Normocytic Anemia

Bleeding

• Recent or Chronic?
• Common sites: GI, GU, Pulm, Psoas
• Iatrogenic?

Hemolytic Anemias

• Microangiopathic
• Artificial valves or surfaces, tight coarcts, HUS, TTP, DIC, Severe GN, mitomycin C, CSA
• Abnormal morphology:


Hemolytic anemias

• Immune Mediated
• Warm antibodies:  rule out lymphoproliferative disease, connective tissue disease, and drugs (positive Coombs, often with spherocytes).
• Cold agglutinin: rule out mycoplasma, EBV, lymphoproliferative disorders
• Paroxysmal Cold Hemaglobinuria:  Especially with acute/severe hemolysis and hemoglobinuria.  Check Donath-Landsteiner antibody (anti-P antibody)
• Neonatal isoimmune: Rh(D), ABO, minor antigens (C,c,E,e,Kell, Duffy, Kidd, M, N, S, s)
• Transfusion reactions (especially delayed reactions)
• Toxins
• Drugs, water (fresh water drowning), Copper (Wilson's disease, esp 4-30 years, LFTs increased; no specific morphology, check Cu, ceruloplasmin, slit lamp exam)
• Infections
• Malaria, babezia (Cape Cod, N.E. Islands), Clostridia (4+ spherocytes, intravenous lysis)
• Mechanical/Thermal
• March hemoglobinuria, ECMO, CP bypass, blood warmers, burns
• Hypersplenism
• Hemophagocytic Syndromes
• Membrane Disorders
• congenital, dominant: Hereditary spherocytosis, hereditary elliptocytosis, hereditary pyropoikilocytosis (marked fragmentation, decreased MCV), Hereditary stomatocytosis (Increased RBC Na and K), Hereditary xerocytosis (targets, decreased RBC Na and K)
• Paroxysmal noctural hemoglobinuria (PNH)
• Rare antigen deficiencies: Rh null, In (Lu) or McLeod syndrome
• Lipid defects: spur cell anemia, LCAT deficiency, abetalipoproteinemia, high PC hemolytic anemia, vitamin E deficiency
• Hemoglobin disorders
• unstable hemoglobins (eg, Hgb E)
• Hb S, C, D
• Metabolic disorders
• Glycolytic enzyme defects: hexokinase, GPI, PFK, TPI, PGK (x-linked), PK
• Nucleotide metabolism defects: pyrimidine-5'-nucleotidase, adenylate kinase, ADA excess
• Oxidant sensitivity: G6PD, GSH synthesis defects, severe hypophosphatemia (RBC ATP deficiency)

Hypoplastic/Dysplastic Bone Marrow

• Aplastic anemias (nonspecific morphology, normal bilirubin, low to normal reticulocytes)
• Fanconi's
• Schwachman-Diamond (pancreatic insufficiency, various cytopenias, FTT +/- metaphyseal dysostosis)
• Aplastic anemia (radiation, drugs, EtOH, EBV, hepatitis, pregnancy, autoimmune)
• Preleukemia (rare in children)
• PNH
• Myelophthisis (nucleated RBCs, tear drops, early WBCs, mega fragments)
• Leukemia, lymphoma
• Histiocytosis syndromes
• Metastatic tumors (especially neuroblastoma, rhabdomyosarcoma)
• Granulomas
• Advanced storage diseases
• Myelofibrosis
• Osteopetrosis
• Myelodysplastic syndromes
• HIV infection

Erythroid Aplasia/Hypoplasia

• Pure RBC aplasia
• TEC
• Aplastic crisis (parvovirus; giant pronormoblasts) in patients with chronic hemolytic anemias (abnormal morphology, follow reticulocyte count and smear after acute crisis).
• Chronic parvovirus infection with immune compromise (treat with IVIG)
• Thymoma
• Renal Disease
• Liver Disease
• Endocrine Disease
• Hypothyroidism
• Hypopituitarism
• Anemia of chronic disease
• Early Fe deficiency

Dysplasia: ineffective erythropoesis

• HEMPAS (nonspecific morphology, bone marrow more than 10% binucleate late erythroblasts, positive Ham test, negative sugar-water test)
• Other CDAs

Work-up (selectively):

Guaiac stool, vomit, etc., add up all lab draws.

Smear, BUN, Heinz body prep, Coombs, sickle prep, hemoglobin electrophoresis, hemoglobin heat stability and isopropyl stability, incubated osmotic fragility, sugar water test, RBC enzyme panel, ceruloplasmin and copper, HAMS test, spectrin quantitation, cation permeability

• Smear, creatinine, LFTs, TFTs, bone marrow with iron stain