Media Lab: Alpha Thalassemia
This drawing depicts which alpha chain genotype? Alpha thalassemia major (Hydrops fetalis) Alpha thalassemia intermedia (Hemoglobin H Disease) Normal Adult Silent Carrier
Alpha thalassemia intermedia (Hemoglobin H Disease) Feedback The genotype pictured, --/-α, is known as Alpha thalassemia intermedia or Hemoglobin H disease. When three gene loci of alpha chains are deleted (--/-α) or inactive, only 70-90% of Hemoglobin A is made. The excess beta chains that remain unpaired form the tetramers of Hemoglobin H.
In which disorder may a mild anemia be present even with an increased red blood cell (RBC) count and normal adult hemoglobin electrophoresis? Alpha thalassemia silent carrier Alpha thalassemia minor Alpha thalassemia intermedia Alpha thalassemia major
Alpha thalassemia minor Feedback Alpha thalassemia minor may show an increased RBC count and normal adult hemoglobin electrophoresis, even though the hemoglobin is decreased and anemia is present.
This image depicts a brilliant cresyl blue stained blood smear. Which arrow points to a cell that contains hemoglobin H bodies? A B C
B Feedback Hemoglobin H bodies precipitate just inside the RBC membrane and are usually lightly colored and evenly distributed around the cell. Normal hemoglobin, or that which has not yet precipitated, remains evenly distributed in the RBC giving it a smooth appearance. Brilliant cresyl blue that is used for this stain also precipitates remnants of RNA (similar to New methylene blue in the reticulocyte stain). These RNA remnants stain darker than Hemoglobin H bodies and are few in number.
Which of the following constitutes the alpha hemoglobin chain coding? Two gene loci; one each on chromosome 11 Four gene loci; two each on chromosome 11 Two gene loci; one each on chromosome 16 Four gene loci; two each on chromosome 16
Four gene loci; two each on chromosome 16 Feedback Humans need four gene loci that code for the alpha hemoglobin chain, in order to make their full component of normal hemoglobins. Two alpha chain gene loci are found on each chromosome 16.
What characteristics are often associated with alpha thalassemia intermedia? Nothing abnormal Polycythemia, hepatomegaly, Anemia, splenomegaly
Anemia, splenomegaly Feedback Infants born with alpha thalassemia intermedia appear normal at birth but often develop anemia and splenomegaly by the end of their first year. Hepatomegaly is not a common finding.
Which hemoglobin(s) can be decreased in alpha thalassemia? (Choose all that apply) More than one answer is correct. Hb A Hb A2 Hb F Hb H
Hb A Hb A2 Hb F Feedback Because alpha chains are needed to form all normal hemoglobins, and alpha thalassemia is the decrease in production of alpha chains, all normal hemoglobins can be decreased in alpha thalassemia: A, A2, and F.
Which abnormal hemoglobins may be formed in alpha thalassemia? (Choose all that apply) More than one answer is correct. Hb Bart's Hb Lepore Hb E Hb H Hb O
Hb Bart's Hb H Feedback In alpha thalassemia intermedia or Hemoglobin H disease, insufficient alpha chains are produced. The remaining globin chains often form tetramers. In neonates the gamma chain is present in high amounts, forming tetramers known as Bart's hemoglobin. As gamma chain production decreases, beta chain production increases. Adults form beta chain tetramers (Hemoglobin H).
In which disorder do neonates demonstrate the presence of Bart's hemoglobin that changes to beta chain tetramers in adults? Alpha thalassemia major Alpha thalassemia minor Hemoglobin H disease Hydrops fetalis
Hemoglobin H disease Feedback When insufficient alpha chains are produced, the remaining globin chains often form tetramers. This condition is seen in alpha thalassemia intermedia or Hemoglobin H disease. In neonates the gamma chain is present in high amounts, forming tetramers known as Bart's hemoglobin. As gamma chain production decreases, beta chain production increases. Adults form beta chain tetramers (Hemoglobin H). Although hemoglobin Bart's is produced in Hydrops Fetalis, these patients do not survive and therefore would not go on to produce hemoglobin H.
The gene loci for the alpha globin chains are adjacent to the locus for which other globin chain? Beta Delta Epsilon Zeta
Zeta Feedback The order of globin gene loci on chromosome 16 is Zeta, Alpha 2, and Alpha 1.
Mark all genotypes that cause alpha thalassemia minor. More than one answer is correct. -α/αα -α/-α --/αα --/-α --/--
-α/-α --/αα Feedback Deletion of two out of four alpha chain gene loci results in alpha thalassemia minor. The deletions may be homozygous or heterozygous: In the homozygous state (-α/-α), both parents contribute one missing gene locus. In the heterozygous state (--/αα), one parent contributes a normal gene while the other one a gene with both alpha chain gene loci deleted.
On this alkaline electrophoresis gel, which patient most likely has an alpha thalassemia syndrome? https://docs.google.com/document/d/1q89iU3gNxcgB4-yrPA0Tz-dQlhL3OaPCKznuWTXtYes/edit?usp=sharing 1 2 3 4
3 Feedback Lane six in this alkaline electrophoresis demonstrates the typical control pattern of hemoglobins C, S, and A from left to right; and Lane five is the hemoglobin F, A control. The patient lanes show the following patterns from left to right: Lane 1- normal (nearly undetectable) amounts of hemoglobin A2, and normal hemoglobin A Lane 2- equal amounts of hemoglobin C, and hemoglobin A Lane 3- decreased amount of hemoglobin A, and a clearly visible band of hemoglobin H Lane 4- a visible band of hemoglobin A2, and near equal amounts of hemoglobin S, and hemoglobin A
A patient with alpha thalassemia, who is African American, most likely has which form of the disorder? Major Heterozygous minor Homozygous minor Intermedia
Homozygous minor Feedback The homozygous form of alpha thalassemia minor can be seen in African Americans. The heterozygous form of alpha thalassemia minor and other alpha thalassemias is more often seen in persons from Southeast Asia and the Mediterranean.
Which set of chemistry results would most likely occur during hemolytic crisis in alpha thalassemia intermedia? Please select the single best answer Decreased lactate dehydrogenase (LD)and bilirubin, and increased haptoglobin Increased LD and bilirubin,and decreased haptoglobin Increased LD and bilirubin, and normal haptoglobin Normal LD and bilirubin, and decreased haptoglobin
Increased LD and bilirubin, and normal haptoglobin Feedback Alpha thalassemia is a hemolytic anemia. In most hemolytic anemias the LD and bilirubin are increased while the haptoglobin is decreased. However, because haptoglobin binds to the alpha chain portion of hemoglobin, it usually remains at normal levels due to the absence of alpha chains in the destroyed cells.
What RBC morphology on a Wright-stained smear may indicate the presence of an unstable hemoglobin. Acanthocytes Codocytes Schistocytes Xerocytes
Schistocytes Feedback Though not diagnostic for alpha thalassemia, schistocytes (fragmented RBCs) indicate that there is one of several forms of red blood cell destruction occurring. When unstable hemoglobin is formed, such as Hemoglobin H in alpha thalassemia intermedia, macrophages may remove the precipitated tetramers out of the cell, leaving it appearing "bitten."
Which of the following alpha thalassemia syndromes has the genotype -α/αα ? Silent carrier Alpha thalassemia minor Alpha thalassemia intermedia Alpha thalassemia major
Silent carrier Feedback The genotype -α/αα is known as silent carrier. Individuals who are silent carriers show no clinical disease and demonstrate normal results during routine laboratory testing (Enough alpha chains can be made with only three functioning gene loci). This form of alpha thalassemia is usually discovered upon family studies.
What are the usual results of the mean corpuscular volume (MCV) and the red cell distribution width (RDW) in alpha thalassemia? Both within normal range The MCV is decreased but the RDW is usually increased The MCV is increased but the RDW is normal Both the MCV and RDW are decreased.
The MCV is decreased but the RDW is usually increased The thalassemias are classified as microcytic anemias, thus these patients have decreased MCV values. The red blood cell distribution width (RDW) increases as the severity of alpha thalassemia increases because of changing MCV as the bone marrow produces smaller cells. In addition, if Hemoglobin H bodies are present, they result in the formation of schistocytes (RBC fragments) that can have an effect on the MCV and RDW. Even if the patient is not anemic, someone with thalassemia typically has at least an MCV below range. The MCV is never increased in thalassemia since there is an insufficient amount of globin produced and the cells are smaller than normal. It is rare to have a decreased RDW in any condition, and particularly not thalassemia.
The life span of RBCs containing Hemoglobin H is typically: decreased increased unchanged
decreased Feedback The life span of an RBC containing Hemoglobin H bodies is decreased because the RBC membrane is compromised when macrophages attempt to remove this unstable hemoglobin, which is precipitated just inside the membrane.
The bone marrow in alpha thalassemia usually demonstrates: aplasia hypoplasia normoplasia hyperplasia
hyperplasia Feedback The bone marrow in alpha thalassemia often demonstrates erythroid hyperplasia, as it tries to compensate for the anemia that is present.
Hemoglobin H bodies can directly alter the: function of the spleen bone marrow micro environment rate of hemoglobin production integrity of the RBC membrane
integrity of the RBC membrane Feedback When unstable hemoglobin is formed, such as Hemoglobin H in alpha thalassemia intermedia, it precipitates close to the RBC membrane. The integrity of the membrane is compromised when macrophages remove the precipitated tetramers out of the cell. These cells can appear as if "bites" were taken out of them or as fragmented cells (schistocytes).
