Name two diseases associated with Heinz bodies.
-Thalassemia and glucose-6-phosphate dehydrogenase deficiency
What type of red blood cell morphology would you see in the peripheral blood that is associated with Heinz bodies?
Bite cells; the spleen bites off the precipitated hemoglobin in the cells
What is the role of the mean corpuscular volume in an anemia workup?
A mean corpuscular volume < 80 fL is a microcytic anemia; a volume > 100 fL is a macrocytic anemia; a volume between those values is a normocytic anemia
What are three etiologies of iron-deficiency anemia?
Loss (chronic bleeding), malnutrition or poor absorption, and increased demand (such as in pregnancy)
What biochemical pathway is interrupted in iron deficiency anemia?
The formation of heme (which requires iron)
You see a patient with tongue inflammation and atrophy, dysphagia for solids, and a hemoglobin of 9 g/dL; what is the cause of his anemia?
This patient has Plummer-Vinson syndrome, the triad of esophageal webs, atrophic glossitis, and iron deficiency anemia
What disease, common in Asia and Africa, is caused by deletions of the hemoglobin chain gene?
-thalassemia; gene deletions result in decreased globin synthesis
What would you see on hemoglobin electrophoresis in a fetus with deletions of all four globin genes?
Hemoglobin Barts (γ4); this is a lethal condition and will result in hydrops fetalis
A fetus undergoes amniocentesis and is found to have deletions of all four globin genes; what is the likely outcome?
Hydrops fetalis; deletion of four genes is incompatible with life
What condition would you expect to see in a patient with a deletion of three of the four globin genes?
Symptomatic microcytic anemia due to -thalassemia; known as hemoglobin H disease (4)
A mother is concerned that her child has deletions of two globin genes; what symptoms will likely manifest?
Deletion of one or two globin genes is not associated with symptomatic anemia
What disease, seen in people that live in the Mediterranean region, is caused by point mutations in hemoglobin chain genes?
-Thalassemia; typically these mutations are at splicing sites and in the promoter regions
What type of mutation is present in a patient with -thalassemia minor?
There is a mutation in one gene (heterozygote), causing underproduction of globin; the mutation is often in a promoter or splice site
What symptoms and laboratory findings are consistent with -thalassemia minor?
This condition is asymptomatic, and diagnosed by an hemoglobin A2 > 3.5% on electrophoresis
What treatment is indicated in a patient with -thalassemia major?
Because both genes are mutated, there is no chain production and the patient requires many blood transfusions
What is a long-term adverse effect of the treatment of -thalassemia major?
Iron overload (secondary hemochromotosis) due to repeated blood transfusions
What x-ray finding should raise your suspicion of -thalassemia major?
Bone marrow expansion, which can be seen as increased marrow space, bone deformities (chipmunk facies), and a crew-cut appearance of the skull x-ray
What should you see on hemoglobin electrophoresis in a patient with -thalassemia (major and minor) that, as in infants, increases the blood's affinity for oxygen?
Increased fetal hemoglobin (2; γ2)
What disease do you expect to see in a child born to a father homozygous for hemoglobin S and a mother with -thalassemia major?
This child will be a hemoglobin S/-thalassemia heterozygote, which presents with mild or moderate sickle cell disease based on chain production
Lead poisoning disrupts which two enzymes involved in the formation of hemoglobin?
Lead blocks ferrochelatase and ALA dehydratase, which decreases the synthesis of heme
What is the cause of basophilic stippling associated with lead poisoning?
Lead disrupts the degradation of RNA, which builds up and stains with basic dyes
What is the cause of hereditary sideroblastic anemia?
A mutation in the δ-aminolevulinic acid gene
What is the inheritance pattern associated with a mutation in the δ-aminolevulinic acid gene?
This mutation, which causes a hereditary sideroblastic anemia, is found on the X chromosome
What is the treatment for sideroblastic anemia due to a mutation in δ-ALA synthase?
Pyridoxine (vitamin B6)
Name two reversible causes of sideroblastic anemia
Alcohol use and lead poisoning
A patient has an elevated serum iron and ferritin, and a normal total iron-binding capacity; what diagnosis should you suspect if a bone marrow aspirate shows blast forms of erythrocytes that have a dark ring around the nucleus?
Sideroblastic anemia; the aspirate describes the iron-laden mitochondria that create the appearance of a ringed sideroblast
Why is the mean corpuscular volume increased in megaloblastic macrocytic anemia?
There is a defect in DNA synthesis: the nucleus takes longer to mature than the cytosol and thus there is excess cytoplasm, creating a megaloblast; this is caused by B12 and folate deficiency
A patient has anemia with a mean corpuscular volume of 110 fL and glossitis and on the peripheral smear you note hypersegmented neutrophils; what are the two possible causes of this condition?
B12 or folate deficiency; both present with these features
What laboratory test (other than a vitamin level) will distinguish between B12 and folate deficiency as a cause of megaloblastic anemia?
Methylmalonic acid is elevated in B12 deficiency but normal in folate deficiency; homocysteine is elevated in both deficiencies
What is the homocysteine level in patients with B12 and folate deficiency?
Both B12 and folate deficiencies have elevated homocysteine levels