What is polikilocytosis (variation in red blood cell shape)?

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What is Poikilocytosis?

Poikilocytosis refers to the presence of abnormally shaped red blood cells (RBCs) in the peripheral blood, representing a deviation from the normal biconcave disc morphology. This finding indicates underlying pathology affecting RBC production, structure, or destruction 1.

Clinical Significance

Poikilocytosis is not a diagnosis itself but rather a laboratory finding that signals various underlying conditions:

  • Iron deficiency anemia causes shape changes from normal biconcave disks to rigid microcytic microspheres, particularly when combined with polycythemia in cyanotic heart disease 2
  • Myelodysplastic syndromes (MDS) present with dysplastic erythropoiesis and various poikilocyte forms, often accompanied by other dysplastic features like pseudo-Pelger-Huët cells 3
  • Myelofibrosis and myeloproliferative disorders commonly show teardrop cells (dacrocytes), a specific type of poikilocyte 3
  • Vitamin B12 deficiency can cause marked poikilocytosis that mimics schistocytes, potentially leading to misdiagnosis as thrombotic microangiopathy 4
  • Malignancy, particularly adenocarcinoma of the gastrointestinal tract with metastatic disease, shows poikilocytosis in 12% of cases and carries poor prognosis (50% mortality within one month) 5

Diagnostic Approach

Peripheral blood smear examination is essential for identifying poikilocytosis and characterizing the specific RBC shape abnormalities present 2, 1.

Key Morphological Patterns to Identify:

  • Schistocytes (fragmented cells) suggest microangiopathic hemolytic anemia rather than marrow pathology 3
  • Teardrop cells point toward myelofibrosis or marrow infiltration 3
  • Acanthocytes and echinocytes (spiculated cells) may indicate membrane defects or metabolic abnormalities 6
  • Macrocytic poikilocytes with hypersegmented neutrophils suggest megaloblastic anemia from B12 or folate deficiency 4

Critical Laboratory Evaluation:

  • Complete blood count to assess for anemia, thrombocytopenia, and mean corpuscular volume 4, 6
  • Reticulocyte count distinguishes hemolytic processes (elevated) from production defects (low); notably, B12 deficiency shows low reticulocytes despite hemolysis 4
  • LDH and haptoglobin assess for hemolysis; LDH >2500 IU/L more commonly indicates B12 deficiency than thrombotic microangiopathy 4
  • Iron studies and B12/folate levels to identify nutritional deficiencies 2, 4

When to Pursue Bone Marrow Examination:

Bone marrow aspiration and biopsy with reticulin staining is necessary when MDS, myelofibrosis, or other marrow pathology is suspected, particularly with concurrent cytopenias, dysplastic features, or unexplained poikilocytosis 3.

  • Cytogenetic and molecular testing should accompany marrow examination, as chromosomal abnormalities occur in up to 80% of MDS patients 3
  • Flow cytometry helps distinguish clonal from reactive causes 7

Common Pitfalls to Avoid:

  • Do not confuse marked poikilocytosis from B12 deficiency with true schistocytes from thrombotic microangiopathy; check reticulocyte count (low in B12 deficiency) and B12 levels before initiating plasma exchange 4
  • Do not overlook poikilocytosis in non-anemic patients with cancer, as it carries prognostic significance independent of hemoglobin level 5
  • Ensure proper anticoagulant volume when collecting samples from polycythemic patients, as excess anticoagulant can falsely suggest coagulation abnormalities 2
  • In neonates with hemolytic anemia and poikilocytosis, consider infantile pyknocytosis, which resolves spontaneously and may respond to erythropoietin rather than requiring transfusion 8

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Teardrop Cells in Hematological Disorders

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

B12 deficiency leading to marked poikilocytosis versus true schistocytosis, a pernicious problem.

Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis, 2017

Research

Poikilocytosis in cancer patients.

California medicine, 1967

Guideline

Nucleated Red Blood Cells in Peripheral Blood: Clinical Significance and Diagnostic Approach

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

[Infantile pyknocytosis: A cause of noenatal hemolytic anemia. Is recombinant erythropoietin an alternative to transfusion?].

Archives de pediatrie : organe officiel de la Societe francaise de pediatrie, 2016

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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