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Reference Guide
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Crenated Cells
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Crenated Cells

Crenated cells are red blood cells (RBCs) with a spiky, scalloped appearance caused by water loss due to hypertonic conditions, slide preparation artifacts, or underlying medical conditions such as dehydration and uremia. 

Identifying crenation on a peripheral blood smear can provide valuable insights into fluid balance, kidney function, and metabolic status, making it an important morphological finding in clinical assessments.

What Are Crenated Cells?

Crenated cells are red blood cells (RBCs) that exhibit a scalloped or spiky appearance due to shrinkage. These morphological changes can occur for a variety of reasons, ranging from benign artifacts to underlying medical conditions that require further evaluation.

The primary causes of crenation include:

  • Hypertonic solutions: when RBCs are exposed to a hypertonic environment, water exits the cells via osmosis, leading to cell shrinkage and the characteristic spiky shape.
    • Hypertonic environments can be due to underlying medical conditions, or due to medical interventions. Hypertonic IV solutions, such as 3% saline, 5% dextrose in saline, or mannitol, are administered in clinical settings to treat conditions like severe hyponatremia, cerebral edema, or shock, and can lead to RBC crenation by drawing water out of the cells due to osmotic pressure differences.
  • Artifacts from slide preparation: improper handling or delayed blood smear preparation can create artificial crenation, which may not be clinically significant.
  • Underlying medical conditions: conditions such as dehydration, uremia, and severe electrolyte imbalances can also cause a hypertonic environment in the blood and may contribute to RBC crenation. Of these, hypernatremia (high sodium) and hyperglycemia are main causes.

It is also essential to differentiate echinocytes from acanthocytes:

  • Echinocytes (burr cells) are red blood cells with multiple small, evenly spaced projections across their surface, often resulting from artifacts or specific medical conditions such as uremia and liver disease.
  • Acanthocytes (spur cells) are red blood cells with irregular, spiked projections of varying length and distribution, associated with severe liver disease and neuroacanthocytosis syndromes.

Echinocytes have uniform, reversible projections, while acanthocytes have irregular, irreversible projections due to membrane lipids and splenic remodeling alterations. Echinocytes are often artifactual or transient, whereas acanthocytes are pathological markers of serious disease.

Who Should Be Tested for Crenated Cells?

Crenated cells are usually identified incidentally on a peripheral blood smear. However, their presence may warrant further evaluation in certain populations, including:

  • Individuals undergoing routine blood tests with unexplained abnormal findings.
  • Patients presenting with symptoms of dehydration, kidney dysfunction, or metabolic imbalances, such as excessive thirst, low urine output, or confusion.
  • Individuals with chronic conditions, including diabetes, liver disease, or uremia, who are at risk for fluid and electrolyte disturbances.
  • Patients experiencing anemia-related symptoms, such as unexplained fatigue, pallor, dizziness, or shortness of breath, where crenation may suggest underlying dehydration or metabolic shifts.

Testing Procedure

A peripheral blood smear is a diagnostic test that examines blood cell morphology under a microscope. It is performed by spreading a drop of blood thinly on a slide, staining it with Wright's stain, and analyzing cell size, shape, and structure using oil immersion microscopy.

Key Steps

Key steps generally include: 

Preparation

A well-made smear should be thin enough for individual red blood cells (RBCs) to be visible with a central pallor.

Staining

Wright's stain highlights RBCs, white blood cells (WBCs), and platelets.

Examination

  • RBCs are assessed for shape variations (e.g., spherocytes, target cells, schistocytes), size differences (anisocytosis), and color (anisochromia).
  • WBCs are evaluated for abnormalities such as toxic granulation or nuclear segmentation changes.
  • Platelets are checked for size, granularity, and clumping.

What Do High Levels of Crenated Cells Mean?

An increased presence of crenated cells may indicate:

However, there is potential for misinterpretation; distinguishing between true crenation and laboratory artifacts is essential for accurate clinical assessment.

What Do Low Levels of Crenated Cells Mean?

A low or absent presence of crenated cells is typically a normal finding in healthy individuals. However, changes in crenation levels over time may provide insights into treatment response:

  • Reduction after proper hydration suggests effective fluid resuscitation in previously dehydrated patients.
  • Correction of electrolyte imbalances (e.g., normalization of sodium levels) may restore RBC morphology.
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See References

An R, Wipf DO, Minerick AR. Spatially variant red blood cell crenation in alternating current non-uniform fields. Biomicrofluidics. 2014 Mar 5;8(2):021803. doi: 10.1063/1.4867557. PMID: 24753734; PMCID: PMC3977840.

Arumugham VB, Shahin MH. Therapeutic Uses of Diuretic Agents. [Updated 2023 May 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557838/

Langsdorf LJ, Zydney AL. Effect of uremia on the membrane transport characteristics of red blood cells. Blood. 1993 Feb 1;81(3):820-7. PMID: 8427973.

Lynch EC. Peripheral Blood Smear. In: Walker HK, Hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990. Chapter 155. Available from: https://www.ncbi.nlm.nih.gov/books/NBK263/

Maham Bakhtyar, MBBS. (2024, May 2). Spur Cell Anemia: Practice Essentials, Pathophysiology, Etiology. Medscape.com; Medscape. https://emedicine.medscape.com/article/206314-overview#showall

Maldonado KA, Mohiuddin SS. Biochemistry, Hypertonicity. [Updated 2023 Aug 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK541095/

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