RBC disorders 2

Question 1

Sickle Cell Disease

Answer 1

HbA is completely replaced by HbS, due to a point mutation at position 6 in the β globin gene→ glutamic acid replaced by valine→HbS

Question 2

Things that decrease sickling

Answer 2

– Presence of HbA in HbAS
– Presence of Hb
– Coexistence of α-thalassemia decreases the Hb concentration

Question 3

• Crises are usually precipitated by

Answer 3

– Infections
– Dehydration
– Exposure to cold – Hypoxia
– Acidosis
(Presence of HbC increases sickling)

Question 4

Sickle cell disease : clinical features

Answer 4

-chronic hemolysis intravascular and extravascular hemolysis
-moderate to severe anemia
-Bone marrow becomes hyperplastic
-entrapment of sickled cells
-Hb degradation causes hyperbilirubinemia and eventually causes gallstones

Question 5

What are changes that happen with hyperplastic bone marrow

Answer 5

-Changes In the bony skull
-prominent cheek bones in children
-Skull x-ray crew cut appearance (which is hair on end appearance due to elongated trabeculae)

Question 6

What does entrapment of sickle cells in the spleen cause

Answer 6

-splenomegaly in children
-repeated infarctions and fibrosis lead to autosplenectomy by early adulthood patients become more prone to infections


Question 7

At what age do patients with sickle cell become symptomatic

Answer 7

Patients are usually asymptomatic until six months of age when the shift from HbF to HbS is complete

Question 8

Vaso-occlusive /painful crisis

Answer 8

B-ischemic events due to microvascular occlusions with pain and can lead to significant morbidity and mortality commonly seen in children
Affects different organs producing different manifestations affects your bones lungs brain retina kidneys penis leg ulcers 

Question 9

Sequestration crises

Answer 9

– Occur in children with intact spleens
-Massive entrapment of sickle are red blood cells needs to rapid pooling of blood in the spleen causing splenomegaly and autosplenectomy

Question 10

Aplastic crises

Answer 10

– Red cell progenitors are infected by parovirus B 19
-causes a transient cessation of erythropoiesis and a sudden worsening of the anemia
– Self limited

Question 11

Hemolytic crisis

Answer 11

– Exaggeration of the Hemo lysis

Question 12

Sickle cell disease diagnosis and lab findings

Answer 12

-family history, evidence of hemolysis
– Sickle cells
– polychromatic cells (reticulocytes released prematurely by BM to compensate for loss of red blood cells])
-Howell -Jolly bodies

Question 13

What is the confirmatory test for sickle cell

Answer 13

HBelectrophoresis
– sickle cell anemia: HbS ,HbF and no HbA
-sickle cell trait : HbS ,HbF and HbA

Question 14

Sickle cell treatment

Answer 14

– Rehydration ,analgesics, exchange transfusions
-Folic acid supplementation
– penicillin prophylaxis
– hydroxyurea [increases the amount of HBF in red blood cells and inhibits polymerization us HBS]
-bone marrow transplantation

Question 15

Thalassemia Syndromes

Answer 15

-decreased synthesis of α- or β-globin chains, leading to:

– Low levels of normal Hb (hypochromic microcytic RBCs)
– Red cell damage, due to the relative excess of the unimpaired normal chains→aggregates→insoluble inclusions→extravascular hemolysis

Question 16

β-Thalassemia

Answer 16

-Diminished synthesis of structurally normal β-globin chains, with unimpaired α-chain production

Question 17

β-Thalassemia Major: Thalassemia Major Syndrome Pathogenesis

Answer 17

• The reduced β-globin synthesis causes impaired Hb
production leading to hypochromic microcytic anemia
• The relative excess of α-globin chains can precipitate and cause reduced survival of RBCs & RBC precursors, due to cell membrane damage.

Question 18

β-Thalassemia Major: Clinicopathological features

Answer 18

-huge spleen and liver
-ineffective erythropoiesis
-expansion of hematopoietic marrow
-excessive dietary iron absorption and regular blood transfusions (which causes iron overload (hemosiderosis or 2o hemochromatosis) affecting the heart, liver, skin and pancreas)

Question 19

ꞵ-Thalassemia (Extravascular)- hemolysis investigations

Answer 19

↓Haptoglobin
↑Reticulocytes, LDH, Free Hb
Unconjugated bilirubin

Question 20

Major B Thalassemia specific investigations

Answer 20

-HbElectrophoresis: Reduction or absent HbA
↑HbF and
HbA2( N, ↑ or ↓)

Question 21

Minor B thalassemia investigations

Answer 21

Hb Electrophoresis ↓HbA, ↑HbA2, HbF(N or ↑)
PB: hypochromic, microcytic anemia

Question 22

Complications of B thalassemia

Answer 22

• Growth retardation and death, unless given regular blood transfusions
• Cardiac failure can occur due to:
– Severe anemia (high output failure)
– Iron overload→cardiomyopathy (important cause of death)
• Iron chelators to prevent overload

Question 23

α Thalassemia (Extravascular) - Pathogenesis

Answer 23

Deletion of one or more α-chain globin

Question 24

The clinical syndromes of a thalassemia

Answer 24

• α-Thalassemia minima (Silent Carrier): – 1 α-gene is deleted (α/α,α/-)
• α-Thalassemia minor/trait: 2 α-genes deleted
• Hemoglobin H disease: 3 α-genes deleted (α/-,-/-)
• Hemoglobin Barts: All the 4 α-genes are deleted (-/-,-/-)

Question 25

Hemoglobin H disease

Answer 25

– Both HbA and HbH are produced
– HbH is formed from tetramers of excess β-globin chains
– HbH has high affinity for O2, leading to severe tissue
hypoxia
– HbH is prone to oxidation → precipitated inclusions in older
RBCs→extravascular hemolysis→moderate anemia

Question 26

Hemoglobin Barts (Hydrops Fetalis)

Answer 26

-Not compatible with life
-can’t produce HbF
-The fetus is pale, edematous, with massively enlarged liver and spleen (Hydrops Fetalis)

Question 27

α Thalassemia (Extravascular) - lab investigations

Answer 27

↑Reticulocytes, LDH, Free Hb
Absent Haptoglobin
PB : microcytic hypochromic

Question 28

Paroxysmal nocturnal hemoglobinuria (Intravascular) - clinical features

Answer 28

• Features of anemia
• No splenomegaly
• Hemolysis (Jaundice)
-thrombosis (platelet dysfunction)

Question 29

Paroxysmal nocturnal hemoglobinuria (Intravascular)- Pathogenesis

Answer 29

Mutation of PIGA enzyme leads to def of GPI-linked protein(CD55, CD59,C8)

Question 30

Paroxysmal nocturnal hemoglobinuria (Intravascular)-Hemolysis investigations and specific investigations

Answer 30

-Hemoglobinemia,& Hemoglobinuria ↑Reticulocytes, LDH, Free Hb Absent Haptoglobin
-Flow cytometry(CD55, CD59, C8 Absence)

Question 31

Paroxysmal Nocturnal Hemoglobinuria
Associated conditions

Answer 31

-Thrombosis
-Iron Deficiency
-AML (Acute myeloid Leukemia) & MDS (Myelodysplastic syndrome
-Aplastic Anemia