Microcytic anemia

Question 1

Which infectious organism are thalassemia carriers protected against?

Answer 1

Plasmodium falciparum malaria. This is because the parasite has reduced multiplication within the RBCS while parasite invasion is intact. Additionally, this effect is much more pronounced in alpha thalassemia (think about it - in Africans more, who need this protection more!!).

Question 2

Which infectious organism are thalassemia carriers protected against?

Answer 2

Plasmodium falciparum malaria.

Question 3

Genetic defect behind alpha thalassemia

Answer 3

Gene deletion. Normally, 4 alpha genes are present on chromosome 16.

Question 4

Options if 2 alpha genes are deleted from chromosome 16

Answer 4

ild anemia with increased RBC count. Cis deletion is associated with an increased risk of severe thalassemia in offspring – seen in Asians. Trans deletion, when one deletion occurs on each chromosome, is seen in Africans.

Question 5

What happens when 3 alpha genes are deleted on chromosome 16?

Answer 5

Severe alpha thalassemia anemia- Beta chains form tetramers (HbH) that damage RBCs.

Question 6

What happens when 4 alpha genes are deleted on choromsome 16?

Answer 6

Lethal i utero (Hydrops fetalis). Gamma chains form tetramers (Hb Barts) that damage RBCs.

Question 7

Genetic defect behind beta thalassemia

Answer 7

GEne mutations (point mutations in promoter or splicing sites) – seen in African and Mediterranean individuals.

Question 8

Describe Beta thalassemia minor.

Answer 8

(B/B+); mildest, usually asymptomatic with an INCREASED RBC count. Microcytic, hypo chromic RBCs and target cels are seen on blood smear. Hb electrophoresis shows slightly decreased HbA with increased HbA2 and HbF.

Question 9

Describe B-thalassemia major

Answer 9

B0/B0 is the most severe form and presents with severe anemia a few months after birth. This is because the High HbF (a2y2) at birth is temporarily protective. Alpha tetramers aggregate and damage RBCs, resulting in ineffective erythropoiesis and extravascular hemolysis (removal of circulating RBCs by the spleen). Massive erythroid hyperplasia ensures, resulting in (1) expansion of hematopoiesis into the skull (crewcut appearance on X-ray) and facial bones (chipmunk facies), extra medullary hematopoiesis with hepatosplenomegaly, and risk of aplastic crises with parvovirus B19 infection of erythroid precursors. Chronic transfusions often lead to secondary hemochromatosis.

Question 10

Options if 2 alpha genes are deleted from chromosome 16

Answer 10

Mild anemia with increased RBC count. Cis deletion is associated with an increased risk of severe thalassemia in offspring – seen in Asians. Trans deletion, when one deletion occurs on each chromosome, is seen in Africans.

Question 11

Describe B-thalassemia major

Answer 11

B0/B0 is the most severe form and presents with severe anemia a few months after birth. This is because the High HbF (a2y2) at birth is temporarily protective. Alpha tetramers aggregate and damage RBCs, resulting in ineffective erythropoiesis and extravascular hemolysis (removal of circulating RBCs by the spleen). Massive erythroid hyperplasia ensures, resulting in (1) expansion of hematopoiesis into the skull (crewcut appearance on X-ray) and facial bones (chipmunk facies), extra medullary hematopoiesis with hepatosplenomegaly, and risk of aplastic crises with parvovirus B19 infection of erythroid precursors. Chronic transfusions often lead to secondary hemochromatosis.

Question 12

Significant infectious cause of morbidity in patients with thalassemia

Answer 12

Yersinia enterocolitica, which contains several pathways to facilitate iron uptake which is essential for this organism’s growth.