
  • Microcytic RBCs and normal Hb level

Hemoglobin H Disease (HbH disease)

  • One ɑ-globin chain gene is still functional
  • Typically presents in neonatal period with severe hypochromic anemia
  • Hypochromic, microcytic anemia with jaundice and hepatosplenomegaly
  • May not require regular transfusions
  • Transfusions may be necessary in setting of increased oxidative stress or infection which may precipitate hemolysis
  • Note that alpha thalassemia major (Hb Bart) results in hydrops fetalis, and thus is not an adult disease process

β-Thalassemia Minor (β-Thalassemia Trait)

  • Heterozygous for β-globin mutation
  • Mild microcytic anemia
  • Splenomegaly uncommon
  • Microcytosis, hypochromia, basophilic stippling on blood smear
  • Co clinical symptoms

β-Thalassemia Major (Cooley Anemia)

  • Both β-globin genes defective; β-globin chain production severely impaired
  • Typically presents >6mos of life (HbF production replaced with β-globin to form HbA)
  • Hepatosplenomegaly, jaundice, expansion of erythroid marrow causing bone changes and osteoporosis, susceptible to infection
  • Severe anemia requiring regular and lifelong blood transfusions
    • Iron overload secondary to frequent transfusions is etiology of most of morbidity and mortality
  • Low MCV with microcytic and hypochromic RBC

Sickle Cell-β-Thalassemia Disease

  • Gene for sickle Hb is inherited from one parent and gene for β-thalassemia is inherited from the other parent
  • 1 per 1600 African American births
  • Severity depends on type of β-thalassemia gene inherited
    • 80-90% inherit β-thalassemia gene that has some normal β-chain production; these patients have mild hemolytic anemia with near-normal Hb levels, few crises
    • 10-20% inherit β-thalassemia gene that produces no-chains; these patients have severe hemolytic anemia and vaso-occlusive symptoms

Differential Diagnosis

Anemia

RBC Loss

RBC consumption (Destruction/hemolytic)

Impaired Production (Hypochromic/microcytic)

  • Iron deficiency
  • Anemia of chronic disease
  • Thalassemia
  • Sideroblastic anemia

Aplastic/myelodysplastic (normocytic)

  • Marrow failure
  • Chemicals (e.g. ETOH)
  • Radiation
  • Infection (HIV, parvo)

Megaloblastic (macrocytic)

  • Vitamin B12/folate deficiency
  • Drugs (chemo)
  • HIV

Evaluation

  • CBC
  • CMP
  • Blood smear
  • Reticulocyte count
  • LDH
  • Haptoglobin

Management

  • Identify and discontinue precipitating agent
  • Supportive care
  • Blood transfusions for severe anemia

Disposition

See Also

External Links

References

  • Tintinalli's Emergency Medicine 7th Edition, pg1486-7