In patients with thalassemia, the extent of ineffective erythropoiesis
also determines iron distribution.
For example, the rapid apoptosis and ineffective erythropoiesis
may appear due to the oxidative damage to the red blood cells (RBCs) in thalassaemic patients.
Programmed cell death (PCD) and ineffective erythropoiesis
in Cooley's anemia," Blood, vol.
The disease leads to ineffective erythropoiesis
, severe anemia, bone marrow expansion, skeletal deformity, increased gastrointestinal iron absorption and the patient requires regular blood transfusion and iron-chelating therapy throughout life from early childhood (1-3).
The consequences of ineffective erythropoiesis
on hepcidin expression thus appear to trump the consequences of excessive iron stores.
LDH examined in conjunction with the known normal bilirubin level would further rule out anemia due to accelerated red cell death either in the peripheral blood as in hemolysis or within the marrow where maturation defects result in ineffective erythropoiesis
, as in megaloblastic anemia and thalassaemia.
Anaemia in falciparum malaria is clearly multifactorial and there is a strong argument that erythrocyte destruction and ineffective erythropoiesis
play equal parts in the etiology of malarial anaemia.
Myelodysplastic syndromes (MDS) are a heterogeneous group of hematologic malignancies of the bone marrow commonly leading to severe and chronic anemia due to ineffective erythropoiesis
(red blood cell formation).
6] and maintaining the circulating level of haemoglobin (Hb) sufficient to suppress endogenous ineffective erythropoiesis
It is thought to result from a combination of hemolysis of parasitized red blood cells, accelerated removal of both parasitized and innocently unparasitized red blood cells, depressed and ineffective erythropoiesis
with dyserythropoietic changes, and anemia of chronic disease.
This leads to excessive accumulation of alpha chains, which precipitate and cause lipid peroxidation of red cell membrane leading to haemolysis, ineffective erythropoiesis
and severe anaemia.
Nevertheless, ineffective erythropoiesis
was described in studies of the bone marrow of patients with anaemia as well as malaria (10).
When anemia is accompanied by increased erythroid activity and/or ineffective erythropoiesis
We are very excited by these new data with ALN-TMP where we have demonstrated disease modifying effects in models of -thalassemia, including amelioration of anemia, iron overload, extra-medullary hematopoiesis, and ineffective erythropoiesis
, in addition to correction of globin gene expression.
, apoptosis, and oxidative damage are central components of the disease and its shortened red cell survival.