Hematology
Anemia — by MCV, comprehensively
Hematology

Anemia — by MCV, comprehensively

Microcytic, normocytic, macrocytic causes — and the smear findings that nail each one.

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◆Microcytic (MCV < 80)

  • •Iron deficiency: ↓ ferritin (most specific), ↑ TIBC, ↓ transferrin saturation; pica; blood loss until proven otherwise
  • •Anemia of chronic disease: ↑ ferritin (acute-phase), ↓ TIBC, normal-low serum iron; treat underlying inflammation
  • •Thalassemia: target cells, basophilic stippling; trait → microcytic with NORMAL iron studies; α has 4 alleles, β has 2
  • •Sideroblastic anemia: ringed sideroblasts on marrow; causes: lead, alcohol, isoniazid (give B6), copper deficiency, MDS
  • •Lead poisoning: basophilic stippling, microcytic anemia, abdominal pain, neuropathy; check serum lead; chelate with succimer (peds) or EDTA

◆Normocytic (MCV 80–100)

  • •Anemia of chronic kidney disease: ↓ EPO; treat with EPO replacement when Hb <10, iron stores adequate
  • •Hemolysis: ↑ LDH, ↑ indirect bili, ↓ haptoglobin, ↑ reticulocytes
  • •Hereditary spherocytosis: NORTHERN European, family history, ↑ MCHC, NEGATIVE Coombs, splenomegaly; splenectomy if severe
  • •G6PD deficiency: oxidative stress (sulfa, antimalarials, fava beans, infections) → bite cells + Heinz bodies; check level after acute episode resolves
  • •Warm AIHA: IgG, spherocytes, POSITIVE direct Coombs; SLE, CLL, drugs (methyldopa); steroids first-line
  • •Cold AIHA: IgM, Mycoplasma, EBV; cold avoidance; rituximab refractory
  • •MAHA: schistocytes; TTP/HUS/DIC/HELLP/malignant HTN/mechanical valves

◆Macrocytic (MCV > 100)

  • •B12 deficiency: ↑ MMA + ↑ homocysteine; neuro symptoms (subacute combined degeneration); pernicious anemia (autoimmune anti-IF), strict vegan, ileal disease
  • •Folate deficiency: ↑ homocysteine + NORMAL MMA; no neuro symptoms; alcoholics, methotrexate, pregnancy
  • •Non-megaloblastic: alcohol, liver disease, hypothyroidism, MDS, drugs (hydroxyurea, zidovudine)
  • •Reticulocytosis: any cause of hemolysis or recent bleeding can cause apparent macrocytosis

◆Special situations

  • •Sickle cell disease: vaso-occlusive crisis, acute chest syndrome, splenic sequestration in kids, aplastic crisis (parvovirus B19)
  • •Hydroxyurea reduces SCD crises; transfusions for severe; vaccinations critical (Pneumococcus, Hib, Meningococcus due to functional asplenia)
  • •Paroxysmal nocturnal hemoglobinuria: morning dark urine + thrombosis + pancytopenia; CD55/CD59 deficiency; eculizumab
  • •Aplastic anemia: pancytopenia + hypocellular marrow + NO hepatosplenomegaly; idiopathic, drugs (chloramphenicol, sulfa), viruses; stem cell transplant
  • •Pure red cell aplasia: only RBC line affected; parvovirus B19 (esp in immunocompromised) or thymoma

Smear findings ↔ diagnosis

Smear findingDiagnosis
Target cellsThalassemia, HbC, liver disease, asplenia
SchistocytesMAHA (TTP/HUS/DIC/HELLP)
SpherocytesHereditary spherocytosis, warm AIHA
Bite cells / Heinz bodiesG6PD deficiency
Basophilic stipplingLead poisoning, thalassemia
Howell-Jolly bodiesAsplenia (functional or surgical)
Ringed sideroblastsSideroblastic anemia, MDS
Tear drop cellsMyelofibrosis
Hypersegmented neutrophilsB12 / folate deficiency
Auer rodsAML (APL has the most)

High-yield pearls

  • ◆B12 deficiency: ↑ MMA AND ↑ homocysteine; folate deficiency only ↑ homocysteine (MMA normal)
  • ◆↑ ferritin + ↓ TIBC in chronic inflammation = anemia of chronic disease (not iron deficiency)
  • ◆Microcytic anemia + NORMAL iron studies + ↑ HbA2 = β-thalassemia trait — DO NOT give iron
  • ◆Negative Coombs + spherocytes + family history = hereditary spherocytosis (not warm AIHA)
  • ◆Mechanical valve + chronic anemia + schistocytes = valve hemolysis → echo to assess paravalvular leak
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