RBC Disorders - Anemia, Microcytic

Question 1

Anemia Basics

Answer 1

Reduction in circulating RBC mass
Signs and symptoms of hypoxia
Males: Hb< 13.5 (13.5-17.5)
Females: Hb<12.5 (12.5-16)
Microcytic: MCV < 80
Normocytic: MCV 80-100
Macrocytic: MCV > 100

Question 2

Microcytic Anemias

Answer 2

MCV <80
hypochromic
Iron deficiency (late), ACD (late), Thalassemias, Lead poisoning, Sideroblastic anemia
Decreased production of Hg (decrease in hemoglobin, heme, globin, iron, and/or protoporphyrin)
Microcytosis due to extra division that occurs to maintain Hg concentration

Question 3

Iron Deficiency Anemia

Answer 3

v iron due to chronic bleeding, malnutrition, absorption disorders, or ^ demand (pregnancy) –> v final step in heme synthesis

LABS: v iron, ^TIBC, v ferritin, v %sat, ^ FEP
Microcytosis, hypochromasia (central pallor) w ^RDW

Symptoms: fatigue, conjunctival pallor, pica (chew nonfood things abnormally), spoon nails (koilonychia)

May manifest as Plummer-Vinson syndrome

Question 4

Plummer-Vinson Syndrome

Answer 4

Triad: Dysphagia, Iron deficiency anemia, Esophageal webs (DIE)
beefy red tongue

Question 5

Iron Labs

Answer 5

Serum iron: iron in blood
TIBC: total iron binding capacity - transferrin molecules in blood
%saturation: percent transferrin bound by iron (normal=33%)
Serum ferritin: iron stores in macrophages and the liver - only diagnostic when low

Question 6

Stages of iron deficiency

Answer 6

1) storage iron depleted (v ferritin, ^TIBC)
2) serum iron depleted (v serum iron, v %sat)
3) normocytic anemia (bone marrow makes fewer, but normal-sized, RBCs)
4) microcytic, hypochromatic anemia (bone marrow makes fewer and smaller RBCs)

Question 7

Thalassemia

Answer 7

Anemia due to decreased synthesis of the globin chains of Hb
Inherited mutation
Carriers protected from Plasmodium falciparum malaria
alpha and beta types
Normal Hb types: 1% HbF (a2, gamma2), 97% HbA (a2, B2), 2% HbA2 (a2, delta2)

Question 8

a-thalassemia

Answer 8

a-globin gene deletions –> v a-globin synthesis
cis deletion - Asians
trans deletion - Africans

4 allele deletion: no a-globin; excess gamma-globin forms gamma4 (Hb Barts); incompatible w life (hydrops fetalis)

3 allele deletion: inheritance of cis deletion chromosome + chromosome w 1 allele deleted –> HbH (B4) disease; very little a-globin, excess B-globin forms B4

2 allele deletion: less clinically severe anemia

1 allele deletion: no anemia; clinically silent

Question 9

B-thalassemia (general, minor, heterozygote)

Answer 9

point mutation in splice sites and promoter sequences –> v B-globin synthesis
Mediterranean populations

minor: heterozygote, B-chain is underproduced; usu asymptomatic; diagnosis confirmed by ^HbA2 (>3.5%) on electrophoresis

HbS/B-thalassemia heterozygote: mild to moderate sickle cell disease depending on amount of B-globin production

Question 10

B-thalassemia major

Answer 10

homozygote
B-chain is absent –> severe microcytic, hypochromic anemia w target cells and ^anisopoikilocytosis (varied size and shape of RBCs) requiring blood transfusions (secondary hemochromatosis bc every bag of blood is bag of iron–> iron build-up)

Marrow expansion (crew cut skull on x-ray) –> skeletal deformities
Chipmunk facies
Extramedullary hematopoiesis –> hepatosplenomegaly
^ risk parvovirus B19-induced aplastic crisis

^HbF (fetal, a2 gamma2) - protective in infant and disease only becomes symptomatic after 6 months when HbF declines.

Question 11

Lead Poisoning

Answer 11

Lead inhibits ferrochelatase and ALA dehydratase –> v heme synthesis and ^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 metaphases of long bones on x-ray
Encephalopathy and Erythrocyte basophilic stippling
Abdominal colic and sideroblastic Anemia
Drops - wrist and foot drop. Dimercaprol and EDTA are 1st line tx

Succimer used for chelation for kids
Exposure risk ^ in old houses w chipped paint

Question 12

Sideroblastic Anemia

Answer 12

Defect in heme synthesis (specifically protoporphyrin) due to X-linked defect in ALA synthase gene –> protoporphyrin deficient and iron remains trapped in mitochondria

Causes: genetic, acquired (myelodysplastic syndromes), reversible (alcohol, lead, vitamin B6 deficiency, copper deficiency, isoniazid)

LABS: ^ iron, normal/v TIBC, ^ ferritin, ^ %sat
Ringed sideroblasts (w iron-laden, Prussian blue-stained mitochondria) in bone marrow
Peripheral blood smear: basophilic stippling of RBCs

Tx: pyridoxine (B6, cofactor for ALA synthase)

Question 13

Anemia of Chronic Disease

Answer 13

Chronic inflammation –> ^ hepcidin (released by liver, binds ferroportin on intestinal mucosal cells and macrophages, thus inhibiting iron transport) –> v release of iron from macrophages and v iron absorption from gut.
v available iron –> v heme –> v Hb

Assoc w rheumatoid arthritis, SLE, neoplastic disorders, chronic kidney disease

v iron, v TIBC, ^ ferritin, v %sat, ^ FEP
Normocytic early and microcytic late

Tx: EPO (chronic kidney disease only)

Question 14

Protoporphyrin/heme synthesis

Answer 14

Succinyl CoA –> (RLS!; ALA synthase, B6) ALA –> (ALAD) porphobilinogen –>–>–> protoporphyrin +Fe –> (in mitochondria; ferrochetalase) heme

Question 15

Lab Findings in Microcytic Anemia

Answer 15

Normal: ferritin(-), TIBC (300), serum iron (100), %sat (33)

Iron deficiency anemia: ferritin (v), TIBC (^), serum iron (v), %sat (v)

ACD: ferritin (^), TIBC (v), serum iron (v), %sat (v)

Sideroblastic anemia: ferritin (^), TIBC (v), serum iron (^), %sat (^)

Pregnancy/oral contraceptives: ferritin (-), TIBC (^), serum iron (-), %sat (v)