8/5- Sideroblastic and Megaloblastic Anemias Flashcards
Causes of microcytic anemia (broadly)?
- Iron deficiency anemia
- Sideroblastic anemia
- Thalassemias
- Anemia of chronic disease
What is sideroblastic anemia?
Disorders with finding of ring sideroblasts in the bone marrow
- Iron overload
- Impaired biosynthesis of heme
- Iron does not incorporate into protoporphyrin
- Builds up in mitochondrion
- Mitochondria encircle the erythroid progenitor nucleus- “ringed siderbolast” is a pathologic finding of large blocks of staining material (iron staining in normal erythroid progenitors shows up as blue dots “sideroblasts”- a normal finding)
**Ringed sideroblasts are pathologic findings whereas a sideroblast is a normal finding**
What does this show?
Bone marrow- sideroblastic anemia
What is a Peappenheimer body?
Iron seen in mature circulating RBCs
What does bone marrow show in sideroblastic anemia?
Bone marrow shows erythroid hyperplasis
- In effective erythropoiesis
- Signal to gut to increase iron absorption
Different forms of sideroblastic anemia?
Inherited (uncommon)
- Mostly X-linked ALAS2
Acquired:
- Drugs
- MDS
Characteristics of Congenital Sideroblastic Anemia?
- Most often X-linked
- Deficiency of RBC delta aminolevulinic acid synthase—the first enzymatic step in heme porphyrin production
- No Heme, no incorporation of iron into hemoglobin, iron builds up in the mitochondria
- Microcytic Anemia
- Pyridoxine is a cofactor of the enzyme and in some patients replacement improves the anemia
Characteristics of Hereditary Sideroblastic Anemia?
(only need to know the first one)
- X-linked: delta-ALA (dALA) synthase deficiency; pyridoxine may be effective
- Autosomal recessive
- Mitochondrial:
—Pearson’s Pancreatic Syndrome
—Abcb7 deficiency and ataxia
—Thiamine responsive megaloblastic anemia syndrome—TRMA
—MLASA-myopathy lactic acidosis-SA
What can lead to acquired sideroblatsic anemia?
- Alcohol
- Lead
- Copper deficiency (years after gastric bypass, zinc excess as from denture adhesive, peripheral neuropathy)
- INH if pyridoxine (B6) is not given
- Chloramphenicol (antibiotic still in use in underdeveloped countries)
If a pt presents with anemia, bilateral wrist drop and this peripheral blood smear, which of the following is most likely to be the cause of his anemia?
A. Copper
B. Gold
C. Lead*
D. Krypton
E. Silver
If a pt presents with anemia, bilateral wrist drop and this peripheral blood smear, which of the following is most likely to be the cause of his anemia?
A. Copper
B. Gold
C. Lead
D. Krypton
E. Silver
- Lead poisoning is associated with neuropathy—in this case foot drop. In children—often it is colic.
- Lead inhibits ALA dehydratase and also a house keeping enzyme 5’ nucleotidase. When the latter is inhibited RNA is not degraded and coarse basophilic stippling is found
- Iron deficient children have pica and may eat paint chips from old walls or cribs—and then get lead poisoning as well
- Note that fine basophilic stippling may just be an exaggerated form of the polychromasia seen with a reticulocyte.
- In children with relative iron deficiency lead further blocks iron absorption in the gut and sideroblasts may not be evident in the marrow.
What is characteristic of RBCs in Acquired Sideroblastic Anemia/Myelodysplastic Syndrome?
Dual population of RBCs:
- Microcytic RBCs are a sub-population
- Macrocytic RBCs predominate
- MCV is typically increased
Other characteristics of Acquired Sideroblastic Anemia/Myelodysplastic Syndrome?
Treatment?
- Pseudo Pelger Huet WBC in Myelodysplastic syndromes (more later)
- Increased serum iron, and increased % Sat
- High Ferritin
- Presence of Ringed Sideroblasts in bone marrow
Treatment: Pyridoxine, Erythropoietin, Transfusions
Case)
A 65-year-old black man, a retired minister, presents with anemia. He is diabetic but has done well on a diet. He is referred to you for evaluation of mild anemia: Hct 28 %, MCV 110, and folate, B12, and iron studies are normal. His physical exam is unremarkable, he has no splenomegaly……
?
What is this showing?
Peripheral blood film shows a dimorphic population of RBCs: hypochromic/microcytic and macrocytic
What is this showing?
Bone marrow aspirate show iron present in large chunks in a perinuclear distribution– consistent with mitochondrial iron (Perl’s Prussian Blue stain)
Differential Diagnosis of Sideroblastic Anemia?
Myelodysplaisa- clonal disorders of ineffective hematopoiesis
- SF3B1 mutation with pre mRNA splicing
- V617F JAK2 mutation with sideroblastic anemia and thrombocytosis
- Chromosomal changes
What are the levels of serum iron, TIBC, % saturation, and ferritin with the following:
- Iron deficiency
- Anemia of chronic disease
- Thalassemia minor
- Sideroblastic anemia
IMPORTANT SLIDE!!!
What are the cellular mechanisms behind megaloblastic anemias?
- DNA synthesis is impaired
- Arrest of cellular division
- Increased apoptosis
- Ineffective erythropoiesis
- Normal RNA synthesis and cytoplasmic differentiation
- Macrocytosis
- B12 and folate deficiency are the main causes
- Other tissues with rapid turn over may be affected
What does this show?
Megaloblatsic anemia
- Big red cells
- Hypersegmented neutrophils (from improper mitosis)
What does this show?
Macro-ovalocytosis
- Basophilic stippling
- Howell Jolly bodies
- Cabot rings (very very very rare)
What does this show?
Megaloblastic erythropoiesis
- Nuclear cytoplasmic dyssynchrony In megaloblastic states, there is delay in maturation of the nucleus, so cells that ought to be mature by looking at their cytoplasm have wide open young nuclei
- The cytoplasm matures but the nucleus does not divide—so you end up with a macrocyte.
What two key molecules are required for DNA synthesis?
- Folate
- B12 (cobalamin)
What is shown here?
Glossitis
- Gut may also be affected, and possibly abnormal pap smear
What effect does B12 deficiency have on the CNS (specifically spinal cord)
Combined systems disease, degeneration of:
- DC: balance issues, nighttime troubles
- Lateral CST
Flowchart of hypoproliferative/ineffective anemias
