Earliest manifestation of megaloblastic anemia is

(Ref: Harrison 18/e p866, 17/e p645-646, Tejinder Singh 2/e p54-61)   Peripheral blood picture Bone marrow picture Macrocytosis (↑ MCV, MCH. Normal MCHC) Peripheral smear            Macroovalocytes            Few nucleated RBCs            Evidence of dyserythropoiesis like- Basophilic stippling Cabot ring Howell- Jolly bodies ↓ Hb ↓ Hematocrit Reticulocyte count – Normal or mild decrease White cells- Leucopenia Hypersegmented neutrophils/ Macropolycytes- First manifestation ↓ Platelets Pancytopenia (10-20%)    Lab investigations: Serum iron, ferritin - ↑ in pure VitB12/ Folate defect Serum bilirubin & LDH ↑- due to hemolytic component Schillings test: Used to assess status of intrinsic factor (IF) & Vit B12 to distinguish pernicious anemia from other causes of Vit.B12  deficiency. Moderate- marked hypercellularity Erythroid hyperplasia M:E ratio reversal Erthropoiesis- Megaloblastic Giant metamyelocytes Mildly reduced megakaryocytes BM iron moderately increased in pure Vit B12/ Folate defects.