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45-year old man presents to GP with lethargy for the last few months; FBC…

- - - - Aplastic anemia: primary (often acquired autoimmune cause or genetic e.g. Fanconi anemia) or secondary (due to drugs e.g. chemotherapy or carbimazole, toxins, radiation etc, viruses e.g. parvovirus, hepatitis and HIV can cause transient anemia or pancytopenia); ask for relevant exposures
      - Malignant and pre-malignant e.g. bone marrow infiltration by leukemia, myeloma, myelofibrosis; look for constitutional symptoms, hepatosplenomegaly and CRAB symptoms of melanoma (hyperCa, renal impairment, anemia and bone pain)
    - - Renal disease: insufficient synthesis of erythropoetin
      - Chronic disease: inadequate erythropoesis and decreased RBC survival; chronic inflammatory states e.g. infection, RA, cancer
      - Pure RBC aplasia
      - Myelodysplastic syndrome
  - - - Non-megaloblastic
        
        Pregnancy
        
        Alcoholism
        
        Liver disease
        
        Hypothyroidism
        
        Drugs (e.g. azathioprine)
      - Megaloblastic
        
        Vitamin B12/folate deficiency: dietary deficiency e.g. vegan (no B12); folate deficiency is common in the malnourished; pernicious anemia due to autoimmune destruction of parietal cells (hence decreased intrinsic factor and Vit B12 absorption) ; PE: glossitis, vibration/proprioception loss, weakness and ataxia
        
        Drugs: methotrexate, phenytoin, trimethoprim, etc inhibit folate metabolism
        
        GIT: gastrectomy (decreased intrinsic factor production), ileal resection/disease (decreased Vit B12 absorption)
    - - Iron deficiency: physical signs of koilonychia or angular chelitis; look for causes: (1) blood loss [NSAIDs use, GIT malignancy]; (2) increased demand [pregnancy]; (3) decreased absorption (gastrectomy); (4) poor intake
      - Thalassemia: genetic defects; thalassemia minor is asymptomatic except for mild microcytic anemia
      - Sideroblastic anemia: ineffective heme synthesis, either inherited or acquired
      - Anemia of chronic disease: usually normocytic but may present as microcytic anemia as inflammation increases hepcidin and inhibits iron absorption
- - - - Defect in enzyme [G6PD deficiency]: acute hemolytic episodes, precipitated by infection, drugs (e.g. anti-malarials, antibiotics, analgesics), fava beans; blood count is normal between episodes
      - Defect in cytoskeletal e.g. hereditary spherocytosis (hepatosplenomegaly, sphereocytes on PBF, positive osmotic fragility test), elliptosis, stomatocytosis
      - Defect in hemoglobin: thalassemia or sickle cell anemia
    - - Autoimmune hemolytic anemia: most common cause, confirmed by + direct Coomb's test; look for etiology (infective, usually mycoplasma, CMV, EBC; inflammatory, any autoimmune disease; neoplastic, lymphoma or CLL, examine for nodes; microangiopathic hemolytic anemia, hemolytic picture with schistocytes and -ve Coomb's test; malaria, fever, travel hx, use of prophylaxis; fragile RBC e.g. B12 deficiency; mechanical hemolysis, e.g. prosthetic valves; hypersplenism)