Anemia

Question 1

What is anemia

Answer 1

Anemia is the lack of normally formed, properly functioning RBCs in the circulation, which impairs the body’s ability to oxygenate the tissues at optimal level.

Question 2

Anemias may be qualitatively or quantitative or both. Meaning?

Answer 2

Quantitative: Decreased RBC count
Qualitative: Disordered cellular morphology or hemoglobin structure

Question 3

How can you see RBC abnormalities

Answer 3

CBC, hemoglobin electrophoresis, peripheral blood smear, bone marrow aspirate (rarely and if necessary)

Question 4

3 pathophysiologic mechanisms resulting in anemia

Answer 4

Underproduction of RBCs
Increased premature destruction of RBCs
Leakage out of circulation eg. in bleeding

Question 5

Cases where we see impaired marrow production

Answer 5

substrate deficiency states: iron/folate deficiency
Disorders of heme synthesis: sideroblastic anemia
Disorders of hemoglobin synthesis: Thalassemias
Impaired marrow responsiveness to erythropoietin: anemia of chronic disease
Bone marrow infiltrative conditions: malignancies
Conditions associated with reduced erythropoietin production: renal failure

Question 6

Where do we see increased RBC destruction?

Answer 6

Hereditary spherocytosis
sickle cell anemia
Glucose 6 phosphate dehydrogenase deficiency
Paroxysmal nocturnal hemoglobinuria (PNH)
Conditions leading to hypersplenism

Question 7

Hemolytic anemia?

Answer 7

Anemias in which RBC destruction (hemolysis) is the cause of the anemia.
Hereditary causes: spherocytosis, PNH, G6PD deficiency, sickle cell anemia

Acquired hemolytic anemias may be autoimmune, drug-induced or traumatic (mechanical prosthetic heart valves)

Question 8

Extravascular hemolysis?

Answer 8

RBCs are lysed outside the vasculature. Splenic macrophages or Kupffer cells in the liver destroy RBCs due to structural or morphological abnormalities

Hereditary spherocytosis, hypersplenism

Question 9

Intravascular hemolysis?

Answer 9

RBCs are directly lysed within blood vessels.
PNH,
mechanical fragmentation by prosthetic valves or by fibrin clot products (as in microangiopathic hemolytic anemias which occur in DIC),
TTP (thrombotic thrombocytopenic purpura)

Question 10

Haptoglobin

Answer 10

Serum protein that sops up free heme in circulation

Question 11

Hemoglobinemia and hemoglobinuria in intravascular vs extravascular hemolysis

Answer 11

In intravascular, lysed RBCs spill their hemoglobin directly into the bloodstream (hemoglobinemia), which may then be filtered out into the urine (hemoglobinuria)

In extravascular, the phagocytosed hemoglobin is metabolized intracellularly to bilirubin

Haptoglobin will be more decreased in intravascular hemolysis than extravascular

Question 12

MCV

Answer 12

Mean corpuscular volume
Used to determine RBC size
Calculated by dividing hematocrit by RBC count per liter
Normal reference range is 80-100fL

Question 13

Normocytic, Microcytic, Macrocytic

Answer 13

based on relation to MCV
Normocytic, within normal MCV range
Microcytic: below
Macrocytic: Above range

Question 14

Differentials for normocytic anemia

Answer 14

Anemia of chronic disease
Blood loss
Hemolytic anemias eg spherocytosis, PNH, G6PD deficiency, sickle cell anemia

Question 15

Types of hemoglobin

Answer 15

Hemoglobin A (alpha2beta2) 
Hemoglobin A2 (alpha2delta2)
Hemoglobin F (alpha2gamma2)

Question 16

Differentials for microcytic anemia

Answer 16

Sideroblastic anemia 
Lead poisoning 
Thalassemia 
Iron deficiency
Anemia of chronic disease

Question 17

Diagnosis if gel electrophoresis reveals elevated A2 and F and complete absence of beta globin subunits

Answer 17

Beta thalassemia major (Cooley’s anemia)

Normal serum iron, ferritin and TIBC

Question 18

Thalassemia major vs minor?

Answer 18

Zero vs partial expression of beta globin subunits

Minor is usually asymptomatic

Question 19

Alpha thalasemia

Answer 19

Caused by reduced or absent synthesis of alpha globing chains

African and Southeast basin descent

HbH, Hb Barts

Question 20

Structure of hemoglobin

Answer 20

Heme ring + 4 globing chains

Question 21

Transition from HbF to HbA

Answer 21

By approximately six months of age, healthy infants will have transitioned to mostly HbA, a small amount of HbA2, and negligible HbF

Question 22

Hemoglobin H

Answer 22

Alpha thalassemia intermedia

4 betas. No alpha globin chains produced

Hemolysis, severe anemia
Moderate to severe hemolytic anemia, modest degree of ineffective erythropoiesis, splenomegaly, variable bone changes

Question 23

Hb Barts

Answer 23

Alpha thalassemia major

4 gammas. No alphas. Hydrops fetalis. Incompatible with life

Question 24

Alpha globin chain production

Answer 24

controlled by two genes on each chromosome 16

A single gene deletion results in alpha thalassemia silent carrier status, which is asymptomatic with normal hematologic findings.

The two-gene deletion causes alpha thalassemia trait (minor) with microcytosis and usually no anemia.

The three-gene deletion results in significant production of hemoglobin H (HbH). Microcytic anemia, hemolysis, and splenomegaly.

The four-gene deletion results in significant production of hemoglobin Bart’s (Hb Bart’s),

Question 25

Beta thalassemia

Answer 25

deficient or absent synthesis of beta globin chains

Beta thalassemia occurs from any of more than 200 point mutations and (rarely) deletions of the two genes.

Question 26

Beta globin synthesis?

Answer 26

controlled by one gene on each chromosome 11

Question 27

Beta thalassemia types

Answer 27

The one gene defect, beta thalassemia trait (minor), is asymptomatic and results in microcytosis and mild anemia.

If the synthesis from both genes is severely reduced or absent, the person has beta thalassemia major, also known as Cooley anemia.
Symptoms: Anemia, jaundice, splenomegaly at 6 months due to switch from fetal to adult hemoglobin. Asymptomatic at birth

beta thalassemia intermedia: Two defective genes, but synthesis if beta chains is less severely reduced. Less severe symptoms. Do not require lifelong blood transfusions

Question 28

hemoglobin electrophoresis is usually normal in adults with alpha thalassemia trait.
T/F

Answer 28

True

Question 29

Persons with beta thalassemia major are diagnosed during infancy.
Y/N

Answer 29

Yes!

Pallor, irritability, growth retardation, abdominal swelling, and jaundice appear during the second six months of life

Question 30

complications that occur with beta thalassemia major or intermedia

Answer 30

overstimulation of the bone marrow, ineffective erythropoiesis, and iron overload from regular blood transfusions.

With multiple blood transfusions and continued absorption of intestinal iron, iron overload develops. Iron is deposited in visceral organs (mainly the heart, liver, and endocrine glands), and most patient deaths are caused by cardiac complications.

Question 31

In Beta thalassemia major, which becomes the dominant hemoglobin

Answer 31

HbF

Question 32

Complications of iron overload

Answer 32

Liver disease, pancreatic dysfunction (diabetes mellitus), cardiomyopathy

Chelation therapy is treatment for iron overload