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Macrocytosis Vitamin B12 Folic acid Megaloblastic changes Pernicious anemia Schilling test Hypersegmented PMN. Bone marrow analysis WBC precursors Liver disease Polycythemia and erythremia PV Newborn CBC. Week 4: Macrocytic Anemia. Bone Marrow Analysis. Aspirate
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Macrocytosis Vitamin B12 Folic acid Megaloblastic changes Pernicious anemia Schilling test Hypersegmented PMN Bone marrow analysis WBC precursors Liver disease Polycythemia and erythremia PV Newborn CBC Week 4: Macrocytic Anemia
Bone Marrow Analysis • Aspirate • Particles in fluid part of marrow • Differential count • Biopsy • Solid part of the marrow • Cellularity • Clot section
Aspiration Biopsy
WBC Precursors • Myeloblast • Promyelocyte • Primary azurophilic granules • Meylocyte • Specific granules • Metamyelocyte • Band, stab • Segmented neutrophil, PMN
Myeloblast Promyelocyte Neutrophilic Myelocyte
Segmented neutrophil and lymphocyte
Mast cell and histiocyte Megakaryocyte Plasma cell Mast cell
Histiocyte Fat cell Macrophage
Osteoclasts Osteoblasts Giant cell
Non-Megaloblastic Macrocytosis • Alcoholism • Poor nutrition • Cirrhosis • Liver disease • Reticulocytosis • Hemolytic anemia • Hemorrhage
Megaloblastic Anemia • Hemolytic changes • Waxy pallor • Neurologic changes with B12 deficiency • Glossitis, beefy red or smooth pale tongue
Causes of Megaloblastic Anemia • Folate deficiency • Dietary (green leafy vegetables) • Malabsorption • B12 deficiency • Dietary • Fish tapeworm (D latum) • Pernicious anemia • Lack of gastric intrinsic factor (IF) for absorption
B12 Metabolism • Bind to cobalophilin (cobalamine binding protein) in saliva and gastric secretion • Bind to IF (from parietal cell) in the duodenum • Cbl-IF complex bind to receptor (cubilin) at distal ileum for mucosal absorption • 1% B12 can be absorbed without IF (megadose of B12 for IF deficiency, no need for IV)
MCV up to 140 fL Howell-Jolly bodies and Cabot rings Hypersegmented PMN Pancytopenia BM with low M:E ratio Megaloblastic morphology (giant bands and metas) B12 and folate assays RBC folate (long term indicator) IF antibody (PA) Schilling test (obsolete) Megaloblastic Lab Changes
Hypersegmented PMN Megaloblastic anemia Megaloblastic BM
Other Apparent Macrocytoses • Cold agglutinin • Prewarm samples • Hyperglycemia • Osmotic changes • Clot • Rouleaux
Polycythemia Vera • A type of myeloproliferative disorder (MPD) • Independent of EPO • High total RBC mass (by radio tagging)
Secondary Polycythemia • Dehydration (decreased plasma volume) • Increased O2 demand (e.g., emphysema, high elevation) • High EPO (e.g., kidney tumor)