Module 1: Thalassemia and Iron deficiency Anemia

Question 1

Starting off with the microcytic hemolytic anemias is Alpha Thalassemia, what is the etiology of this?

Answer 1

Deletion mutations on chromosome 16 to any number of the 4 alpha globin genes, which leads to decreased synthesis of alpha globin and accumulation of unpaired Beta globin chains

Question 2

What are the four different types of Alpha Thalassemia?

Answer 2

1. Silent Carrier: 1 alpha gene deleted (Asymptomatic)
2. Alpha thalassemia trait: Two genes deleted
   - – alpha/alpha and -/- (SE Asian) CIS
   - – alpha/- and alpha/- (African) TRANS
   - –mild anemia with increased RBC count
3. Hemoglobin Hd: 3 genes affected; severe anemia
   - –B chain form tetramer (HbH) — high affinity O2 – severe tissue hypoxia
   - –HbH is prone to oxidation – precipitated inclusions in older RBCs — extravascular hemolysis
4. Hydrops Fetalis= lethal in utero; 4 genes deleted
   - -gamma chains form tetramers (Hb Barts) – extremely high affinity for 02 — no O2 reaches tissues

Question 3

The next hypochromic microcytic anemia is Beta Thalassemia, with extravascular hemolysis. What is the etiology of this anemia?

Answer 3

Decreased synthesis of structurally normal beta globin chains due to point mutations in chromosome 11 in promotor or splicing sites

Question 4

Inadequate levels of B-globin leads to what?

Answer 4

unpaired alpha globin chains

Question 5

Explain B+ and B0

Answer 5

B+ : decreased beta chains produced – mutation in promotor region of gene
B0: no beta chains (homozygous)-mutation in splicing or chain termination

Question 6

What types of ppl get beta thalassemia?

Answer 6

Mediterranean and S.E. asian males

–autosomal recessive

Question 7

There are two types of Beta thalassemia, what are these types?

Answer 7

Minor or Trait: B0/B or B+/B – mild asymptomatic anemia (one normal beta chain and one dimished (+) or absent (0) )
Major: B0/B0 or B+/B+ — severe transfusion dependent anemia (Abnormal in causes occlusion in small blood vessels)(no beta chains period)

Question 8

As mentioned before beta thalassemia major is predominately extravascular hemolysis, so therefore what signs will you see in the patient?

Answer 8

Splenomegaly (again this is happening in the spleen) causing a dragging pain in the LUQ
Chronic Hemolytic Anemia (spleen is destroying the RBCs)
—splenic macrophages are eating the defective RBC causing splenomegaly

Question 9

Beta thalassemia major also involves extramedullary hematopoiesis, what does this involve?

Answer 9

Eventually the liver and spleen starts compensating for the lysing and decreased RBC so more hematopoietic cells are made causing hepatosplenomegaly.
–also causes lymphadenopathy

Question 10

Patient with beta thalassemia major also have frontal bossing seen on examination (called crew cut appearance on xray) and chipmunk faces, what is this due to?

Answer 10

Expansion of the hematopoietic marrow in the skull via two mechanisms: 
Intramedullary hematopoiesis (erythroid hyperplasia): Bone marrow is making more reticulocytes due to increased destruction of RBCs. 
Intramedullary hemolysis (aka ineffective erythropoiesis): alpha chain tetramers break RBCs before they leave the marrow.

Question 11

What are other signs and symptoms in a patient with beta thalassemia?

Answer 11

Jaundice (Due to the unconjugated bilirubin)
Fatigue
Hepatomegaly
Failure to thrive in small kids

Question 12

Electrophoresis is the best investigation for beta thalassemia, what is seen?

Answer 12

Major: very prominent HbF and small amount of HbA2 (if B0/B0 then no HbA at all; if B+/B+ then a very small amount of HbA)
Minor: HbA2 small amount, small amount of HbF and still majority HbA

Question 13

What do you see on peripheral blood smear in a patient with thalassemia major?

Answer 13

• -Anisopoikilocytosis (RBCs of different shapes and sizes) causes an increase in RDW
• –Reticulocytosis (Due to the intramedullary hematopoiesis)
• –Target cells ( Hb settling in the center of the cell)
• –Normoblasts (due to the Intramedullary hemolysis )
• -Hypochromic microcytic RBCs (decreased MCHC due to decreased Hb and decreased MCV)
• -Howell Jolly Bodies (because the spleen is getting over worked)

Question 14

What is seen in regards to lab values in these patients?

Answer 14

Increased LDH
Increased Potassium
Increased Serum Iron
Increased Ferritin (protein that stores iron in the liver)
Increased reticulocytes
Increased RDW
Decreased TIBC (total iron binding capacity)

Question 15

Patients with beta thalassemia major need repeated blood transfusions, why?

Answer 15

Due to lack of HbA (worst type of anemia)

Question 16

What do patients with beta thalassemia major die from?

Answer 16

Most common cause of death is CHF secondary to hemochromatosis
—in a state of iron overload and keep getting blood transfusions so more and more overload of iron — decreased hepcidin

Question 17

What are the complications of beta thalassemia major?

Answer 17

1. Hemochromatosis: bronze skin, diabetes, arthritis, restrictive cardiomyopathy, liver cirrhosis, pseudogout
2. Shuts down anterior pituitary: no TSH so thyroid gland atrophies and therefore secondary hypothyroidism ; no LH so testicular atrophy and infertility; no ACTH so secondary adrenal cortical insufficiency so low cortisol
3. Bilirubin gallstones (Cholelithiasis)
4. Encapsulated bacterial infections
5. Aplastic crisis (Parvo B19 - causing reticulocytopenia)
6. Sepsis due to iron loving bacteria: Vibrio Vulnificus and Yersinia Enterolytica (mimics acute appendicitis)
7. Megoblastic anemia due to using up all the folate in the body

Question 18

What is treatment for beta thalassemia major?

Answer 18

Iron Chelators
Folate supplements
vaccinations
blood transfusions

Question 19

The next anemia that will be discussed is iron deficiency anemia, which is what type of anemia?

Answer 19

Microcytic Hypochromaic Anemia

Question 20

There are 4 etiologies for iron deficiency anemia each card will go through one. The first etiology is…

Answer 20

1. Nutritional deficiency: very common in children—most of iron intake is from meat as heme iron and grains as stored non heme iron so its okay to give kids meat.

Question 21

The 2nd etiology for iron deficiency anemia is….

Answer 21

2. Malabsorption: Iron is absorbed in duodenum
   - –Crohns Disease
   - -Celiac Sprue (gluten sensitive entropathy)
   - –Tropical Sprue (bacterial)
   - –Whipple’s (gram positive bacteria common in white men)

Question 22

3rd etiology for iron deficiency anemia is …

Answer 22

3. Increased demand
   - -pregnant women
   - -growing infants and children
   - -pre-menopausal women

Question 23

4th etiology for iron deficiency anemia is..

Answer 23

4. Chronic blood loss
   - –Right sided colon cancer (Due to occult blood)
   - –Uterine fibroids in nulliparous black women who get heavy periods
   - –Peptic ulcer causes melena
   - -Gastric cancer or esophagus cancers

Question 24

Plummer Vision Syndrome is super un common but happens mostly in middle aged women , what is the triad of etiologies?

Answer 24

1. Iron deficiency anemia (fatigue)
2. Glossitis: beefy tongue
3. Esophageal Webbing: dysphagia

Question 25

How does a patient with iron deficiency anemia present?

Answer 25

Just fatigue - -no jaundice due to no elevation in bilirubin - -no megaly - -normal urine - -normal LDH and bilirubin

Question 26

What is the best investigation for iron deficiency anemia?

Answer 26

Bone marrow biopsy with Prussian Blue staining (Way to invasive to do clinically) --hypocellular bone marrow because its a production problem not enough iron to make red cells.

Question 27

What are the lab values for a patient with iron deficiency anemia?

Answer 27

Storage Iron is depleted: so decreased ferritin and increased TIBC Serum Iron is depleted: low serum iron and low % saturation

Question 28

What is seen on peripheral blood smear in patients with iron deficiency anemia?

Answer 28

Poikilocytosis (elevated RDW) Pencil Red Cells Hypochromic (low MCHC--decreased Hb) Microcytic (low MCV--small RBC) Thrombocytosis (idiopathic--elevated platelet count) Reticulocytopenia (no iron to make reticulocytes)

Question 29

What are the complications for iron deficiency anemia?

Answer 29

1. CHF 2. Esophageal webs can become squamous carcinoma of the esophagus 3. Pica (eat soil/dirt) due to the chronic iron deficiency 4. Spooning of Fingernails: Koilonychia

Question 30

Pregnant women need iron supplements as well as what?

Answer 30

Vit C this is for them to be able to absorb iron in the duodenum

Question 31

What is the normal iron metabolism?

Answer 31

Iron is absorbed in the duodenum. Nonheme iron is carried across the apical and basolateral membranes of enterocytes by transporters - --after reduction by ferric reductase, ferrous iron (Fe2) is transported across the apical membrane - --A second transporter, ferroportin, then moves iron from the cytoplasm to the plasma across the basolateral membrane - -the newly absorbed iron is next oxidized by hephaestin and ceruloplasmin to ferric iron (Fe3), this binds to transferrin.

Question 32

What is the pathogenesis for iron deficiency anemia?

Answer 32

decreased iron ---- decreased heme ---- decreased hemoglobin --- microcytic anemia

Question 33

When the body is replete with iron, what happens?

Answer 33

Most iron entering duodenal cells is handed of to ferritin and transfer to plasma transferritin is enhanced when iron is deficient or erythropoiesis is inefficient

Question 34

Explain the role of hepcidin in iron?

Answer 34

A small hepatic peptide that is synthesized and secreted in an iron dependent fashion - -plasma hepcidin binds ferroportin and induces its internalization and degradation - -when hepcidin levels fall the basolateral iron is increased eventually leading to systemic iron overload