Heme #1: Microcytic Anemias

Question 1

MCC of anemia worldwide is _________

Etiologies include…

Risk factors include

Answer 1

-Iron deficiency anemia

-Chronic blood loss MCC in US: menstruation, Colon cancer, hookworms in resource-poor countries
-decreased absorption (diet) MCC worldwide: Celiac, H. Pylori, bariatric surgery

-increased metabolic requirements: children, pregnant, lactating women
-cow milk ingestion in young children < 1 year old

Question 2

Why does iron deficiency anemia occur (Patho)?

Symptoms of iron deficiency anemia

Answer 2

-Decreased RBC production due to lack of iron and decreased iron stories (ferritin).

-Pasophagia (craving for ice), Pica (craving for starch, clay), koilonychia (spooning of nails), angular chelitis, tachycardia, glossitis, pallor, poor concentration, irritability, restless legs syndrome

Question 3

What do the labs for iron deficiency anemia show?
-CBC
-Iron studies

What is the definitive diagnostic for IDA?

Answer 3

-CBC: microcytic hypochromic anemia. Increased RDW.
-Iron studies: decreased ferritin***, increased TIBC (transferrin), decreased transferrin saturation, decreased serum iron.

Bone marrow biopsy: absent iron stores (definitive), but rarely done.

Question 4

What is the treatment for iron deficiency anemia and what are some recommendations to taking the medication/supplement?

Answer 4

-Iron replacement (ferrous sulfate orally).
-Take with Vitamin C (ascorbic acid), with water or orange juice, and on an empty stomach. Give 2 hours before or 4 hours after ingestion of antacids.
-RBC transfusion if severe

Question 5

What is microcytic?
What is normocytic?
What is macrocytic?

Answer 5

-Micro: < 80
-Normo: 80-100
-Macro: > 100

Question 6

Lead Poisoning Anemia
-Patho
-Risk Factors (who MC in)
-Sources

Answer 6

-Patho: Lead poisons enzymes causing cell death. Shortens life span of RBCs, inhibits enzymes needed for heme synthesis.

-RF: MC in children (<6 years old)

-Sources: inhalation of environmental lead (paint chips or lead dust) especially if the house was built prior to the 1970’s.

Question 7

Symptoms of lead poisoning anemia
-think specific symptoms

Answer 7

-Neuro: ataxia, fatigue, concentration, learning problems, peripheral neuropathy (wrist or foot drop), encephalopathy

-Intermittent abdominal pain, vomiting, loss of appetite, constipation.

-Burton’s line: thin, blue-black line at base of gums in adults

Question 8

What do diagnostics for lead poisoning anemia show?
-Peripheral smear/CBC
-Lead
-Iron studies
-Radiographs

Answer 8

-Microcytic hypochromic anemia with basophilic stippling (dots of denatured RNA seen in RBCs). Ringed sideroblasts in bone marrow.
-Serum lead levels > 10 mcg/dL (capillary fingerstick)
-Normal/High serum iron, decreased TIBC
-Lead lines: linear hyperdensities at metaphyseal plates in children

Question 9

Management for lead poisoning anemia
-Mainstay
-Mild (44 or lower)
-Moderate (45-69)
-Severe (70 or higher)
–without encephalopathy
–with encephalopathy

Answer 9

-Removal of source of lead
-Mild: outpatient follow up and lifestyle changes
-Mod: Succimer
-Severe w/o: Succimer + calcium disodium edetate
–with enceph: Dimercaprol + calcium disodium edetate

Question 10

How does Succimer work for lead poisoning anemia?

Answer 10

-Forms water soluble chelates, and therefore, increases urinary excretion of lead.

Question 11

What is thalassemia?

Normally after what age is adult Hgb the predominant Hgb produced?

When should you suspect a thalassemia?

Answer 11

decreased production of globin chains

After 6 months of age

Microcytic anemia with normal/increased serum iron or no response to Fe treatment

Question 12

Alpha Thalassemia
-What is it?
-MC in what population?
-Explain 1-4 abnormal alleles and presentation

Answer 12

-Decreased alpha-globin chain production. 4 genes determine it.
-MC in SE Asians

-Alleles
–1 abnormal: silent carrier, asymptomatic
–2: Minor (trait)
–3: Intermedia (like B-Thalassemia Major)
–4: Hydrops Fetalis: stillbirth: Hgb Barts (gamma tetramers)

Question 13

Diagnostics for Alpha Thalassemia and what do they show?

Answer 13

-Hemoglobin electrophoresis
–1 & 2 gene deletion: normal Hb ratios in adults
–3: HbH (beta chain tetramer) = Heinz bodies
–4: Hgb Barts (gamma tetramers)

-DNA analysis is definitive

Question 14

What distinguishes alpha from beta thalassemia?

Answer 14

Alpha, in 1-2 gene deletions, has normal Hb ratios in adults. In Beta, HgbA is decreased, or little to none.

Question 15

Explain why the thalassemias are seen as a hemolytic anemia

Answer 15

-Beta chain tetramers (Heinz bodies) are produced, which have no oxygen carrying capacity and therefore, the RBCs are destroyed by the spleen.

Question 16

Symptoms of Alpha Thalassemia Intermedia (Hemoglobin H Disease)

Answer 16

-Symptomatic at birth (neonatal jaundice and anemia)
-Anemia symptoms (pallor, fatigue)
-Frontal bossing, maxilla overgrowth (increased bone marrow hematopoeisis)

Question 17

What does a CBC and peripheral smear for alpha thalassemia show?

Hemoglobin electrophoresis?

Answer 17

-Microcytic hemolytic anemia (schistocytes, tear drop cells, increased reticulocytes), target cells, increased RBC count, decreased hemoglobin (7-10).
-Hemolysis: increased indirect bilirubin, decreased haptoglobin

-Electrophoresis: presence of HbH (beta chain tetramer)

Question 18

Explain what happens in a hemolytic anemia to indirect bilirubin, haptoglobin, LDH, and reticulocytes.

Answer 18

-Haptoglobin decreased: becomes depleted when it binds to free hemoglobin with continued RBC destruction.
-Indirect bilirubin: increased due to RBC destruction, which overwhelms liver’s ability to convert it to direct.
-LDH: increased because it is an enzyme that is released from destroyed RBCs
-Reticulocytes: immature RBCs released due to RBC destruction.

Question 19

Management for alpha thalassemia

Answer 19

-Episodic blood transfusions during periods of infection, pregnancy, etc.
-Vitamin C and folate supplementation (helps make RBCs)
-Iron chelating agents (Deferoxamine) to remove excess iron from chronic infusions.
-Bone marrow transplantation is definitive if the patient has major.

Question 20

Beta Thalassemia
-What is it?
-MC in what population?

Answer 20

-Decreased production of beta-globin chains, leading to excess alpha chains
-MC in Mediterranean (Greek, Italian, etc.)

Question 21

Symptoms of Beta Thalassema based on abnormal alleles
-Minor (Trait): 1 abnormal
-Major (Cooley’s Anemia): 2 abnmormal

When do symptoms of Major start to occur? Why?

Answer 21

Minor: MC type: Asymptomatic or mild anemia

Major: Alpha chains that cannot form tetramers.
–Anemia: severe, chronic. Pallor, dyspnea, mental delays. Hemolytic anemia: Jaundice, hepatosplenomgaly.
–Extremedullary hematopoeisis: bony abnormalities, frontal bossing, hair on end appearance, osteoporosis, abnormal ribs.
–Osteoporosis: by age 10, compression fractures, scoliosis, disc degeneration.
–Endocrine abnormalities due to iron overload: DM, growth failure, hypogonadism
–Enlarged kidneys
–Cardiac dysfunction: heart failure, arryhthmias

Symptoms occur after 6 months of life after fetal hemoglobin replaced with adult.

Question 22

Hemoglobin electrophoresis of Beta Thalassemia
–HgbF vs HgbA
-Minor:
-Major:

What do radiographs of the skull show?

Answer 22

Minor: high HgbF and low HgbA
Major: high HgbF and little/none HgbA

Bossing with hair on end appearance (due to extramedually hematopoeisis)

Question 23

Management for Beta Thalassemia
-Minor
-Major

Answer 23

-Minor: no treatment needed, genetic counseling

-Major: Frequent transfusions, iron chelating agents, vitamin C and folate supplementation, splenectomy in some cases