Term
| A group of hereditary disorders in which there is a defect in the rate of synthesis of one or more of the globin chains of hemoglobin |
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Definition
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Term
| What are the two broad classifications of hemoglobinopathies? |
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Definition
| Those which result from a structural alteration in the globin chain, like sickle cell disease; and those which are the result of defects in the rate of synthesis of the globin chain- the thalassemias. |
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Term
| Who discovered thalassemias, and when? |
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Definition
| Dr. Thomas Cooley, in 1925 |
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Term
| Where did the name thalassemia come from? |
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Definition
| the greek word for "the sea", because the first cases found were in people of Mediterranean background. |
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Term
| Is thalassemia rare, or common? |
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Definition
| It is one of the world's most common genetic disorders. |
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Term
| Thalassemia produces hematologic abnormalities similar to those seen in what other type of anemia? |
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Definition
| Severe iron deficiency anemia. |
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Term
| The globin genes are located on what two chromosomes? |
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Definition
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Term
| What is the globin chain structure of Hgb F? |
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Definition
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Term
| What is the globin chain structure of Hgb A? |
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Definition
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Term
| What is the globin chain structure of Hgb A2? |
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Definition
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Term
| What two hemoglobins are normally found in the newborn, and what percent? |
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Definition
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Term
| What three Hgb's are normally found in the adult, and what percents? |
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Definition
| Hgb A- 97% Hgb A2- 2% Hgb F- 1% |
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Term
| When the amount of normal hemoglobin produced is decreased, what is the effect on the red cells? |
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Definition
| microcytic, hypochromic anemia. |
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Term
| What abnormal hemoglobins are formed in alpha thalassemia? |
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Definition
| Hgb Barts- G4, and Hgb H- B4 |
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Term
| What abnormal hemoglobins are formed in beta thalassemia? |
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Definition
| A2 precipitates formed from excess alpha chains- these aren't actually hemoglobins they are just abnormal precipitated chains. |
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Term
| In beta thalassemia, what is the cause of the chronic hemolytic process? |
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Definition
| A2 precipitates cause membrane damage; damaged cells are destroyed by macrophages and/or splenic pitting. |
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Term
| What are the two main variants of thalassemias? |
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Definition
| Alpha thalassemia and Beta thalassemia |
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Term
| Constant spring, hemoglobin lepore, and hereditary persistance of fetal hemoglobin are all what? |
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Definition
| Minor variants of thalassemia |
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Term
| In beta thalassemia, synthesis of which globin chain is absent or diminished? |
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Definition
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Term
| Does beta thalassemia affect newborns? |
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Definition
| No because newborns aren't making beta chains yet. |
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Term
| What thalassemia is characterized by elevated levels of Hgb A2 and F? |
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Definition
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Term
| How many genotypic variants are there of Beta thalassemia? |
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Definition
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Term
| How many different mutations are included in the B+ variant? |
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Definition
| Over 120 different mutations; extreme variability in amount of beta chain produced. |
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Term
| What are the four classifications of Beta thalassemia according to phenotype? |
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Definition
| Thalassemia major, Thalassemia intermedia, Thalassemia minor and Silent carrier. |
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Term
| Cooley's anemia is another name for what? |
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Definition
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Term
| Thalassemia major can be caused by what three genotypes? |
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Definition
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Term
| What disorder is characterized by bone changes secondary to extremely hyperplastic bone marrow? |
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Definition
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Term
| What microcytic anemia is usually diagnosed in the first year of life, with symptoms like failure to thrive, diarrhea, fever, hepatosplenomegaly and skeletal deformities? |
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Definition
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Term
| Why do Thalassemia major patients develop hemochromatosis? |
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Definition
| Hemochromatosis is iron overload, they develop it because of repeated blood transfusions. |
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Term
| Hemoglobin electrophoresis shows that the majority of hemoglobin is F, A2 is increased, and A is decreased or absent. What thalassemia is this? |
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Definition
| Beta thalassemia- Thalassemia major |
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Term
| What is the prognosis for Thalassemia major patients? |
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Definition
| Death in second or third decade from cardiac siderosis- iron overload |
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Term
| In thalassemia major, the spleen is sometimes removed- why? |
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Definition
| To decrease hemolysis and increase red cell survival. |
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Term
| What inclusions are found in thalassemia major? |
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Definition
| basophilic stippling, heinz bodies. |
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Term
| Are Howell Jolly bodies associated with Thalassemia? |
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Definition
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Term
| What genotypes could cause Thalassemia intermedia? |
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Definition
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Term
| What is the Hgb concentration in thalassemia intermedia? |
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Definition
| Hgb is 7 g/dL or greater. |
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Term
| What is the percentage of hemoglobin F in thalassemia intermedia? |
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Definition
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Term
| What poikilocytes would you see in thalassemia intermedia? |
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Definition
| target cells, basophilic stippling, microcytic hypochromic RBC's |
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Term
| What is the level of hgb A2 in thalassemia intermedia? |
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Definition
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Term
| What genotypes could cause thalassemia minor? |
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Definition
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Term
| How many abnormal beta genes are present in thalassemia intermedia? |
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Definition
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Term
| How many abnormal beta genes are present in thalassemia major? |
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Definition
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Term
| How many abnormal beta genes are present in thalassemia minor? |
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Definition
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Term
| How many abnormal beta genes are present in silent carrier of beta thalassemia? |
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Definition
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Term
| What is the percent of hgb A2 in thalassemia minor? |
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Definition
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Term
| What is the percent of hemoglobin F in thalassemia minor? |
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Definition
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Term
| What hematologic value differentiates thalassemia minor from Fe deficiency? |
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Definition
| Red cell count is normal to slightly increased in thal minor; in Fe deficiency it's decreased. |
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Term
| How is the Mentzer index calculated? |
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Definition
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Term
| What is the Mentzer index used for? |
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Definition
| To differentiate between Thal minor and Fe deficiency. |
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Term
| What is indicated by a Mentzer index of less than 13? |
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Definition
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Term
| What is indicated by a Mentzer index of greater than 13? |
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Definition
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Term
| What is the genotype of a beta thalassemia silent carrier? |
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Definition
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Term
| What happens in delta-beta thalassemia? |
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Definition
| Lack of db genes; g genes left intact and overcompensate. |
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Term
| Homozygous delta-beta thalassemia is clinically similar to what other thalassemia? |
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Definition
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Term
| What hemoglobins are present in homozygous delta-beta thalassemia? |
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Definition
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Term
| If a patient can only make hgb F, what is the diagnosis? |
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Definition
homozygous delta-beta thalassemia
or
hereditary persistance of fetal hemoglobin |
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Term
| heterozygous delta-beta thalassemia phenotypically presents as what? |
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Definition
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Term
| What thalassemia has 5-20% hgb F, 90% hgb A, and normal A2? |
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Definition
| Heterozygous delta-beta thalassemia |
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Term
| Which hemoglobinopathy is thought to be a product of delta-beta fusion genes which arise by unequal crossing over between delta and beta globin loci during meiosis? |
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Definition
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Term
| Hgb Lepore migrates to the same position as what other hemoglobin at pH 8.4? |
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Definition
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Term
| What hemoglobins are present in homozygous hemoglobin lepore, and what percentages? |
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Definition
| 20% Hgb Lepore, 80% Hgb F |
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Term
| In heterozygous hemoglobin lepore, what percent of the total hemoglobin is hemoglobin lepore? |
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Definition
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Term
| What is the name of this form of delta-beta thalassemia in which gamma genes are not switched off and are able to fully compensate for lack of delta and beta chain production? |
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Definition
| HPFH- hereditary persistance of fetal hemoglobin |
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Term
| In HPFH, do excess alpha chains accumulate and precipitate? |
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Definition
| No, because gamma chain production is increased. |
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Term
| In homozygous HPFH, what hemoglobins are made? |
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Definition
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Term
| Do patients with homozygous HPFH have severe anemia? |
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Definition
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Term
| When does alpha thalassemia manifest itself? |
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Definition
| At birth. Hgb F is not made. |
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Term
| Is alpha thalassemia usually caused by deletions or by point mutations? |
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Definition
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Term
| What thalassemia is characterized by globin tetramers? |
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Definition
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Term
| How many alpha genes are located on each chromosome 16? |
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Definition
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Term
| How many alpha genes does a normal person have? |
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Definition
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Term
| Thalassemia with 100% Hgb F; mild to moderate anemia. |
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Definition
| Homozygous delta-beta thallasemia. |
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Term
| Thalassemia with 100% Hgb F; little or no anemia. |
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Definition
| Hereditary persistance of fetal hemoglobin- HPFH |
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Term
| What two thalassemias have 100% Hgb F? |
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Definition
| HPFH and Homozygous delta-beta thalassemia |
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Term
| What is the genotype of an alpha thalassemia silent carrier? |
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Definition
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Term
| Does the alpha thalassemia silent carrier produce Hgb Barts? How much and when? |
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Definition
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Term
| Hydrops Fetalis is a fatal type of what thalassemia? |
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Definition
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Term
| The genotype --/-- is associated with what? |
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Definition
| Hydrops Fetalis/ fatal form of alpha thalassemia. |
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Term
| What causes Hgb H disease? |
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Definition
| Hgb H disease is a form of alpha thalassemia with 3 gene deletions or 3 affected genes. |
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Term
| How many gene deletions does a-thal minor have? |
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Definition
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Term
| What inclusions are present in a-thal minor? |
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Definition
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Term
| What is the most difficult type of thalassemia to identify clinically and genetically? |
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Definition
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Term
| Why is a-thal minor usually diagnosed at birth? |
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Definition
| it is one of very few causes of microcytosis at birth; also Hgb Barts is present until about 3 months. Hgb H inclusions may be present. |
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Term
| What is the O2 affinity of Hgb H compared to Hgb A? |
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Definition
| The O2 affinity of Hgb H is 10x that of Hgb A. |
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Term
| What stain is used to visualize Hgb H inclusions and heinz bodies? |
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Definition
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Term
| What is the fastest migrating hemoglobin on cellulose acetate at pH 8.4? |
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Definition
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Term
| Accelerate Fast Slow Crawls. What is this referring to? |
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Definition
| The order of hemoglobins migrating in electrophoresis. |
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Term
| In hemoglobin electrophoresis, are the hemoglobins going toward the positive or negative? |
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Definition
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Term
| A patient has a microcytic hypochromic anemia. Serum iron is decreased; TIBC is increased; % saturation is decreased. Anisocytosis and poikilocytosis, and target cells, are present on peripheral smear. Diagnosis? |
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Definition
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Term
| A patient has microcytic hypochromic anemia. Serum iron is decreased, TIBC is slightly decreased, % saturation is decreased. No anisocytosis or poikilocytosis is noted on the peripheral smear. Diagnosis? |
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Definition
| Anemia of chronic disease. |
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Term
| A patient has microcytic hypochromic anemia. Serum Fe is increased; serum ferritin is increased, ringed sideroblasts present in BM; % saturation is increased. The smear shows anisocytosis and poikilocytosis, target cells, and basophilic stippling. Diagnosis? |
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Definition
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Term
| Lead poisoning is associated with what anemia? |
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Definition
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