Anemia: Microcytic, Normocytic, and Macrocytic

Question 1

Iron Deficiency

• What is the clinical manifestation
• Histologic Findings

Answer 1

Microcytic Anemia:

• Plummer-Vinson Syndrome: Triad of iron deficiency anemia, esophageal webs, and atrophic glossitis
• More SX: Fatigue, conjunctival pallor, spoon nails (koilonychia)
• Histological: Microcytosis and hypochromia

Question 2

Alpha-Thalassemia

Answer 2

Microcytic Anemia:

• Alpha Globin Gene deletion: Decrease Synthesis
  
  • Cis deletion: Asians
  • Trans deletion: Africans
• Ranges from 1-4 allele deltion.
  
  • 3 allele deletion: HbH disease, excess beta globin
  • 4 allele deletion: Excess gamma globin (Hb Barts). Incompatible with life, causes hydrops fetalis

Question 3

Beta-thalassemia

Answer 3

Microcytic Anemia:

• Decrease beta-globin synthesis
• Prevalent in Mediterannean populations

Major vs Minor Form

• Major = absent beta chain, severe anemia.
  
  • Sx: “Crew Cut” on x-ray => skeletal deformities “Chipmunk” facies.
  • Sx: Extramedullary hematopoiesis leading to hepatosplenomegaly
  • Sx: Increase Risk of parvovirus B19 induced aplastic crisis
  • Lab: Increase HbFetal (alpha and gamma)
• Minor = Underproduced beta chain, usually asymptomatic
  
  • ​Dx Confirmation: Increase HbA2 (> 3.5%)

Question 4

Lead Poisoning

Answer 4

Microcytic Anemia:

• Lead inhibits ferrochelatase and ALA dehydratase => decrease heme synthesis and increase Protoporphyrin

Symptoms: LEAD

L = Lead Lines on gingivae (Burton lines) Metaphyses

E = Encepahalopathy and Erythryocyte Basophilic Stippling

A = Abdominal Colic and siderblastic Anemia

D = Drops (Wrist and foot drop). 1st line tx: Dimercaprol and eDta

Note: Succimer used for chelation for kids.

Question 5

Sideroblastic Anemia

Answer 5

Microcytic Anemia

• If Genetic: X-linked defect in delta-ALA synthase gene which affects delta-aminolevulinic acid synthase (rate limiting step)
• Labs: Increase iron, Normal/decreased TIBC, Increase ferritin (basically opposite of iron deficiency)
• Tx: Pyridoxine

Question 6

Megaloblastic Anemia

Answer 6

Macrocytic Anemia

• Impaired DNA synthesis: maturation of nucleus is delayed releative to maturation in cytoplasm
• RBC Macrocytosis, hypersegmented neutrophils, glossitis

Question 7

Folate Deficiency vs B12 (cobalamin deficiency)

Answer 7

Macrocytic Anemia

• Folate Deficiency
  
  • increase homocyestine, normal methylmalonic acid, NO neurologic symptoms
• B12 (cobalamin) deficiency
  
  • increase homocyestine, increase methylmalonic acid, neurolgic symtpoms (B12 is involved in myelin synthesis and fatty acid pathway)

Question 8

Orotic Aciduria

Answer 8

Macrocytic Anemia

• Orotic Acid in Urine, no hyperammonemia
  
  • (vs. orinthine transcarbamylase deficiency which has increase orotic acid with hyperammonemia)
• Tx: Uridine monophosphate (to bypass mutated enzyme)

Question 9

Nonmegaoloblastic macrocytic anemia

Answer 9

Macrocytic anemia

• Macrocytic but DNA synthesis is unimpaired
• Causes: Alcoholism and liver disease mostly
• Sx: RBC macrocytosis w/o hypersegmented nuetrophils
• Drugs: 5 fluorouracil, Zidovudine, Hydroxyurea

Question 10

Anemia of Chronic Disease

Answer 10

NONhemolytic, normocytic anemia

• Inflammation => Increase hepcidin which binds to ferroportin and decreases released of iron from macrophages
• Labs: Decrease iron, Decrease TIBC, Increase Ferritin
• Tx: EPO

Question 11

Aplastic Anemia

Answer 11

NONhemolytic, normocytic anemia

Caused by failure or destruction of myeloid stem cells

• Biggest cause: Radiation
• Pancytopenia: Severe anemia, leukopenia and thrombocytopenia + Associated Sx.
• Sx: Hypocellular bone marrow with fatty infiltration

Question 12

Hereditary spherocytosis

Answer 12

INTRINSIC Hemolytic nromocytic anemia

• Defect in RBC membrane proteins => premature removal by spleen
• sx: Splenomegaly + aplastic crisis (parvovirus B19)
• Labs: Osomotic fragility test (+)
• Tx: splenectomy

Question 13

G6PD Deficiency

Answer 13

INTRINSIC Hemolytic nromocytic anemia

• Oxidant Stress (Sulfa drugs, antimalarials, infection, and fava beans)
• Labs: Heinz body and bite cells

“Stress makes me eat Bites of Fava Beans with Heinz ketchup”

Question 14

Paraoxysmal nocturnal hemoglobinuria

Answer 14

INTRINSIC Hemolytic nromocytic anemia

• complement mediated RBC lysis
• Triad: Coombs Test (-), hemolytic anemia, pancytopenia, and venous thrombosis
• Labs: CD55/59 (-) RBCs on flow cytometry and Ham’s Test (+, RBC lysis at low pH)
• Tx: eculizumab

Question 15

Sickle Cell Anemia

Answer 15

INTRINSIC Hemolytic normocytic anemia

• HbS point mutation causes a single amino acid replacement in Beta Chain (glutamic acid with valine)
• Pathogenesis: Low O2, high altitude, or acidosis = sickling.
• Sx: Crew Cut on skull x-ray, Salmonella osteomyilitis
• Tx: hydroxyurea (increase HbF)

Question 16

Autoimmune hemolytic anemia

Answer 16

EXTRINSIC Hemolytic normocytic anemia

• Coombs Test (+)
  
  • Direct = test blood, Indirect = test serum

Warm vs Cold Agglutinin

• Warm Agglutinin = “Warm weather is Great”
  
  • IgG, chronic anemia t
• Cold Agglutinin = “Cold weather is MMMiserable”
  
  • IgM, acute anemia
  • Triggered by cold, seen in CLL, Mycoplasma pneumonia and Mononucleosis

Question 17

Micro and Macroangiopathic Anemia

Answer 17

EXTRINSIC Hemolytic normocytic anemia

• RBCs are damaged when passing through obstructed or narrowed vessel lumina or prosthetic heart valves/arotic stenosis
• Shistocytes “helmet Cells”