What is anisopoikilocytosis with pencil-shaped cells?

Anisopoikilocytosis with Pencil-Shaped Cells

Anisopoikilocytosis with pencil-shaped cells is a characteristic morphologic finding most strongly associated with iron deficiency anemia, representing variation in red blood cell size (anisocytosis) and shape (poikilocytosis) with elongated, pencil-like erythrocytes that serve as a key diagnostic clue for this condition.

Definition and Morphologic Features

Anisopoikilocytosis describes the presence of red blood cells that vary in both:

• Size (anisocytosis): Red cells of different dimensions appearing on peripheral blood smear 1
• Shape (poikilocytosis): Red cells with abnormal morphology, including the characteristic pencil-shaped cells (also called elliptocytes or cigar cells) 1

Pencil cells are elongated erythrocytes with a thin, cigar-like or pencil-like appearance that result from membrane abnormalities and hemoglobin deficiency 2.

Primary Clinical Significance: Iron Deficiency Anemia

The combination of anisopoikilocytosis with pencil cells most strongly indicates iron deficiency anemia (IDA). 2

Supporting Evidence

• Pencil cells were observed in 78% of iron deficiency anemia cases compared to only 37% in beta-thalassemia minor and 13% in anemia of chronic disease 2
• Pencil cells averaged 0.78 per 1,000 RBCs in IDA versus 0.21 in beta-thalassemia and 0.075 in anemia of chronic disease, demonstrating significantly higher frequency in iron deficiency 2
• Prekeratocytes (a related poikilocyte) also appear more commonly and numerously in IDA than other microcytic anemias 2

Differential Diagnosis

While pencil cells strongly suggest iron deficiency, anisopoikilocytosis can appear in several other conditions:

Myelodysplastic Syndromes (MDS)

• Anisocytosis and poikilocytosis are recognized dysplastic features in the erythroid lineage on peripheral blood examination 1
• MDS typically presents with macrocytic anemia rather than the microcytic pattern of iron deficiency 1
• Additional dysplastic features help distinguish MDS: basophilic stippling, binuclearity, internuclear bridging, and megaloblastoid changes in bone marrow 1

Hemolytic Anemias

• Anisopoikilocytosis with tear-drop forms and polychromasia can indicate hemolysis 3
• Hereditary membrane disorders (hereditary pyropoikilocytosis, hereditary elliptocytosis) show marked anisopoikilocytosis with elliptocytes and RBC fragments 4
• Hemolysis is confirmed by low haptoglobin, elevated LDH, elevated unconjugated bilirubin, and elevated reticulocyte count 5

Thalassemia

• Beta-thalassemia minor shows anisopoikilocytosis but with fewer pencil cells than iron deficiency 2
• Target cells are present in similar numbers in both IDA and thalassemia, making them less useful for discrimination 2
• Basophilic stippling appears in only 17% of beta-thalassemia cases 2

Other Conditions

• Congenital dyserythropoietic anemia presents with anisopoikilocytosis including tear-drop forms 3
• Hemoglobin H disease may show mild anisopoikilocytosis with hypochromia 6
• CAD deficiency manifests with anemia and anisopoikilocytosis alongside neurologic symptoms 7

Diagnostic Approach

When encountering anisopoikilocytosis with pencil cells:

1. Obtain iron studies immediately: serum ferritin, transferrin saturation, and serum iron to confirm or exclude iron deficiency 1

2. Check complete blood count with indices:

   • Iron deficiency typically shows microcytic (low MCV), hypochromic anemia 2
   • MDS more commonly presents with macrocytic anemia 1

3. Assess reticulocyte count:

   • Low reticulocytes suggest inadequate bone marrow response (iron deficiency, MDS) 5
   • Elevated reticulocytes indicate hemolysis or appropriate response to blood loss 5

4. If iron deficiency is excluded, consider:

   • Hemolysis markers: haptoglobin, LDH, unconjugated bilirubin 5
   • Vitamin B12 and folate levels to exclude megaloblastic anemia 1
   • Bone marrow examination if MDS is suspected, particularly in elderly patients with unexplained cytopenias 1

Clinical Pitfalls

• Do not assume target cells distinguish thalassemia from iron deficiency—they appear in similar numbers in both conditions 2
• Basophilic stippling is not a reliable marker for thalassemia—it appears in less than 20% of cases 2
• Always confirm iron deficiency with laboratory studies rather than relying solely on morphology, as pencil cells can occasionally appear in other conditions 2
• In patients with persistent cytopenias despite iron replacement, bone marrow examination is mandatory to exclude MDS 1