Haematology Watch

 Haematology Watch, Vol.4 , Issue 1.


The Forgotten Mechanism in beta-Thalassaemia major

Abdulsalam Abbas Hashim

Ineffective erythropoiesis in β-thalassemia major: 

In general, red cell hemolysis or shortened survival can be largely compensated by effective bone marrow hyperplasia which in turn results in marked peripheral reticulocytosis that can parallel the level of anemia unless a co-morbid nutritional anemia or ineffective erythropoiesis exist which in turn limits the ability of bone marrow response. 

However, in β-thalassemia major, which is one form of hemolytic anemia, anemia results primarily from reduced and defective hemoglobin production. The presence of defective hemoglobin (excess of α-globin chains (1) that are highly unstable and precipitate in red cells precursors and progeny forming intracellular inclusions) in turn results in extravascular (producing splenomegaly) and intravascular (resulting in iron deposition in various body organs) hemolysis, and ineffective erythropoiesis (a mechanism that is crucial but usually much less appreciated). The level of reticulocytosis in this form of hemolytic anemia can vary in keeping with the degree of ineffective erythropoiesis. 

These images are from a 3 years old female with regular transfusion-dependant anemia since age of 3 months. 

Hb 9.4 g/dl, WBC 5.0 * 109/l, Platelets 266 * 109/l 

PB film revealed essentially a normchromic normocytic anemia with a smaller population of hypochromic microcytes. WBC and platelets are normal. 

Hb electrophoresis was not performed before starting repeated blood transfusion due to the fact that this girl’s family is living in a poor rural area with no access to most of the diagnostic facilities. At presentation, the electrophoresis was unremarkable apart from mildly elevated HbF (4.1 %). However, this result should not be considered valid due to the fact of repeated blood transfusion. 

There was a marked reticulocytopenia, less than 0.1 % (Figure 1). 


Her pediatrician suspected the diagnosis to be a congenital pure red cell aplasia (although absence of peripheral blood macrocytosis at this age is against the diagnosis) and asked for a bone marrow study. 

The bone marrow was hypercellular with marked erythroid hyperplasia and smear cells and a typical picture of β-thalassemia major including alpha chain inclusions with defective hemoglobinization and dyserythropoiesis (Figure 2) (1). 


Many iron-laden macrophages are seen (Figure 3). 


This probably results from the repeated blood transfusion without iron chelation. Ineffective erythropoiesis is a contributing factor. 

Conclusion: The presence of both marked bone marrow erythroid hyperplasia with peripheral blood reticulocytopenia is a typical representation of ineffective erythropoiesis. 


N.B.: “A written informed consent was obtained from the patient”. 



1. Abdulsalam A., Sabeeh H., Bain B. 2011. Diagnosis of beta thalassemia major from bone marrow morphology. American Journal of Hematology; 86 (2): 187.