Dysplasia and Disorder of Cell Membrane Entirety in Iron-Deficiency Anemia

Abstract

Peripheral blood smears of 43 patients (26 males, median age 18 months, range: 6-180 months) with nutritional iron-deficiency anemia (IDA) were examined for the presence of trilineage hematological dysplasia. Twelve patients were reexamined for dysplastic findings after achieving a normal Hb and hematocrit level for age by the end of 2-3 months of iron treatment. A control group of 17 age-matched healthy children were also included. Neutrophils with loss of membrane entirety and protrusions were remarkable in 34/43 (79%) in the IDA group versus 1/12 (8%) after iron treatment and none of the control group. Microspherocytes were seen in 9/43 (21%) of IDA patients. Additionally, trilienage dysplasia was observed in the bone marrow samples available in 3 of the patients. It has been shown that iron-deficiency results in cellular DNA and RNA alterations, cell-cycle G1/S phase arrest, and apoptosis. Rac GTPases have been shown to control actin cytoskeleton, influencing cell polarity, microtubule dynamics, and the cytoskeletal organization of hematopoietic cells. Thus, the findings described above in neutrophils and red cells suggest a plausible link between iron and the Rac GTPase gene family. It may be a new avenue for iron waiting for proof.

Disorders Mimicking Myelodysplastic Syndrome and Difficulties in its Diagnosis

“…Trilineage dysplasia in peripheric blood of iron deficient patients were reported, being higher than the control group. In addition, microspherocytes which were observed in 20% of irondeficient patients were not noted in the control group [36]. Leukopenia and thrombocytopenia may accompanied these changes as iron deficiency deepened, making the differential diagnosis between iron deficiency anemia and MDS more difficult.…”

“…On the other hand, myelodysplastic findings in blood cells arise due to any challenge during the course of normal differentiation and therefore these changes can be encountered not only in clonal disorders like MDS (primary myelodysplasia), but also in various nonclonal disorders affecting bone marrow like viral, bacterial, parasitic infections [17][18][19][20][21][22][23][24][25][26][27], autoimmune disorders (juvenile rheumatoid arthritis, polyarteritis nodosa, systemic lupus erythematosis, immune thrombocytopenic purpura) [17,[28][29][30][31][32], hemophagocytic histiocytosis (HLH), nutritional problems (malnutrition, iron deficiency anemia, megaloblastic anemia, copper deficiency, vitamin D deficiency, hyper vitaminosis A) [27,[33][34][35][36][37][38][39][40][41][42][43], neutropenia (congenital dysgranulopoietic, congenital severe, idiopathic) [32,44,45], inherited disorders [27,46,47], malign lymphoma [48], due to effects of drugs and toxins [17,27,[49][50][51][52]…”

“…Presence of microspherocytes was attributed to a putative involvement of Rac1 and Rac2 GTPase, also known as Ras-related C3 botulinum toxin substrates 1 and 2 GTPase deficiency which reportedly altered actin assembly in red cells in mice. Further factors like cellular metabolic enzyme changes, cell growth and differentiation, and gene expression regulation might have been involved in the pathogenesis [36].…”