- Microcytic (MCV < 80) àIron-deficiency anemia, sideroblastic anemia,
anemia of chronic disease, lead poisoning, thalassemia - Normocytic (MCV 80-100) àaplastic anemia, anemia of chronic disease,
myelofibrosis/bone marrow infiltration, chronic renal failure, hemolytic anemia,
early stages of iron-deficiency anemia, hemorrhage - Macrocytic (MCV > 100) àmegaloblastic anemia (vitamin B12 and/or folate
deficiency; drug-induced), liver disease, myelodysplasia, reticulocytosis
• Clinical features àfatigue, malaise, weakness, poor exercise tolerance,
tachycardia/palpitations, dyspnea on exertion, dizziness/syncope, chest pain, pallor,
systolic ejection murmur, wide pulse pressure, orthostatic hypotension
• Presentation depends on: - Degree of anemia
- Rapidity of onset of anemia
- Age/health status
• Best initial diagnostic tests àCBC with RBC indices (e.g. MCV), reticulocyte count,
blood smear
• Management àetiology-dependent ± packed RBC transfusion
• Indications for RBC transfusion à - Acute blood loss > 30% (> 1500-2000 ml)
- Hb < 7 g/dL
- Hb < 8 g/dL (Hct < 26) + age > 65, cardiovascular/pulmonary disease and/or
acute bleed - Overtly symptomatic (e.g. chest pain, respiratory distress, CNS symptoms/signs)
Microcytic Anemia
Iron-deficiency Anemia
• Most common cause of anemia
• Females > Males
• Etiology: - Chronic blood loss àmost common cause; e.g. GI cancer, PUD, menorrhagia
- ↓ dietary intake/malabsorption à e.g. celiac disease, post-gastrectomy, cow’s
milk diet in infants, achlorhydria - ↑ requirements àe.g. pregnancy, growth spurt
- Chronic intravascular hemolysis à hemoglobinuria, hemosiderinuria
• Promoters of iron absorption à ↓ gastric pH and ascorbic acid
• Clinical features specific for iron-deficiency anemia à - brittle nails/koilonychia (spoon-shaped nails)
2 - glossitis/angular cheilitis
- pica (craving for non-nutritive substances)
- dysphagia (Plummer-Vinson syndrome)
• Initial lab results (CBC, reticulocyte count, etc.) àlow Hb and/or Hct, low MCV, ↑
RDW (red blood cell distribution width), ↓ reticulocyte count, possible thrombocytosis
• Blood smear àhypochromic, microcytic RBCs ± poikilocytosis (abnormal shapes)
• Best next step à perform iron studies: - ↓ serum ferritin àmost specific laboratory test; lacks sensitivity (falsely
elevated in inflammatory conditions, liver disease and/or malignancies) - ↓ serum iron
- ↑ TIBC (total iron binding capacity)
- ↓ transferrin saturation (serum iron/TIBC ratio, expressed as %)
• Most accurate diagnostic test àbone marrow biopsy + Prussian blue stain
• Best next step in men > 50 and/or postmenopausal women àcolonoscopy to rule out
colon cancer
• Management: - Treatment/correction of any underlying abnormality
- Packed RBC transfusion, when indicated (see above)
- PO ferrous sulfate (or ferrous gluconate) replacement àcontinued until serum
ferritin becomes normal, indicating replenishment of iron stores (~ 3-12 months) - Parenteral iron replacement, if malabsorption/intolerance to oral medications
• Adequate iron replacement indicated by à - Reticulocytosis after ~ 1 week
- Rise in Hb of ~ 1g/week
- Normalization of Hb after ~ 1 month
Anemia of Chronic Disease
• Anemia that accompanies any chronic inflammatory (e.g. RA, IBD, etc.), infectious
(e.g. TB, bacterial endocarditis, etc.) and/or malignant condition
• Pathophysiology à - ↓ sensitivity to erythropoietin
- Impaired utilization of stored iron à due to ↑ levels of TNF-α and IL-6
• Clinical features à symptoms/signs of anemia + that of the underlying disease
• Initial lab results àlow Hb and/or Hct, low or normal MCV, ↓ reticulocyte count,
normal RDW
• Blood smear àhypochromic, microcytic or normochromic, normocytic RBCs
• Best next step à perform iron studies: - ↓ serum iron
- ↓ TIBC
- Normal transferring saturation
- Normal or ↑ serum ferritin
• Bone marrow biopsy + Prussian blue stain à ↑ stainable iron
• Management àtreatment/correction of any underlying abnormality ± large doses of
exogenous erythropoietin ± iron replacement
3
Sideroblastic Anemia
• A group of disorders of heme (protoporphyrin) synthetic pathway characterized by iron
accumulation in the perinuclear mitochondria of nucleated RBCs à “ringed”
sideroblasts
• May be hereditary (e.g. X-linked; defective δ-aminolevulinic acid (ALA) synthase) or
acquired (e.g. alcohol, isoniazid, lead poisoning, myelodysplastic syndrome)
• Sideroblastic anemia associated with myelodysplasia may progress to acute
myelogenous leukemia (AML)
• Clinical features of lead poisoning à abdominal colicky pain, peripheral neuropathy
(e.g. wrist drop, foot drop), encephalopathy, gingival lead lines, developmental delay +
symptoms/signs of anemia
• Initial lab results àlow Hb and/or Hct, low MCV, ↓ reticulocyte count
• Blood smear àdimorphic (both normocytic and microcytic) population of RBCs ±
basophilic stippling (with lead poisoning)
• Best next step à perform iron studies: - ↑ serum iron
- ↑ serum ferritin
- Normal TIBC
- ↑ transferrin saturation
• Most accurate diagnostic test (required for diagnosis) à bone marrow biopsy +
Prussian blue stain showing ↑ iron stores and ringed sideroblasts
• Management àremoval of any underlying drug/toxin + trial of vitamin B6/pyridoxine
(successful in some forms of hereditary sideroblastic anemia) ± lead chelation (e.g.
EDTA, dimercaprol)
• Packed RBC transfusion, as indicated