#Dr_Usama Hereditary Spherocytosis, G6PD & Autoimmune Hemolytic Anemia

Question 1

Treatment (Hereditary Spherocytosis)

Answer 1

1. Folic acid supplement (1 mg/day).
2. Packed red cell transfusion for severe erythroblastopenic crisis.
3. Splenectomy (for moderate to severe cases). Splenectomy should not be done before 5 years of age. Spherocytosis persists post splenectomy, but the red cell life span becomes essentially normal and complications are prevented, especially hypoplastic crises and persistent hyperbilirubinemia, which leads to gallstones. Ultrasound should be carried out before splenectomy to exclude the presence of gallstones. If present, cholecystectomy is also indicated.

Question 2

Complications (Hereditary Spherocytosis)

Answer 2

1. Hemolytic crisis: With more pronounced jaundice, precipitated by viral infection.
2. Erythroblastopenic crisis (Hypoplastic crisis): Dramatic fall in Hb level (and reticulocyte count); usually due to maturation arrest, often associated with parvovirus B19 infection.
3. Folate deficiency and superimposed megaloblastic anemia: Caused by increased red cell turnover
4. Gallstones: In about 50% of cases; increased incidence with age.
5. Complications of chronic anemia: growth retardation, heart failure and failure to thrive necessitating intermittent or chronic transfusion.
6. Hemochromatosis: Rarely.

Question 3

Hematologic and Biochemical Features (Hereditary Spherocytosis)

Answer 3

1. Anemia and Jaundice: of variable severity
2. Splenomegaly
3. Presents in newborn (50% of cases) with hyperbilirubinemia
4. MCV usually decreased; mean corpuscular hemoglobin concentration (MCHC) raised and highly suggestive of spherocytosis; RDW elevated
5. Reticulocytosis (3–15%); spherocytes and polychromasia
6. Increased red cell osmotic fragility ; occasionally only demonstrated after incubation of blood sample at 37C for 24 hours
7. Raised indirect bilirubin; obstructive jaundice may develop due to gallstones secondary to increased pigment excretion.

Question 4

Glucose-6-Phosphate Dehydrogenase Deficiency definition

Answer 4

It is a sex-linked recessive mode of inheritance disease

•It is fully expressed in hemizygous males and homozygous females, with variable intermediate expression in heterozygous females (due to random deletion of X chromosome, according to Lyon hypothesis).

•It is most frequent among African-American, Asian and Mediterranean peoples

Question 5

Glucose-6-Phosphate Dehydrogenase Deficiency Pathogenesis

Answer 5

In G6PD deficiency there is an abnormality in the hexose monophosphate shunt pathway of glycolysis and decreased glucose metabolism

•This results in the depletion of reduced nicotinamide adenine dinucleotide phosphate (NADPH) and the inability to regenerate reduced glutathione that protects RBC membrane from oxidation (drugs, infection, chemicals)

•When a patient with G6PD is exposed to significant oxidant stress, hemoglobin is oxidized, forming precipitates of sulfhemoglobin (Heinz bodies), which are visible on specially stained preparations.

•Red cell G6PD activity falls rapidly and prematurely as red cells age.

Question 6

Clinical Features G6PD

Answer 6

Episodes of hemolysis may occur by: Drugs (sulfonamides, nitrofurantoin, primaquine) , Fava bean (broad bean) ingestion or exposure to pollen from the bean’s flower (hence favism), and Infection.

• Pallor, jaundice, and dark urine.
• Favism: is an acute life-threatening hemolysis, often leading to acute renal failure.
• Infants may present with neonatal jaundice which can be severe and produce kernicterus.
• Chronic nonspherocytic hemolytic anemia: Occurs mainly with sporadic inheritance; it is variable but can be severe with transfusion dependence; there is a slight jaundice and mild splenomegaly

Question 7

Lab Features G6PD

Answer 7

early on, the hemolysis usually exceeds the ability of the bone marrow to compensate, so the reticulocyte count may be low for 3 to 4 days.

-the RBC morphology during episodes of acute hemolysis is striking. RBCs appear to have “bites” taken out of them. These are areas of absent hemoglobin that are produced by phagocytosis of Heinz bodies by splenic macrophages; as a result, the RBCs appear blistered.

-hemoglobin normal between episodes.
-enzyme level assay may be normal during the acute episode.

Question 8

Treatment G6PD

Answer 8

1. Education of families and patients in recognition of food prohibition (fava beans), drug avoidance, heightened vigilance during infection and the symptoms and signs of hemolytic crisis (orange/dark urine, lethargy, fatigue, jaundice).
2. Transfusion of packed red blood cell in children presenting with acute hemolytic anemia when Hb level below 7 g/dl, or in persistent hemoglobinuria and Hb below 9 g/dl
3. Maintain hydration and urine alkalization to protect the kidneys against damage from precipitated free hemoglobin
4. In patients with severe chronic anemia: transfuse red blood cells to maintain Hb level 8–10 g/dl and iron chelation. Splenectomy has only occasionally ameliorated severe anemia in this disease.

Question 9

Auto Immune hemolytic anemia Etiology

Answer 9

•Idiopathic
•Infections (Epstein-Barr virus, rarely HIV, cytomegalovirus, and mycoplasma)
•Immunologic diseases (systemic lupus erythematosus [SLE], rheumatoid arthritis)
•Immunodeficiency diseases (agammaglobulinemia, dysgammaglobulinemias)
• Neoplasms (lymphoma, leukemia, and Hodgkin disease)
• Drugs (methyldopa, L-dopa, penicillins, cephalosporins)

Question 10

Clinical Manifestations (Auto Immune hemolytic anemia )

Answer 10

🔴1- Acute transient type: lasting 3-6 months and occurring predominantly in children ages 2-12 yr, accounts for 70-80% of patients. It is frequently preceded by an infection, usually respiratory.
●Onset may be acute, with pallor, jaundice, fever, and hemoglobinuria, or more gradual, with primarily fatigue and pallor.
●The spleen is usually enlarged and is the primary site of destruction of immunoglobulin G (IgG)–coated RBCs.
●Underlying systemic disorders are unusual.
●Response to glucocorticoid therapy is optimal, with a low mortality rate

🔴2- Prolonged and chronic type: which is more frequent in infants and in children >12 yr old.
➢Hemolysis may continue for many months or years.
➢Abnormalities involving other blood elements
➢The response to glucocorticoids is variable and inconsistent
➢The mortality rate is approximately 10%
➢It is often attributable to an underlying systemic disease

Question 11

Auto Immune hemolytic anemia Lab finding

Answer 11

I. Anemia; Hemoglobin level—very low
II. Peripheral blood smear; prominent spherocytes, polychromasia, macrocytes, autoagglutination
III. Reticulocytosis
IV. Evidence of hemolysis: Hyperbilirubinemia, decreased haptoglobin level, hemoglobinuria, and increased urinary urobilinogen
V. Direct coomb’s test: which is positive