Microcytic Anemia II Flashcards by Karin Golob

How does a patient present with anemia?

They present with signs of hypoxia:

Weakness, fatigue, and dyspnea
Pale conjunctiva and skin
Headache and lightheadedness
Angina, especially with preexisting CAD

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What are the Hgb levels considered to be anemic for males and females?

Males: Hgb < 13.5g/dl

Females: Hgb < 12.5g/dl

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What is the anemia for:

MCV < 80

MCV = 80-100

MCV > 100

MCV < 80: Microcytic

MCV = 80-100: Normocytic

MCV > 100: Macrocytic

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Why do microcytic anemias occur?

Microcytosis is due to an “extra” division in hematopoesis

this is due to decreased production of Hgb
the cell wants to maintain normal concentrations of Hgb

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What is in the differential diagnosis of a person with low Hgb and an MCV < 80?

- Iron deficient anemia

- Anemia of chronic disease
(pt is in a state of chronic inflammation and iron is “locked” in macrophages)

- Sideroblastic anemia
(decreased production of protoporphyrin leads to low heme, leads to low Hgb)

- Thalassemia
(decreased production of globin chain = decreased hemoglobin)

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What is the most common type of anemia?

Iron deficiency anemia

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Where does absorption of iron occur?

In the duodenum

Enterocytes transport iron into blood via ferroportin
Transferrin transports iron and delivers it to liver and bone marrow macrophages for storage
Stored intracellular iron is bound to ferritin

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What molecule is iron bound to in the blood?

Transferrin

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What is iron bound to in the macrophage?

Ferritin

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What does serum iron measure?

The level of iron in the blood

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What does TIBC measure?

Total Iron Binding Capacity:

Measures transferrin in the blood (bound or unbound)

% saturation measures how much of that transferrin is bound to iron

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What does serum ferritin measure?

How much iron is present in bone marrow and liver macrophages

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How can a person become iron deficient?

What are the most common causes for:
Infants
Children
Adults
Elderly

Deficiency can be caused by dietary lack (malnutrition or malabsorption*) or blood loss

Infants = breast feeding (little to no iron in breast milk)

Children = poor diet

Adults = peptic ulcer disease (males); menorrhagia or pregnancy (females)

Elderly = Colon polyps/carcinoma (developed world); hookworm (developing world)

Gastrectomy can be a cause of increased Fe³⁺; Fe²⁺ is the form that is absorbed by the duodenum

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What are the stages of iron deficiency?

Storage iron depleted (serum ferritin decreases; TIBC increases)

Serum iron depleted (serum iron levels decrease; %saturation decreases (< 33%))

Normocytic anemia (bone marrow produces normal sized RBCs, just less of them)

Microcytic, hypochromic anemia (bone marrow is no longer able to make normal RBCs due to decreased iron/heme - central pallor of cells is enlarged due to decreased heme)

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What are clinical and lab features of iron deficiency?

Anemia

Koilonychia (spoon-shaped nails)

Pica (patients chew on things - dirt, ice, etc)

Microcytic, hypochromic anemia with Increased RDW

Decreased ferritin, Increased TIBC

Decreased serum iron, Decreased % saturation

Increased Free Erythrocyte Protoporphyrin (FEP; blood cell makes heme-iron = protoporphyrin)

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What is Plummer-Vinson syndrome?

Iron deficiency anema with esophageal web and atrophic glossitis

–> presents with anemia, dysphagia, and beefy-red tongue

What is anemia of chronic disease?

Chronic diseases with chronic inflammation results in acute phase reactants (i.e. Hepcidin)

Hepcidin sequesters iron into storage sites limiting iron transfers from macrophages to erythroid precursors
Hepcidin also suppresses EPO production from the kidney

What are the lab findings of anemia of chronic disease?

Increased ferritin (high stores of ferritin; sequestered by hepcidin)

Decreased TIBC

Decreased serum iron (it’s being used)

Decreased % saturation

Increased Free Erythrocyte Protoporphyrin (FEP)

What is the cause of sideroblastic anemia?

Defective protoporphyrin synthesis
(no protoporphyrin = no heme; no heme = microcytic anemia)

Iron is trapped in RBC mitochondria b/c heme is not produced and released
Iron laden mitochondria creates ringed sideroblast

What is the most common form of congenital sideroblastic anemia?

ALAS deficiency

Aminolevulinate synthase is rate limiting enzyme of protoporphyrin production:

Succinyl CoA –> Aminolevulinate
Enzyme: ALAS

What are the common causes of acquired sideroblastic anemia?

Alcoholism

Lead poisoning (Pb denatures ALAD and Ferrochelatase)

Vitamin B6 deficiency (ALAS requires B6 as a cofactor)

What are the laboratory findings of a sideroblastic anemia?

Increased ferritin, Decreased TIBC

Increased serum iron, Increased % saturation

Ringed sideroblasts have so much Fe that it starts to create free radicals, causing damage and killing the cell
- free iron is released and taken up by macrophages or leak into blood stream

How does thalassemia lead to a microcytic anemia?

Thalassemia results in a decreased synthesis of globin chains (as opposed to mutated globin chain like sickle cell)

Alpha thalassemia = decreased alpha globin
Beta thalassemia = decreased beta globin

–> decreased globin leads to decreased hemoglobin; resulting in microcytic anemia

Why has thalassemia not be selectively removed from the gene pool?

Carriers are protected against Plasmodium falciparum malaria

What are the three normal types of hemoglobin?

HbF (alpha₂gamma₂) HbA (alpha₂beta₂) HbA₂(alpha₂delta₂)

What is the cause of alpha-Thalassemia?

**--\> Due to a gene deletion** 1 Gene deletion = Asymptomatic 2 Gene deletion (cis or trans) = Mild anemia with slightly Increased RBC count; cis deletion is worse than trans due to increased risk in offspring 3 Gene deletion = Severe anemia; B chains form tetramers (HbH) that damage RBCs 4 Gene deletion = Hydrops fetalis; gamma chains of HbF form tetramers that damage RBCs | (there are normally 4 alpha alleles present on Chr16)

What are Hb Barts?

Tetramers of gamma chains seen on electrophoresis --\> signature of hydrops fetalis and 4 gene deletion alpha-Thalassemia

What is the cause of beta-thalassemia?

**Beta-thalassemia is due to gene mutations** (Normally, two beta genes are present on Chr11) - Mutations result in absent (ß^o) or diminished (ß⁺) production of ß-globin

What is Beta thalassemia minor?

ß/ß⁺ - Mildest form of disease (asymptomatic w/increased RBC count) - Microcytic, hypochromic RBCs and target cells

What does HgB electrophoresis show for beta thalassemia minor?

Slightly decreased HbA Increased HbA₂to 5% (normal 2.5%) Increased HbF to 2% (normal 1%)

What is Beta thalassemia major?

**ß^o/ß^o** - Most severe form of disease (no HbA) - Presents with **severe anemia and massive erythroid hyperplasia** a few months after birth (HbF is alpha₂gamma₂; doesn't require beta) - no functional beta chains results in alpha tetramers aggregating to damage RBC - -\> ineffective erythropoiesis - -\> extravascular hemolysis

What is massive erythroid hyperplasia? What result from this?

Expansion of hematopoeisis into marrow of skull ("crew cut" appearance on xray) and facial bones ("chipmunk" appearance) - Extramedullary hematopoiesis with Hepatosplenomegally b/c RBCs begin developing in liver and spleen - Risk of aplastic crisis with parvovirus B19