What is the meaning of crenated Red Blood Cells (RBCs)?

Crenated Red Blood Cells (Echinocytes): Definition and Clinical Significance

Crenated RBCs, also called echinocytes or burr cells, are red blood cells with multiple small, evenly-spaced spiny projections on their surface, representing a morphological abnormality that indicates membrane alterations from metabolic disturbances, storage lesions, or artifact.

Morphological Characteristics

Crenated RBCs display distinctive features that distinguish them from normal biconcave discocytes:

• Multiple uniform spicules project from the cell surface in a regular, evenly-distributed pattern 1
• Progressive transformation occurs through echinocyte stages (Type I through Type III), with Type II-III showing 80-100% crenation in severe cases 2
• Sphero-echinocytic forms may develop, representing advanced membrane damage with both crenation and sphering 1

Pathophysiological Mechanisms

Membrane Alterations

• Phospholipid asymmetry develops from oxidative stress damaging RBC membranes, triggering eryptosis (programmed RBC death) 3
• Calcium dysregulation and increased ceramide levels alter membrane structure, particularly in uremic conditions 3
• Surface-to-volume ratio changes decrease RBC deformability, a critical factor for microcirculatory flow 4

Metabolic Disturbances

• Uremic toxins in chronic kidney disease directly stimulate eryptosis, raising cytosolic calcium and enhancing ceramide formation 3
• Hyperbilirubinemia from hepatic failure triggers eryptosis through direct effects of bile acids and bilirubin on RBC membranes 3
• Oxidative stress causes lipid peroxidation in conditions including hypertension and neurological disorders 3

Clinical Causes

Renal Disease

• Chronic kidney disease and end-stage renal disease are primary causes, with parathyroid hormone levels correlating with eryptosis severity 3
• Uremia produces the classic "burr cell" appearance on peripheral smear 3

Hepatic Disease

• Hepatic failure increases eryptotic erythrocyte percentage through hyperbilirubinemia 3
• Bile acid accumulation has direct membrane-damaging effects 3

Microangiopathic Conditions

• Hemolytic uremic syndrome produces burr cells as diagnostic indicators of microangiopathic hemolytic anemia 3
• Low flow states and shock cause in vivo crenation visible in microcirculation, with nearly all RBCs becoming crenated spheres during refractory shock 4

Storage Lesion

• Blood preservation with acid citrate dextrose produces 80-100% crenated cells by 17-21 days of storage 2
• Reduced deformability from storage accelerates splenic clearance, with altered RBCs selectively removed within 24 hours post-transfusion 5
• Internal hemoglobin crystallization may occur in stored blood, appearing anisotropic under polarized light microscopy 2

Artifact vs. Pathology

Temperature-Dependent Changes

• Glass effect causes artifactual crenation between flat surfaces (e.g., hemacytometer) at 32-36°C, with sphero-echinocytic state at 34°C 1
• Surface interactions with various materials (glass, polymers, mica) induce crenation when RBC distance is 0.1 mm 1

Preventable Artifacts

• Albumin presence stabilizes discocyte morphology and prevents artifactual crenation 1
• Hematocrit concentration inversely correlates with crenation degree—higher concentrations decrease artifactual changes 1
• EDTA and potassium chloride media promote crenation in washed samples 1

Clinical Implications

Diagnostic Workup

• Investigate renal function with BUN, creatinine, and urinalysis when burr cells are identified 3
• Assess hepatic function with liver enzymes, bilirubin, and coagulation studies 3
• Evaluate for microangiopathic hemolytic anemia with LDH, haptoglobin, and peripheral smear review 3

Functional Consequences

• Decreased filterability correlates with increased proportion of crenated cells, with >50% increase in critically ill patients (P < 0.001) 2
• Impaired deformability causes splenic retention and accelerated clearance from circulation 5
• Increased blood viscosity from altered internal RBC viscosity contributes to microcirculatory dysfunction in shock 2, 4

Therapeutic Considerations

• Optimize dialysis in uremic patients to reduce toxin-mediated eryptosis 3
• Address oxidative stress through treatment of underlying conditions to reduce burr cell formation 3
• Avoid transfusion of aged blood when possible, as storage-induced crenation reduces post-transfusion RBC survival 5

Common Pitfalls

• Mistaking artifact for pathology: Always correlate with clinical context, as the "glass effect" produces reversible crenation unrelated to disease 1
• Overlooking renal/hepatic causes: Burr cells should prompt immediate investigation of kidney and liver function 3
• Ignoring transfusion implications: Stored blood with extensive crenation has markedly reduced post-transfusion viability and increased viscosity 2, 5