What is the differential diagnosis and workup for Echinocytes (Burr cells) on laboratory results?

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From the Guidelines

Burr cells on a peripheral blood smear require a comprehensive differential diagnosis and workup to identify the underlying cause, with a focus on both artifactual and pathologic causes, including uremia, liver disease, pyruvate kinase deficiency, microangiopathic hemolytic anemia, and post-splenectomy states. The primary conditions to consider include uremia, liver disease, pyruvate kinase deficiency, microangiopathic hemolytic anemia, and post-splenectomy states, as these are the most common causes of burr cells 1. Artifactual causes should also be ruled out, as improper sample handling or prolonged storage can create burr cells.

Key Considerations

  • The workup should begin with a complete blood count with differential and review of the peripheral smear to confirm the presence and quantity of burr cells.
  • Basic metabolic panel is essential to assess renal function (BUN, creatinine), as uremia is a common cause.
  • Liver function tests (ALT, AST, bilirubin, albumin) should be ordered to evaluate for hepatic disease.
  • Hemolysis markers including LDH, haptoglobin, and reticulocyte count help determine if active hemolysis is present.
  • If pyruvate kinase deficiency is suspected, specific enzyme activity testing should be performed, as the diagnosis ultimately depends upon the demonstration of decreased enzyme activity and/or the identification of causative mutations in PKLR gene 1.

Clinical History and Physical Examination

Clinical history is crucial, particularly regarding splenectomy status, medication use, and underlying conditions. The presence of burr cells reflects membrane damage to erythrocytes, often due to toxin exposure (as in uremia) or metabolic derangements affecting the lipid composition of the cell membrane. Treatment should target the underlying cause rather than the burr cells themselves, as they are a manifestation of an underlying disorder. A proposed diagnostic flowchart of hemolytic anemia can be used to guide the workup, as seen in Supporting Information Figure S4 1.

From the Research

Differential Diagnosis for Burr Cells

  • Burr cells, also known as echinocytes, are abnormal red blood cells that can be seen in various conditions, including uremia, pyruvate kinase deficiency, and liver disease 2, 3.
  • The presence of Burr cells on a laboratory test can indicate a range of underlying conditions, and a thorough workup is necessary to determine the cause.

Workup for Burr Cells

  • A complete blood count (CBC) is a crucial test in the workup for Burr cells, as it can provide information on the red blood cell count, hemoglobin, hematocrit, and red blood cell indices 2.
  • A peripheral blood film (PBF) is also an essential test, as it allows for the examination of the morphology of red blood cells and can help identify Burr cells 4.
  • Additional tests, such as renal function tests, liver function tests, and enzyme assays, may be necessary to determine the underlying cause of the Burr cells 3.

Clinical Considerations

  • The interpretation of Burr cells on a laboratory test requires consideration of the patient's clinical history and physical examination findings 4.
  • A structured approach to the workup, including the use of diagnostic algorithms, can help clinicians identify the underlying cause of the Burr cells and develop an appropriate treatment plan 3.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

The complete blood count: physiologic basis and clinical usage.

The Journal of perinatal & neonatal nursing, 1997

Research

Peripheral blood film - a review.

Annals of Ibadan postgraduate medicine, 2014

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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