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Week 23: Anemia > Inherited Red Cell Disorders > Flashcards

Flashcards in Inherited Red Cell Disorders Deck (21)
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1

3 main components of an RBC

Membrane
Hemoglobin
Enzymes

2

What will you see in hemolytic anemia

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

3

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

Malaria

4

Hereditary spherocytosis

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

5

What is splenic conditioning?

Seen in hereditary spherocytosis
Progressive loss of the membrane during each cycle through the spleen

6

Hereditary spherocytosis inheritance pattern

75% autosomal dominant
25% autosomal recessive

7

Symptoms triad of hereditary spherocytosis

Anemia
Jaundice
Splenomegaly

8

3 ways hereditary spherocytosis is diagnosed

Blood smear
Osmotic fragility test
Flow cytometry

9

How to manage hereditary spherocytosis

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

10

Beta thalassemia major

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

11

Complications from beta thalassemia

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

12

Management of beta thalassemia major

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

13

Sickle cell anemia

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)

14

Vaso-occlusive crises

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

15

Acute chest syndrome

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

16

What is the definitive diagnosis for sickle cell anemia

Hb electrophoresis

17

Management of sickle cell anemia

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

18

GP6D Deficiency

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

19

Management of GP6D Deficiency

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

20

Pyruvate kinase deficiency

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

21

What will you see in a pyruvate kinase deficiency

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)