PATH - Microcytic (MCV < 80 fL), hypochromic anemia

Question 1

Iron deficiency

Answer 1

DEC iron due to chronic bleeding, malnutrition, absorption disorders, or
INC demand (eg, pregnancy)–>*DEC final step in *heme synthesis.

fatigue, conjunctival pallor, pica (consumption of nonfood substances), spoon nails (koilonychia)

DEC iron
DEC ferritin
INC TIBC

can manifest as *Plummer-Vinson syndrome (triad of iron deficiency anemia, esophageal webs,
and dysphagia).

Question 2

α-thalassemia

Answer 2

Defect: *α-globin gene deletions–>DEC α-globin synthesis.

-4 allele deletion: No α-globin. Excess γ-globin forms γ4 (*Hb Barts). Incompatible with life (causes hydrops fetalis).
-3 allele deletion: inheritance of chromosome with cis deletion + a chromosome with 1 allele
deleted–>HbH disease. Very little α-globin. Excess β-globin forms β4 (HbH).
-2 allele deletion: less clinically severe anemia.
-1 allele deletion: no anemia (clinically silent)

• *cis deletion prevalent in *Asian populations
• *trans deletion prevalent in *African populations

Question 3

β-thalassemia

Answer 3

Point mutations in splice sites and promoter sequences–>DEC β-globin synthesis.

Prevalent in Mediterranean populations.

Question 4

β-thalassemia minor

Answer 4

heterozygote

β chain is underproduced

Usually asymptomatic

INC HbA2 (> 3.5%) on electrophoresis

Question 5

β-thalassemia major

Answer 5

homozygote

β chain is absent–>severe microcytic, hypochromic
anemia with *target cells and increased anisopoikilocytosis requiring blood transfusion
(2° hemochromatosis)

Marrow expansion (“crew cut” on skull x-ray)–>skeletal deformities
“Chipmunk” facies
Extramedullary hematopoiesis–>Žhepatosplenomegaly

INC HbF (α2γ2)

Question 6

HbS/β-thalassemia heterozygote

Answer 6

mild to moderate sickle cell disease depending on amount of β-globin production

Question 7

Lead poisoning

Answer 7

Lead inhibits *ferrochelatase and *ALA dehydratase Ž  heme synthesis and–>DEC RBC protoporphyrin.

Also inhibits rRNA degradation–>RBCs retain aggregates of rRNA (*basophilic stippling).

Symptoms of LEAD poisoning:
-Lead Lines on gingivae (Burton lines) and on metaphyses of long bones on x-ray.
ƒ-Encephalopathy and Erythrocyte basophilic stippling.
ƒ-Abdominal colic and sideroblastic Anemia.
ƒ-Drops—*wrist and foot drop. *Dimercaprol and *EDTA are 1st line of treatment.

Question 8

Sideroblastic anemia

Answer 8

Defect in *heme synthesis due to *X-linked defect in *δ-ALA synthase gene

*Ringed sideroblasts
*basophilic stippling
of RBCs.

INC iron
INC ferritin
normal/DEC TIBC

TX: pyridoxine