RBC Membrane, Enzyme Disorders, and Megaloblastic Anemia

Question 1

6 causes of spherocytosis

Answer 1

HS
Immune mediated hemolytic anemia
CAD
Thermal burns
Snake bites, scorpion, brown recluse
Clostridium sepsis

Question 2

Inheritance and defect seen in hereditary spherocytosis

Answer 2

AD defect in proteins involved in vertical associations that link RBC membrane cytoskeleton and lipid bilayer. Ankyrin (50%), band 3 (25%), spectrin (20%), and protein 4.2 (5%). The reduced deformability of spherocytes makes them more prone to hemolysis and are then phagocytosed by splenic macrophages

Question 3

50 year old man presents with Hgb 5.2, low haptoglobin, elevated LDH, elevated indirect bilirubin, some mild splenomegaly. Spherocytes seen on peripheral smear. Has had similar but more mild episodes earlier in life. Most likely diagnosis and diagnostic testing?

Answer 3

HS
Osmotic fragility or EMA binding

Question 4

Management of hereditary spherocytosis

Answer 4

Transfusions as supportive
Splenectomy potentially

Question 5

Inheritance and defect in hereditary elliptocytosis or ovalocytosis

Answer 5

AD inherited defect in proteins assocaited with horizontal associations in RBC membrane and cytoskeleton. Mainly spectrin

Question 6

What is the most severe form of hereditary elliptocytosis

Answer 6

Hereditary pyroprokilocytosis

Question 7

Clinical and smear features of hereditary pyropoikilocytosis

Answer 7

Variable hemolysis but worse in early childhood. VERY low MCV (30-50s), peripheral smear with bizarre shapes

Question 8

Peripheral smear finding that is suggestive of G6PD deficiency?

Answer 8

Bite cells (blister cells)

Question 9

When suspecting someone of G6PD deficiency, when is not a good time to check G6PD levels?

Answer 9

During acute hemolysis. Reticulocytes have increased amounts of G6PD in them and can give false normals

Question 10

Inheritance of pyruvate kinase deficiency

Answer 10

AR

Question 11

Clinical features, epidemiology, smear findings of pyruvate kinase deficiency

Answer 11

Moderate hemolytic anemia at baseline, episodes of acute worsening. Smear is not impressive. High prevalence in Amish population

Question 12

Treatment for pyruvate kinase deficiency

Answer 12

Mitapivat (PK activator)

Question 13

What is the enzyme deficiency seen in lead poisoning?

Answer 13

Pyrimidine 5’ Nucleotidase

Question 14

You see a young man with hemolytic anemia and acute confusion. Platelet count and coags are normal. Smear shows basophilic stippling. Lead levels are normal. Diagnosis?

Answer 14

Pyrimidine 5’ Nucleotidase deficiency

Question 15

You see a patient with macrocytic anemia with MCV 114. LDH is elevated, bilirubin slightly elevated as well. Peripheral smear shows hypersegmented neutrophils and nuclear:cytoplasm dyssynchony. Next diagnostic step?

Answer 15

B12 and folate levels

Question 16

Methylmalonic acid levels are ________ in B12 deficiency

Answer 16

elevated

Question 17

Methylmalonic acid levels are _______ in folate deficiency

Answer 17

Normal

Question 18

You see a young patient with pancytopenia. Smear shows ringed sideroblasts and bone marrow has some hints dysplasia seen in erythroid precursors. Cytogenetics are normal, no genetic abnormalities seen. He has some peripheral neuropathy. Most likely diagnosis?

Answer 18

Copper deficiency