Flashcards in Pathology of Anemia II Deck (38)
What is thalassemia?
Group of genetic disorders characterized by the lack, or decreased synthesis, of either alpha or beta-globin chains of hemoglobin A
What is alpha thalassemia?
– alpha-thalassemia - globin chain synthesis is reduced
What is beta thalassemia?
– beta-thalassemia - -globin chain synthesis is absent or reduced
What are some consequences of thalassemia?
– low intracellular hemoglobin (hypochromia)
– relative excess of other chain
What are the 4 types of alpha thalassemia?
- Silent carrier -a/aa
- α-thalassemia trait
-a/-a (black African)
- HbH disease --/-a
- ￼￼￼￼￼￼Hydropsfetalis --/--
It refers to lack of ß-globin expression
It refers to decreased ß-globin expression
How does ß-thalassemia cause anemia?
– reduced synthesis of -globin leading to inadequate HbA formation
– hemolytic component of the disease due to relative excess of -globin chains
Clinical term to describe severe disease, reliance on transfusions
Clinical term to describe patients with asymptomatic, mild or absent anemia, some RBC abnormalities
What can be seen in the skull of ß-thalassemia patients?
Crew cut - expansion of marrow in the skull trying to
produce RBCs in beta thalassemia major
What do target cells in the smear indicate?
What is the only acquired defect in the RBC membrane?
Paroxysmal Nocturnal Hemoglobinuria
What is the change in Paroxysmal Nocturnal Hemoglobinuria?
Stem cell disorder that results from a mutation in the phosphatidylinositol glycan A (PIGA) gene which results in a deficiency of the GPI anchor
What are some important GPI proteins and what are they functions?
– CD55 (decay-accelerating factor)
– CD59 (membrane inhibitor of reactive lysis)
– C8 binding protein
These proteins are involved in inactivating or the complement pathway - leads to unchecked activation and RBC destruction
How can mechanical trauma cause anemia?
- Anemia due to prosthetic cardiac valves that destroy RBCs
- Narrowing of small vessels and fibrin deposition (microangiopathic hemolytic anemia)
What is seen on smear with mechanical trauma?
What are often causes of iron deficiency anemia?
- Some disorders result in malabsorption of iron (sprue, gastrectomy)
- Adequate diet under usual circumstances may not meet demand for iron during pregnancy and infancy
- Most important cause of iron deficiency in the Western world is chronic blood loss
What happens to total iron binding capacity (TIBC) in iron deficiency anemia?
What happens to the size of cells in iron deficiency anemia?
They become small - microcytic
What is seen on smear with iron deficiency anemia?
Central pallor spreads to almost the entire cell
What is megaloblastic anemia?
Disturbances of proliferation and maturation of erythroblasts due to defective DNA synthesis
What are the 2 types of megaloblastic anemia?
- Vitamin B12
What are the functions of vitamin B12 and folate?
Both B12 and folate are coenzymes in the DNA biosynthetic pathway
What happens to the size of cells in megaloblastic anemia?
Enlargement of proliferating cells, particularly in erythroid precursors, is seen - macrocytic
What are enlarged RBC precursors and enlarged RBCs called?
– enlarged red cell precursors are called megaloblasts
– enlarged red cells are called macrocytes or macro-ovalocytes
Why is there enlargement in megaloblastic anemia?
Impairment of DNA synthesis underlies enlargement. Cellular nuclei are immature and cytoplasm is fully mature: nuclear- cytoplasmic asynchrony.
What are some causes of vitamin B12 deficiency?
– Inadequate diet (vegetarians at increased risk)
– Increased requirements
– Impaired absorption (Intrinsic Factor deficiency)
What is pernicious anemia?
“Pernicious anemia” applies to vitamin B12 deficiency secondary to atrophic gastritis with failure of production of intrinsic factor (IF)
What are the clinical findings with vitamin B12 deficiency?
Clinical findings found mainly in alimentary tract, blood, bone marrow, and in CNS
What can be seen on a smear in megaloblastic anemia?
What are the clinical findings of folate deficiency?
Similar to vitamin B12 megaloblastic anemia, but there are no CNS effects
How does treatment of vitamin B12 deficiency with folate work out?
Prompt response - folic acid will improve B12 deficiency
as well but does NOT treat the CNS abnormalities
What is anemia of chronic disease?
Caused by high levels of plasma hepcidin that blocks transfer of iron from macrophages to erythroid precursors
Is anemia of chronic disease macrocytic or microcytic?
Microcytic with low serum iron
What is the total iron binding capacity in anemia of chronic disease?
Decreased total iron binding capacity
Failure or suppression of stem cells leads to a hypocellular marrow