Two cases of microcytic hypochromic anemias albiet not iron deficiency but iron excess
Case Report
Two cases of microcytic hypochromic anemias albiet not iron deficiency but iron excess
https://doi.org/10.21203/rs.3.rs-1444495/v1
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Two cases of microcytic hypochromic anemias albiet not iron deficiency but iron excess
dyserythropoeisis
hemolysis
sideroblastic
Iron excess or overload can be due to an increased supply for demand (multiple blood transfusions and oral intake), increased RBC breakdown (hemolytic anemia) which directly releases iron in the serum and immobilization of iron stores owing to ineffective erythropoeisis to form a vicious circle which leads to pathological iron deposition, malfunctioning and enlargement of organs. Bone marrow erythroid hyperplasia showing abundance of dysfunctional erythroblasts with insufficient reticulocytosis is the hall mark for this condition.[1] The biochemical, serological and hematological findings (indirect hyperbilirubinemia, elevated lactate dehydrogenase (LDH), decreased haptoglobin) are consistent with a hemolytic anemia. The causes can be both inherited and acquired. We present two such cases, having a microcytic hypochromic blood picture with marked anisopoikilocytosis mimicking iron deficiency anemia but not responding to iron therapy or blood transfusions. As the patients condition worsened, bone marrow examination (BME) was done to evaluate for a refractory anemia.
Case 1: A 60 year old female was admitted in the cardiology department with complaints of palpitations, hypertension and yellowish discolouration of skin. She also confirmed frequent admissions in different hospitals for management of anemia in the past since adolesecence. Laboratory investigations revealed indirect hyberbilirubinemia, microcytic hypochromic anemia (mchc), elevated LDH and polychromasia with nucleated RBCs on peripheral smear (PS).(figure 1a) Spleen (13 cm) and liver (21cm) were enlarged in size with evidence of cholelithiasis. Coomb’s test and anti nuclear antibody (ANA) by (IIF) were negative ruling out an autoimmune hemolytic anemia. There was no evidence of hemoglobinemia, hemoglobinuria or urobilinogen in urine. No abnormal hemoglobin was detected by Hb. electrophoresis. Bone marrow aspirate (BMA) smears were hypercellular for age and showed an increase in the number of late erythroblasts which revealed dyspoeisis in the form of nuclear budding, multinucleation and karyorrhexis in >10% of the erythroblasts.(figure 1b) Myeloid and megakaryocytic lineages showed normal maturation. Stores for iron were saturated. A diagnosis of Congenital dyserythropoeitic Anemia-type II (CDA-II) was suggested after a positive result on acid hemolysis test (HAM test) with recommendation for iron chelation and splenectomy.[2]
Case 2: A 47 year old male presented with difficulty in breathing, generalised weakness and fever. The hematological, biochemical and radiological findings were those of a hemolytic anemia similar to case 1. However the findings on PS and BMA were different. The polychromatic RBCs were additionally found to have granular pappenheimer bodies (siderocytes).(figure 2b) BMA smears revealed erythroid hyperplasia with presence of ringed sideroblasts on perl’s stain.(figure 2a) Serum copper levels were found to be low (50ug/dl, N=74-130ug/dl)).A diagnosis of acquired sideroblastic anemia was offered.[3, 4] The patient was supplemented with pyridoxine (vit.B6) injections and discharged with a Hb of 10g/dl.
A finding common to both the cases was their refractoriness to iron supplementation despite a peripheral smear report of mchc anemia. In contrast, the iron profile was consistent with a state of “Iron overload” which means there is a fraction of unbound iron circulating in the body along with hypersaturated transferrin and markedly high ferritin levels. In simpler words, the bone marrow cells are incapable of using iron for erythropoeisis.[5] They fail to differentiate completely and die prematurely. This is called as “intramedullary hemolysis” due to “ineffective erythropoeisis’’ and can be seen in many conditions where the heme or globin synthesis is defective. In such cases, blood transfusions and iron therapy can have deleterious consequences like end organ damage due to secondary hemochromatosis. Hence, it is important to identify them at the earliest and the clue to it is a highly staurated transferrin (TSI>45%) followed by bone marrow smear examination and perl’s stain because the erythroblast morphology is the key in diagnosis.
2)Tandon B, Peterson LC., Norwood S, Zakarija A, Chen YH. Congenital dyserythropoietic anemia type II (CDA II) diagnosed in an adult patient. J Hematopathology. 2010;3:149-53. https://doi.org/10.1007/s12308-010-0073-5.
4)Abu-Zeinah G, DeSancho MT. Understanding Sideroblastic Anemia: An Overview of Genetics, Epidemiology, Pathophysiology and Current Therapeutic Options. J Blood Med. 2020;11:305-318. doi: 10.2147/JBM.S232644.
1)Camaschella C, Nai A. Ineffective erythropoiesis and regulation of iron status in iron loading anaemias. Br J Haematol. 2016;172:512-23. doi: 10.1111/bjh.13820.
3)Bottomley SS, Fleming MD. Sideroblastic anemia: diagnosis and management. Hematol Oncol Clin North Am. 2014;4:653-70, v. doi: 10.1016/j.hoc.2014.04.008.
5)Fibach E, Rachmilewitz EA. Iron overload in hematological disorders. Presse Med. 2017;46(12 Pt 2):e296-e305
doi: 10.1016/j.lpm.2017.10.007.
Hb- hemoglobin, TLC= total leucocyte count, RBC= red blood cell count, MCV= mean corpuscular volume, MCH= mean corpuscular hemoglobin, MCHC= mean corpuscular hemoglobin concentration, RDW= red cell distribution width, T.bil= total bilirubin, D.bil=direct bilirubin, In.bil= indirect bilirubin, Plt= platelet count, LDH=lactate dehyrogenase, ALP=alkaline phosphatase, UA= uric acid, UIBC=unsaturated iron binding capacity, TIBC= total iron binding capacity, TSI=transferrin saturation index
Ethics approval statement:- This study did not require ethics approval and it was clarified during scientific review that this is a retrospective study and data would be anonymised and collected as part of routine care.
Competing interests- The authors declare that they have no competing interests
Participant consent - A verbal consent for participation was obtained from the patient with an assurance that no personal information shall be disclosed and identity shall be kept anonymous
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