BL Hassell lecture review

Question 1

Name hemoglobinopathies that have structural variants with abnormal function?

Answer 1

Hb S and Hb C

Question 2

Name hemoglobinopathies that have structural variants with decreased production of globin chains?

Answer 2

a thal and b thal

Question 3

Name hemoglobinopathies that have structural variants with decreased synthesis?

Answer 3

Hb E

Question 4

What are the normal percentages of adult hemoglobins (Hb A, A2, and F)?

Answer 4

A - 95 %, A2 - 3.5%, F - <2.0%

Question 5

Define Sickle cell disease.

Answer 5

Hemoglobinopathy with two abnormal Beta genes in which one contains the sickle cell mutation.

Question 6

Name the different Sickle cell diseases (in order of severity).

Answer 6

Hb S S = Hb S Bo thal; Hb S C; Hb S B+thal; Hb S A (trait). Not sure where to place Hb SE Hb SD, but be aware of their existence.

Question 7

Which physiological conditions promote sickling?

Answer 7

dec O2, inc K+, dehydration,

Question 8

Where are sickle cells most likely to manifest in the vasculature?

Answer 8

Post-capillary venules

Question 9

How do the sickle cells affect the carrier (4 things)?

Answer 9

Decreased ability to supply oxygen to tissues, abnormal cell adhesion to endothelium, direct damage to endothelium, abnormal vasoregulation.

Question 10

What other cell lines may be affected in sickle cell disease?

Answer 10

WBCs (elevation)

Question 11

Describe the ways to test for sickle cell disease (4 things).

Answer 11

Sickle solubility test (not reliable in distinguishing different types of sickling genotypes), hemoglobin separation (only gives % of types of Hb in sample as a whole). Isoelectric focusing and HPLC can give a better idea of percent of each type.

Question 12

Describe the hematologic (CBC and smear) findings of sickle cell disease.

Answer 12

CBC: NORMOCYTIC ANEMIA - Dec RBC, increased retics and robust retic response, inc WBC, inc platelets, inc LDH, inc bili, inc AST. Smear: sickle cells, cell fragments, polychromasia, Howell-Jolly bodies, nucleated RBCs

Question 13

Describe the organ level findings of sickle cell disease.

Answer 13

May see hepatosplenomegaly, overwhelming infections, infarctions and dead tissue in lungs, brain, retinas, kidneys, intestines, avascular necrosis of head of the femur, ulcers, pain, priapism.

Question 14

Which organ are uncommonly involved in sickle cell disease?

Answer 14

Heart and liver, although injury to these tissues is not impossible.

Question 15

Describe the mechanism of vascular injury in sickle cell disease.

Answer 15

The sickle cells may cause vascular injury due to shape and stickiness. The damage to endothelial cells results in tissue hypoxia, cytokine release, decrease in NO release, and vasoconstriction. These things all result in further damage to endothelial cells by sickle cells.

Question 16

Describe treatments for sickle cell disease

Answer 16

Supply adequate oxygen and improve hydration, treat any infections with antibiotics, give arginine to enhance vasodilation, may need to do blood transfusion, may need to give hydroxyurea, may need to do bone marrow transplant

Question 17

Name the risks of transfusion therapy.

Answer 17

Iron overload, alloimmunization (transfusion reactions), infection

Question 18

Describe the pathophysiology of thalassemia.

Answer 18

Primarily causes decreased synthesis of a or b globin chain. This leads to free chains that bind to RBC membrane (precipitation as Heintz bodies), cause membrane injury, cause decreased membrane stability.

Question 19

Describe the hematologic findings of a thal.

Answer 19

MICROCYTIC ANEMIA - inc RBC, dec MCV, dec MCH, inc RDW, robust reticulocyte response, inc bili, inc LDH, inc AST. Smear: target cells, hypochromia, microcytosis

Question 20

Describe the organ level findings of a thal.

Answer 20

Possible spelomegaly, cholelithiasis, and cholecystitis.

Question 21

What are the possible genotypes of a thal syndrome?

Answer 21

-1 a, -2 a, -3 a (aka Hb H), -4 a (hydrops fetalis)

Question 22

Which races are tend to be associated with thals? (important for classic USMLE questions)

Answer 22

Mediterranean, african, and asian

Question 23

How can we diagnose thals?

Answer 23

Hematologic findings (microcytosis, anemia), hemoglobin electrophoresis, diagnosis of exclusion (microcytosis without iron deficiency)

Question 24

Which thalassemia will not show up in examination of electrophoresis?

Answer 24

A thal. All hemoglobin contains a globin. The decrease in each type of hemoglobin will therefore be proportional in a thal disease.

Question 25

What are the possible genotypes of b thal syndrome (in order of severity)?

Answer 25

1 abnormal or absent beta gene, Hb EE, Hb E+severe or absent beta gene, 2 abnormal beta genes, Hb E+1 abnormal beta gene, 2 absent or severely abnormal beta genes

Question 26

Describe the hematologic findings of b thal.

Answer 26

MICROCYTIC ANEMIA - inc RBC, dec MCV, dec MCH, inc RDW, robust reticulocyte response, inc bili, inc LDH, inc AST. Smear: target cells, hypochromia, microcytosis. These findings will be exacerbated with stressors

Question 27

Describe the organ level findings of b thal.

Answer 27

May see splenomegaly/hypersplenism, growth delay. With Cooley?s anemia will see expanded marrow and osteopenia, additionally.

Question 28

Thalassemia major ia also know as? (bonus: what is its genotype?)

Answer 28

Cooley?s anemia. Bonus - two severely abnormal BETA globin genes

Question 29

Describe the electrophoresis findings of b thals.

Answer 29

Will seen an increase in Hb A2 and Hb F. How is this different than a thal electrophoresis findings?

Question 30

What condition can complicate the diagnosis of thalassemia?

Answer 30

Anemia. Why? Anemia is not a typical finding of thalassemia. May disguise a b thal disease. May also result in over supplementation of iron.

Question 31

What is hemoglobin Barts?

Answer 31

Four gamma globin chains. Will be seen in hydrops fetalis.

Question 32

Which hemoglobinemia will show only Hb F in neonatal screening?

Answer 32

Homozygous Beta-0 hemoglobin

Question 33

What types of hemoglobin will an normal infant have?

Answer 33

Hb F and Hb A

Question 34

Which type of thalassemia will show normal hemoglobin in neonatal screening?

Answer 34

B+ thal (mild to moderate beta thal mutations)