RBC disorders 1

Question 1

Anemia

Answer 1

Reduction, below normal limits, of total circulating red cell mass.

Question 2

Clinical symptoms of anemia

Answer 2

• Easy fatigability and loss of energy
• Headaches
• Fainting or dizziness
• Shortness of breath
• Palpitations
Severe anemia: Angina ,CHF , confusion

Question 3

Clinical signs of anemia

Answer 3

-Pallor
-Hemic murmurs
-Increased pulse rate and respiratory rate which can increase stroke volume and eventually (if severe) can lead to high output cardiac failure

Question 4

Anemia can be classified based on:

Answer 4

1) The morphological changes in RBCs
2) The pathophysiological mechanisms causing the anemia

Question 5

Morphological Classification of Anemia

Answer 5

-Normochromic/hypochromic
-macrocytic/normocytic/microcytic
-based on cell shape

Question 6

Microcytic Hypochromic anemias

Answer 6

-iron deficiency
-anemia of chronic disease
-lead poisoning
-thalassemia

Question 7

Normochromic Normocytic anemia

Answer 7

-acute blood cell
-hemolytic anemia
-anemia of chronic disease

Question 8

Normochromic Macrocytic anemia

Answer 8

-folate deficiency
-B12 deficiency

Question 9

Classification of Anemia According to Underlying Mechanism

Answer 9

-accelerated RBC loss / destruction
-impaired RBC production

Question 10

What is the immediate concern with anemia caused by acute bleeding

Answer 10

Hypovolemia
-it is a normocytic normochromic anemia

Question 11

Anemia caused by chronic blood loss

Answer 11

-Rate of loss > RBC regeneration
-iron stores are gradually depleted
-no risk of hypovolemia
-microcytic hypochromic anemia

Question 12

Hemolytic anemias common features

Answer 12

• Shortened RBC life span( below 120 days) - Increase in erythropoietin & erythropoiesis - Accumulation of Hb breakdown products

Question 13

Classification of hemolytic anemias

Answer 13

1) By site: intravascular or extravascular
2) By cause: intrinsic or extrinsic (to RBCs)

Question 14

Intravascular Hemolysis:

Answer 14

-Mechanical injury to RBCs
-complement fixation
-infections
-no organomegaly

Question 15

Extravascular Hemolysis

Answer 15

– Caused by defects that increase the destruction of RBCs by the phagocytes in the spleen
• RBCs rendered “less deformable”
• RBCs rendered “foreign” usually by immune
mechanism (antibody coating)
– Associated with Splenomegaly

Question 16

Laboratory Evidence of Hemolytic Anemia- peripheral blood

Answer 16

– Normochromic normocytic anemia, with polychromasia ±
nucleated RBCs.

Question 17

Laboratory Evidence of Hemolytic Anemia-bone marrow

Answer 17

– Show erythroid hyperplasia leads to RBC
production(↑Reticulocytes)

Question 18

Laboratory Evidence of Hemolytic Anemia-Plasma/serum: RBC breakdown

Answer 18

-Increased Bilirubin (unconjugated )
-increased LDH
-absent haltoglobin
-increased free Hb (intravascular )
-, Hemoglobinuria (intravascular hemolysis/ negative in extravascular )

Question 19

Intrinsic RBC Defects

Answer 19

-hereditary

– Membrane defect: Hereditary Spherocytosis
– Enzyme defect: G-6-PD deficiency, Paroxysmal nocturnal hemoglobinuria (PNH) – Acquired
– Hemoglobin defect: Sickle cell disease, Thalassemi

Question 20

Extrinsic Defects

Answer 20

-Acquired

– Immune mediated damage: autoimmune diseases,drugs-associated, transfusion reaction.
– Nonimmune damage: mechanical trauma, infections,chemicals, hypersplenism

Question 21

Hereditary Spherocytosis

Answer 21

• inherited abnormalities in critical proteins in the RBC membrane skeleton
  • The RBCs become spheroid in shape, less deformable, and are destroyed in the spleen
  • Average RBC lifespan is10-20 days

Question 22

What proteins are affected in hereditary spherocytosis

Answer 22

-ankyrin , band 3 , spectrin and band 4.2

Question 23

Pathogenesis of Hereditary Spherocytosis(extravascular)

Answer 23

Reduced RBC membrane stability→loss of small fragments during normal shearing stresses in the blood circulation→RBCs become increasingly more spherical→unable to traverse the splenic sinusoids→phagocytosis and destruction by splenic macrophages (spleen usually enlarged)

Question 24

Hereditary Spherocytosis: Clinical Features

Answer 24

-Anemia
-splenomegaly
-jaundice

Question 25

Hereditary Spherocytosis: Diagnosis and Lab Findings

Answer 25

-family evidence -hemolysis -Normochromicnormocyticanemia • Spherocytes • Polychromaticcells±nucleated RBCs • Howell-Jolly bodies -increase in MCHC

Question 26

Osmotic fragility test for hereditary spherocytosis

Answer 26

– This test confirm the presence of spherocytes – Spherocytic RBCs lyse prematurely (compared to normal RBCs), when exposed to increasingly hypotonic salt solutions

Question 27

Coombs test fir hereditary spherocytosis

Answer 27

– Spherocytes can also be seen – Autoimmune hemolytic anemias(+ve coombs test) – A Negative Coombs test will confirm the diagnosis of Hereditary spherocytosis

Question 28

G6PD A- variant:

Answer 28

– Present in ~ 10% of the American Blacks – Characterized by normal enzyme activity but a decreased half-life

Question 29

G6PD Mediterranean variant

Answer 29

– Mostly seen in Middle Eastern populations – Thought to be due to natural selection -half live severely reduced

Question 30

G6PD Deficiency: Pathophysiology

Answer 30

-Abnormal enzyme variants are misfolded and are thus susceptible to proteolytic degradation -mature RBCs have no nucleus -enzyme activity is decreased -Heinz bodies (intravascular) -bite cells (extravascular)

Question 31

How are Heinz bodies formed

Answer 31

G6PD deficient RBCs, exposed to a high level of oxidants→oxidation of sulfhydryl groups (SH groups) on globin chains of Hb→denatured and formed membrane bound precipitate

Question 32

How are bite cells foremen

Answer 32

If membrane damage is severe, intravascular hemolysis occurs. Less affected RBCs traverse the spleen where macrophages “bite” out the inclusions→bite cells. -These abnormal RBCs are eventually removed by the spleen (extravascular hemolysis)

Question 33

G6PD Deficiency: Clinical Presentation

Answer 33

-G6PD deficiency is an X-linked recessive disorder (mostly affect Males) -neonatal jaundice -Chronic low-grade hemolytic anemia

Question 34

G6PD Deficiency: Diagnosis and Lab Findings

Answer 34

+/- Hemoglobinemia,& Hemoglobinuria ↑Reticulocytes, -LDH, -Free Hb -Absent Haptoglobin