Peripheral Blood Smear in Different Types of Anemia

← Back to Index(🩸 Hematology and Oncology)

Overview of Morphologic Evaluation

Blood smear examination constitutes an essential primary diagnostic step in anemia evaluation.
Classifies anemia morphologically (microcytic, normocytic, macrocytic).
Identifies specific red blood cell (RBC) shape abnormalities (poikilocytosis) and size variations (anisocytosis) guiding targeted investigations.

Findings by Anemia Etiology

Nutritional Anemias

Iron Deficiency Anemia (IDA)

RBC Morphology: Microcytic and hypochromic.
Variation: Pronounced anisocytosis and poikilocytosis.
Specific Shapes: Few ovalocytes and teardrop cells present.
Associated Findings: Thrombocytosis commonly observed.

Megaloblastic Anemia (B12/Folate Deficiency)

RBC Morphology: Macrocytic; predominantly macro-ovalocytes.
Variation: Marked anisocytosis and poikilocytosis.
Inclusions: Teardrop cells, Cabot rings, Howell-Jolly bodies, and punctate basophilia.
Associated Findings: Hypersegmented neutrophils (>5 lobes) pathognomonic. Giant metamyelocytes present.

Hemoglobinopathies & Thalassemias

Thalassemia Syndromes

Thalassemia Trait: Marked hypochromia, microcytosis, target cells, fine basophilic stippling.
Thalassemia Major: Severe hypochromia, extreme microcytosis, massive anisocytosis.
Specific Features: Fragmented RBCs, teardrop cells, numerous nucleated RBCs, polychromatophilia.

Sickle Cell Disease (HbSS)

RBC Morphology: Sickled cells (irreversibly sickled cells), target cells.
Inclusions: Howell-Jolly bodies (indicating functional hyposplenism), nucleated RBCs.
Associated Findings: Polychromasia (reflecting reticulocytosis), neutrophilia.

Hemoglobin C & E Diseases

HbC Disease: Numerous target cells, occasional spherocytes. Characteristic intracellular rhomboidal hemoglobin crystals.
HbE Disease: Microcytosis, hypochromia, prominent target cells.

Red Cell Membrane & Cytoskeleton Defects

Hereditary Spherocytosis

RBC Morphology: Spherocytes (hyperchromic, spherical, lack central pallor).
Size: Microspherocytes typical. Low-normal MCV, elevated MCHC.
Associated Findings: Polychromatophilic reticulocytes.

Hereditary Elliptocytosis & Pyropoikilocytosis

Hereditary Elliptocytosis (HE): Normochromic, normocytic elliptocytes (cigar-shaped) comprising 25-90% of cells.
Hereditary Pyropoikilocytosis (HPP): Extreme microcytosis (MCV 50-65 fL). Extraordinary variation in size/shape. Bizarre poikilocytes, RBC fragments, budding red cells, microspherocytes.

Hereditary Stomatocytosis & Acanthocytosis

Stomatocytosis: Stomatocytes exhibit linear, slit-like central pallor (bowl-shaped in 3D). Associated with macrocytosis.
Acanthocytosis: Acanthocytes (spur cells) demonstrate irregular, thorn-like spicules. Seen in abetalipoproteinemia and severe liver disease.

Erythrocyte Enzymopathies

Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency

Acute Hemolysis: "Bite cells" (degmacytes) and blister cells.
Inclusions: Heinz bodies (precipitated denatured hemoglobin) visible only with supravital stains (e.g., brilliant cresyl blue), not Wright stain.

Pyruvate Kinase (PK) Deficiency

RBC Morphology: Echinocytes (burr cells), contracted spiculated pyknocytes.
Associated Findings: Polychromatophilia and macrocytosis reflecting extreme reticulocytosis.

Microangiopathic Hemolytic Anemias (MAHA)

Etiologies: Hemolytic-Uremic Syndrome (HUS), Thrombotic Thrombocytopenic Purpura (TTP), Disseminated Intravascular Coagulation (DIC).
RBC Morphology: Schistocytes (RBC fragments), helmet cells, burr cells, triangular shapes, microspherocytes.

Summary of Specific Erythrocyte Morphologies

Morphologic Finding	Pathophysiologic Description	Key Differential Diagnoses
Target Cells	Increased surface-to-volume ratio	Thalassemia, HbC/HbE disease, Liver disease, Severe iron deficiency, Asplenia, Abetalipoproteinemia.
Spherocytes	Decreased surface-to-volume ratio, hyperdense	Hereditary spherocytosis, Autoimmune hemolytic anemia, ABO incompatibility, Burns, Hypersplenism.
Schistocytes	Helmet/triangular fragments from vascular impact	MAHA (DIC, HUS, TTP), Kasabach-Merritt syndrome, Artificial heart valves, Severe burns.
Acanthocytes	Irregular, wide-based spicules (spur cells)	Liver disease, Abetalipoproteinemia, Hypothyroidism, Post-splenectomy.
Echinocytes	Evenly distributed short spicules (burr cells)	Renal failure, PK deficiency, Liver disease, Dehydration, Artifact.
Teardrop Cells	Dacrocytes; stretched during marrow exit	Thalassemia major, Myelofibrosis, Bone marrow infiltration, Leukoerythroblastic reaction.
Elliptocytes	Oval or cigar-shaped erythrocytes	Hereditary elliptocytosis, Iron deficiency, Megaloblastic anemia, Sickle cell trait/disease.
Basophilic Stippling	Aggregated ribosomal RNA (coarse or fine)	Lead poisoning (coarse), Thalassemia (fine), Hemolytic anemias, Iron deficiency.
Howell-Jolly Bodies	Densely stained nuclear DNA remnants	Asplenia/Hyposplenia, Sickle cell disease, Megaloblastic anemia, Severe IDA.
Nucleated RBCs	Immature RBCs escaping marrow prematurely	Severe hemolysis (Thalassemia, Sickle cell), Hypoxia, Acute bleeding, Leukoerythroblastic reaction.