Characteristics of Common Anemias

Etiology or Type	Morphologic Changes	Special Features
Blood loss, acute	Normochromic-normocytic, with polychromatophilia	If severe, possible nucleated RBCs and left shift of the WBCs Leukocytosis Thrombocytosis
Blood loss, chronic	Same as iron deficiency	Same as iron deficiency
Folate deficiency	Same as vitamin B12 deficiency	Serum folate < 5 ng/mL (< 11 nmol/L) RBC folate < 225 ng/mL RBCs (< 510 nmol/L) Nutritional deficiency and malabsorption (in sprue, pregnancy, infancy, or alcohol use disorder)
Hereditary spherocytosis	Spheroidal microcytes Normoblastic erythroid hyperplasia Reticulocytosis	Increased MCHC Increased RBC osmotic fragility Shortened survival of labeled RBCs
Warm antibody hemolytic anemia	Spheroidal microcytes Normoblastic erythroid hyperplasia Reticulocytosis	Increased MCHC Increased RBC osmotic fragility Shortened survival of labeled RBCs Positive direct antiglobulin test
Hemolysis	Normochromic-normocytic Reticulocytosis Marrow erythroid hyperplasia	Increased serum indirect bilirubin and LDH, low haptoglobin Increased stool and urine urobilinogen Hemoglobinuria in intravascular hemolysis Hemosiderinuria
Infection, cancer, chronic inflammation, or renal disease	Normochromic-normocytic early, then microcytic Normoblastic marrow Normal or increased iron stores	Decreased serum iron Decreased total iron-binding capacity Elevated serum ferritin Normal or increased marrow iron content
Iron deficiency	Microcytic, with anisocytosis and poikilocytosis Reticulocytopenia Hyperplastic marrow, with delayed hemoglobination	Possible achlorhydria, smooth tongue, angular cheilosis, and spoon nails Absent stainable marrow iron Low serum iron Increased total iron-binding capacity Low serum ferritin
Marrow failure	Normochromic-normocytic (may be macrocytic) Reticulocytopenia Failed marrow aspiration (often) or evident hypoplasia of erythroid series or of all elements	Idiopathic (>50%), hereditary, or secondary to exposure to toxic drugs or chemicals (eg, chloramphenicol, quinacrine, hydantoins, insecticides) or parvovirus B19
Marrow replacement (myelophthisis)	Anisocytosis and poikilocytosis (eg, teardrop cells) Nucleated RBCs Early granulocyte precursors Marrow aspiration possibly failing or showing leukemia, myeloma, myelofibrosis, or metastatic cells	Marrow infiltration with infectious granulomas, tumors, fibrosis, or lipid histiocytosis Possible hepatomegaly and splenomegaly Possible bone changes (osteosclerosis)
Cold agglutinin disease	Macrocytosis Red cell agglutination Reticulocytosis	Follows exposure to cold Results from a cold agglutinin or hemolysin test Sometimes postinfectious (paroxysmal cold hemoglobinuria)
Paroxysmal nocturnal hemoglobinuria	Leukopenia Thrombocytopenia Reticulocytosis	Hemoglobinuria, sometimes with frankly dark morning urine Hemosiderinuria Thrombosis Smooth muscle dystonia causing abdominal pain, esophageal spasm, erectile dysfunction Variable degree of bone marrow failure (cytopenias)
Sickle cell disease	Anisocytosis and poikilocytosis Some sickle cells in peripheral smear Sickling of all RBCs in preparation with hypoxia or hyperosmolar exposure Reticulocytosis	Most common in people of African ancestry in the United States Urinary hyposthenuria Hb S detected during electrophoresis Bone changes on x-ray Stroke and other thrombotic events Possibly painful vaso-occlusive crises and leg ulcers, stroke
Sideroblastic anemia	Usually hypochromic but dimorphic with normocytes and macrocytes Hyperplastic marrow, with delayed hemoglobination Ringed sideroblasts	Inborn or acquired metabolic defect (eg, due to substances such as alcohol, isoniazid) Usually stainable marrow iron (plentiful), but can be reduced Some congenital forms respond to vitamin B6 administration Can be part of a myelodysplastic syndrome
Thalassemia	Microcytic Target cells Basophilic stippling Anisocytosis and poikilocytosis in homozygotes Nucleated RBCs in homozygotes Reticulocytosis	Elevated Hb A2 and Hb F (in beta-thalassemia) Mediterranean ancestry (common) In homozygotes, anemia from infancy Splenomegaly Bone changes on radiographs
Vitamin B12 deficiency	Oval macrocytes Anisocytosis Reticulocytopenia Hypersegmented WBCs Megaloblastic marrow	Serum B12 < 200 pg/mL (< 145 pmol/L) Elevated methylmalonic acid and homocysteine Increased LDH Antibodies to intrinsic factor in serum (pernicious anemia) Frequently, GI and CNS symptoms
CNS = central nervous system; GI = gastrointestinal; Hb = hemoglobin; LDH = lactic dehydrogenase; MCHC = mean corpuscular hemoglobin concentration; RBC = red blood cell; WBC = white blood cell.

Etiology or Type

Morphologic Changes

Special Features

Blood loss, acute

Normochromic-normocytic, with polychromatophilia

If severe, possible nucleated RBCs and left shift of the WBCs

Leukocytosis

Thrombocytosis

Blood loss, chronic

Same as iron deficiency

Folate deficiency

Same as vitamin B12 deficiency

Serum folate < 5 ng/mL (< 11 nmol/L)

RBC folate < 225 ng/mL RBCs (< 510 nmol/L)

Nutritional deficiency and malabsorption (in sprue, pregnancy, infancy, or alcohol use disorder)

Hereditary spherocytosis

Spheroidal microcytes

Normoblastic erythroid hyperplasia

Reticulocytosis

Increased MCHC

Increased RBC osmotic fragility

Shortened survival of labeled RBCs

Warm antibody hemolytic anemia

Spheroidal microcytes

Normoblastic erythroid hyperplasia

Reticulocytosis

Increased MCHC

Increased RBC osmotic fragility

Shortened survival of labeled RBCs

Positive direct antiglobulin test

Hemolysis

Normochromic-normocytic

Reticulocytosis

Marrow erythroid hyperplasia

Increased serum indirect bilirubin and LDH, low haptoglobin

Increased stool and urine urobilinogen

Hemoglobinuria in intravascular hemolysis

Hemosiderinuria

Infection, cancer, chronic inflammation, or renal disease

Normochromic-normocytic early, then microcytic

Normoblastic marrow

Normal or increased iron stores

Decreased serum iron

Decreased total iron-binding capacity

Elevated serum ferritin

Normal or increased marrow iron content

Iron deficiency

Microcytic, with anisocytosis and poikilocytosis

Reticulocytopenia

Hyperplastic marrow, with delayed hemoglobination

Possible achlorhydria, smooth tongue, angular cheilosis, and spoon nails

Absent stainable marrow iron

Low serum iron

Increased total iron-binding capacity

Low serum ferritin

Marrow failure

Normochromic-normocytic (may be macrocytic)

Reticulocytopenia

Failed marrow aspiration (often) or evident hypoplasia of erythroid series or of all elements

Idiopathic (>50%), hereditary, or secondary to exposure to toxic drugs or chemicals (eg, chloramphenicol, quinacrine, hydantoins, insecticides) or parvovirus B19

Marrow replacement (myelophthisis)

Anisocytosis and poikilocytosis (eg, teardrop cells)

Nucleated RBCs

Early granulocyte precursors

Marrow aspiration possibly failing or showing leukemia, myeloma, myelofibrosis, or metastatic cells

Marrow infiltration with infectious granulomas, tumors, fibrosis, or lipid histiocytosis

Possible hepatomegaly and splenomegaly

Possible bone changes (osteosclerosis)

Cold agglutinin disease

Macrocytosis

Red cell agglutination

Reticulocytosis

Follows exposure to cold

Results from a cold agglutinin or hemolysin test

Sometimes postinfectious (paroxysmal cold hemoglobinuria)

Paroxysmal nocturnal hemoglobinuria

Leukopenia

Thrombocytopenia

Reticulocytosis

Hemoglobinuria, sometimes with frankly dark morning urine

Hemosiderinuria

Thrombosis

Smooth muscle dystonia causing abdominal pain, esophageal spasm, erectile dysfunction

Variable degree of bone marrow failure (cytopenias)

Sickle cell disease

Anisocytosis and poikilocytosis

Some sickle cells in peripheral smear

Sickling of all RBCs in preparation with hypoxia or hyperosmolar exposure

Reticulocytosis

Most common in people of African ancestry in the United States

Urinary hyposthenuria

Hb S detected during electrophoresis

Bone changes on x-ray

Stroke and other thrombotic events

Possibly painful vaso-occlusive crises and leg ulcers, stroke

Sideroblastic anemia

Usually hypochromic but dimorphic with normocytes and macrocytes

Hyperplastic marrow, with delayed hemoglobination

Ringed sideroblasts

Inborn or acquired metabolic defect (eg, due to substances such as alcohol, isoniazid)

Usually stainable marrow iron (plentiful), but can be reduced

Some congenital forms respond to vitamin B6 administration

Can be part of a myelodysplastic syndrome

Thalassemia

Microcytic

Target cells

Basophilic stippling

Anisocytosis and poikilocytosis in homozygotes

Nucleated RBCs in homozygotes

Reticulocytosis

Elevated Hb A2 and Hb F (in beta-thalassemia)

Mediterranean ancestry (common)

In homozygotes, anemia from infancy

Splenomegaly

Bone changes on radiographs

Vitamin B12 deficiency

Oval macrocytes

Anisocytosis

Reticulocytopenia

Hypersegmented WBCs

Megaloblastic marrow

Serum B12 < 200 pg/mL (< 145 pmol/L)

Elevated methylmalonic acid and homocysteine

Increased LDH

Antibodies to intrinsic factor in serum (pernicious anemia)

Frequently, GI and CNS symptoms

CNS = central nervous system; GI = gastrointestinal; Hb = hemoglobin; LDH = lactic dehydrogenase; MCHC = mean corpuscular hemoglobin concentration; RBC = red blood cell; WBC = white blood cell.

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