RBC disorders 2 Flashcards
Sickle Cell Disease
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
Things that decrease sickling
– Presence of HbA in HbAS
– Presence of Hb
– Coexistence of α-thalassemia decreases the Hb concentration
• Crises are usually precipitated by
– Infections
– Dehydration
– Exposure to cold – Hypoxia
– Acidosis
(Presence of HbC increases sickling)
Sickle cell disease : clinical features
-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
What are changes that happen with hyperplastic bone marrow
-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)
What does entrapment of sickle cells in the spleen cause
-splenomegaly in children
-repeated infarctions and fibrosis lead to autosplenectomy by early adulthood patients become more prone to infections

At what age do patients with sickle cell become symptomatic
Patients are usually asymptomatic until six months of age when the shift from HbF to HbS is complete
Vaso-occlusive /painful crisis
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 
Sequestration crises
– 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
Aplastic crises
– Red cell progenitors are infected by parovirus B 19
-causes a transient cessation of erythropoiesis and a sudden worsening of the anemia
– Self limited
Hemolytic crisis
– Exaggeration of the Hemo lysis
Sickle cell disease diagnosis and lab findings
-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
What is the confirmatory test for sickle cell
HBelectrophoresis
– sickle cell anemia: HbS ,HbF and no HbA
-sickle cell trait : HbS ,HbF and HbA
Sickle cell treatment
– 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
Thalassemia Syndromes
-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
β-Thalassemia
-Diminished synthesis of structurally normal β-globin chains, with unimpaired α-chain production
β-Thalassemia Major: Thalassemia Major Syndrome Pathogenesis
• 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.
β-Thalassemia Major: Clinicopathological features
-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)
ꞵ-Thalassemia (Extravascular)- hemolysis investigations
↓Haptoglobin
↑Reticulocytes, LDH, Free Hb
Unconjugated bilirubin
Major B Thalassemia specific investigations
-HbElectrophoresis: Reduction or absent HbA
↑HbF and
HbA2( N, ↑ or ↓)
Minor B thalassemia investigations
Hb Electrophoresis ↓HbA, ↑HbA2, HbF(N or ↑)
PB: hypochromic, microcytic anemia
Complications of B thalassemia
• 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
α Thalassemia (Extravascular) - Pathogenesis
Deletion of one or more α-chain globin
The clinical syndromes of a thalassemia
• 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 (-/-,-/-)
Hemoglobin H disease
– 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
Hemoglobin Barts (Hydrops Fetalis)
-Not compatible with life
-can’t produce HbF
-The fetus is pale, edematous, with massively enlarged liver and spleen (Hydrops Fetalis)
α Thalassemia (Extravascular) - lab investigations
↑Reticulocytes, LDH, Free Hb
Absent Haptoglobin
PB : microcytic hypochromic
Paroxysmal nocturnal hemoglobinuria (Intravascular) - clinical features
• Features of anemia
• No splenomegaly
• Hemolysis (Jaundice)
-thrombosis (platelet dysfunction)
Paroxysmal nocturnal hemoglobinuria (Intravascular)- Pathogenesis
Mutation of PIGA enzyme leads to def of GPI-linked protein(CD55, CD59,C8)
Paroxysmal nocturnal hemoglobinuria (Intravascular)-Hemolysis investigations and specific investigations
-Hemoglobinemia,& Hemoglobinuria ↑Reticulocytes, LDH, Free Hb Absent Haptoglobin
-Flow cytometry(CD55, CD59, C8 Absence)
Paroxysmal Nocturnal Hemoglobinuria
Associated conditions
-Thrombosis
-Iron Deficiency
-AML (Acute myeloid Leukemia) & MDS (Myelodysplastic syndrome
-Aplastic Anemia
