Inherited Red Cell Disorders

Question 1

3 main components of an RBC

Answer 1

Membrane
Hemoglobin
Enzymes

Question 2

What will you see in hemolytic anemia

Answer 2

Decreased hemoglobin concentration
Increased red cell breakdown (hyperbilirubinemia, cholelithiasis)
Increased bone marrow compensation (reticulocytosis, splenomegaly)

Question 3

What is the main genetic driving force for red cell disorders?

Answer 3

Malaria

Question 4

Hereditary spherocytosis

Answer 4

Mutations in “vertical” support components (ankyrin, spectrin, Band 3, protein 4.2)
Spherocytes are rigid and have decreased deformability, easily bursts and causes hemolysis

Question 5

What is splenic conditioning?

Answer 5

Seen in hereditary spherocytosis

Progressive loss of the membrane during each cycle through the spleen

Question 6

Hereditary spherocytosis inheritance pattern

Answer 6

75% autosomal dominant

25% autosomal recessive

Question 7

Symptoms triad of hereditary spherocytosis

Answer 7

Anemia
Jaundice
Splenomegaly

Question 8

3 ways hereditary spherocytosis is diagnosed

Answer 8

Blood smear
Osmotic fragility test
Flow cytometry

Question 9

How to manage hereditary spherocytosis

Answer 9

Supportive treatment (folic acid, spleen protection)
Splenectomy is a symptomatic cure (but need to give vaccines before)

Question 10

Beta thalassemia major

Answer 10

Mutation in beta globin
Decreased beta globin production causing imbalance between alpha and beta pairing
Excess alpha chains precipitates damaging red cell membrane
Ineffective erythropoiesis
Severe anemia after 6 months old, marrow expansion, hepatosplenomegaly

Question 11

Complications from beta thalassemia

Answer 11

Marrow expansion: osteoporosis
Endocrine failure: hypogonadotrophic hypogonadism, hypotheyroidism, ovarian failure
Transfusion hemosiderosis: CHF, liver cirrhosis, liver carcinoma
Transfusion related complications: infections, transfusion reactions
Psychosocial impact

Question 12

Management of beta thalassemia major

Answer 12

Need to start regular transfusion by 6-12 months
Blood transfusions every 3-4 weeks - high iron deposition
Needs iron chelation meds after 20 transfusions
Good transfusion and chelation and they will be fine

Question 13

Sickle cell anemia

Answer 13

Single nucleotide change (glu to val)
Hb S polymerizes when deoxygenated
RC becomes stiff and deformed
Sludging in capillaries (leads to recurrent infarctions - tissues can die and get inflammed which causes pain)

Question 14

Vaso-occlusive crises

Answer 14

In sickle cell anemia
Extreme excruciating pain in long bones, back or abdomen
Treat early, prevent it from happening

Question 15

Acute chest syndrome

Answer 15

From sickle cell disease
Sickling in lungs
Vicious cycle
Most common cause of death
Lung collapses and you become hypoxic
Need early transfusions, spirometry, and ventilation

Question 16

What is the definitive diagnosis for sickle cell anemia

Answer 16

Hb electrophoresis

Question 17

Management of sickle cell anemia

Answer 17

Comprehensive care program
Supportive (hydration, pain control)
Prevent and treat infections
Drug: hydroxyurea
Blood transfusions (but dont over do it!!)

Question 18

GP6D Deficiency

Answer 18

Unstable enzyme
Sex linked inheritance (more common in boys)
Reduced glutathione in red cells
Oxidation of Hb and oxidative damage of membrane (oxidative hemolysis)
RC damage - bite cells, blister cells - intravascular hemolysis
Diagnose via enzyme assay

Question 19

Management of GP6D Deficiency

Answer 19

Avoid fava beans, oxidizing drugs
Vigilance during severe infections
Treatment of acute hemolysis (self limiting) - hydration, alkalinization

Question 20

Pyruvate kinase deficiency

Answer 20

Final rate-controlling step in glycolysis
ATP depletion - decrease membrane ionic pumps = ionic leak and dehydration - hemolysis
Increased intracellular 2.3-DPG - right shift of oxygen dissociation curve - increased oxygen unloading - better tolerance to anemia

Question 21

What will you see in a pyruvate kinase deficiency

Answer 21

Neonatal jaundice (some elevation of conjugated bilirubin)
Life long anemia, but well tolerated
Mild jaundice, cholelithiasis
Supportive management (splenectomy usually not helpful, transfusion may be needed at times)