What the CBC Measures
- Red cell line: RBC count, hemoglobin, hematocrit, MCV, MCH, MCHC, and RDW
- White cell line: total WBC count plus the differential (neutrophils, lymphocytes, monocytes, eosinophils, basophils)
- Platelets: platelet count, and sometimes mean platelet volume (MPV)
Symptoms and Signs of Anemia
General symptoms — fatigue, dyspnea on exertion, pallor, tachycardia, lightheadedness — scale with how severe and how fast the anemia developed; a slow drop is often tolerated far better than a rapid one. Some signs point to a specific cause: koilonychia (spoon nails) and pica in iron deficiency, jaundice and dark urine in hemolysis, and glossitis with peripheral neuropathy in B12 deficiency.
Approaching Anemia by MCV
| Category | MCV | Common causes |
|---|---|---|
| Microcytic | <80 fL | Iron deficiency, thalassemia, anemia of chronic disease, sideroblastic anemia |
| Normocytic | 80-100 fL | Acute blood loss, anemia of chronic disease, hemolysis, renal disease, marrow failure |
| Macrocytic | >100 fL | B12/folate deficiency, hypothyroidism, liver disease, alcohol, myelodysplasia, reticulocytosis |
Microcytic Anemia (MCV <80 fL)
Iron deficiency anemia is the most common cause worldwide. It develops in stages — depleted iron stores (low ferritin) precede a fall in MCV, so early iron deficiency can still have a normal MCV. Causes include chronic blood loss (GI, menstrual), malabsorption (celiac disease, post-gastrectomy), and increased demand (pregnancy, growth). RDW is typically elevated, since new larger cells mix with older microcytic ones as the deficiency develops.
Thalassemia trait produces uniformly small cells from birth, so RDW is typically normal, and the RBC count is often normal-to-high (the marrow compensates with more, smaller cells) rather than low. The Mentzer Index (MCV ÷ RBC count) is a quick screen to tell the two apart before confirmatory testing (iron studies vs. hemoglobin electrophoresis).
Anemia of chronic disease is usually normocytic but can be mildly microcytic; it reflects inflammation-driven iron sequestration (via hepcidin) rather than true iron deficiency — ferritin is normal or high, unlike in true iron deficiency.
Sideroblastic anemia results from defective heme synthesis despite adequate iron; causes include lead poisoning, certain drugs (isoniazid, linezolid), alcohol use, and rare congenital forms.
Normocytic Anemia (MCV 80-100 fL)
Acute blood loss is initially normocytic — the MCV doesn't change until new, different-sized cells are produced in response.
Hemolytic anemia involves premature red cell destruction, either intravascular (within vessels, e.g. mechanical heart valves, TTP/HUS, severe DIC) or extravascular (in the spleen/liver, e.g. autoimmune hemolytic anemia, hereditary spherocytosis, G6PD deficiency, sickle cell disease). Hemolysis labs: elevated reticulocyte count (marrow responding appropriately), elevated LDH, low haptoglobin, elevated indirect bilirubin. Peripheral smear clues include schistocytes (mechanical/microangiopathic hemolysis), spherocytes (hereditary spherocytosis or autoimmune hemolysis), and sickle cells.
Anemia of renal disease results from reduced erythropoietin production as kidney function declines — see the CKD-EPI calculator for staging.
Bone marrow failure (aplastic anemia, marrow infiltration by malignancy) typically presents with normocytic anemia alongside low white cells and platelets (pancytopenia), with a low reticulocyte count reflecting marrow underproduction.
Macrocytic Anemia (MCV >100 fL)
Macrocytic anemia splits into megaloblastic and non-megaloblastic causes.
Megaloblastic (B12 or folate deficiency): impaired DNA synthesis produces large, immature red cells. B12 deficiency causes include pernicious anemia (autoimmune loss of intrinsic factor), malabsorption (post-gastrectomy, ileal disease), strict vegan diets, and metformin use. Folate deficiency causes include poor dietary intake, alcoholism, increased demand (pregnancy, hemolysis), and certain drugs (methotrexate, some anticonvulsants). A hallmark smear finding is hypersegmented neutrophils. B12 deficiency specifically can also cause neurological symptoms (peripheral neuropathy, ataxia, cognitive changes) independent of anemia severity — and these can occur even before anemia is apparent.
Non-megaloblastic causes include liver disease, hypothyroidism, chronic alcohol use (a direct marrow toxic effect, separate from any folate deficiency), myelodysplastic syndrome, and certain medications (e.g. hydroxyurea). A high reticulocyte count itself can also mildly elevate the MCV, since reticulocytes are larger than mature red cells.
A Simple Anemia Workup
- Confirm anemia (hemoglobin below the reference range for age and sex)
- Check MCV to categorize as microcytic, normocytic, or macrocytic
- Check the reticulocyte count — low suggests underproduction (marrow failure, nutritional deficiency); high suggests increased turnover (hemolysis, bleeding) or an appropriate marrow response
- Order targeted tests based on the category and reticulocyte response: iron studies, B12/folate, hemolysis labs (LDH, haptoglobin, bilirubin), or a peripheral smear
White Cell Differential
- Neutrophilia: bacterial infection, stress response, steroid use, tissue necrosis
- Neutropenia: viral infection, marrow suppression (chemotherapy, certain drugs), severe sepsis (consumption)
- Lymphocytosis: viral infection, chronic lymphocytic leukemia
- Eosinophilia: allergy/atopy, parasitic infection, drug reactions
Platelets
- Thrombocytopenia: decreased production (marrow failure, B12 deficiency), increased destruction (ITP, DIC, hypersplenism), or dilutional (massive transfusion)
- Thrombocytosis: reactive (infection, inflammation, iron deficiency, post-splenectomy) versus primary (essential thrombocythemia)