What causes burr cells in red blood cells?

Causes of Burr Cells (Echinocytes) in Red Blood Cells

Burr cells (echinocytes) are primarily caused by alterations in red blood cell membrane composition, most commonly due to liver disease, uremia, and metabolic disturbances that affect the phospholipid content of the cell membrane. 1, 2

Pathophysiological Mechanisms

• Liver disease, particularly alcoholic liver disease, causes burr cell formation through alterations in phosphatidylserine and phosphatidylinositol concentrations in the red cell membrane 2
• Uremic toxins in chronic kidney disease directly trigger eryptosis (programmed red cell death) with characteristic membrane changes that can manifest as burr cells 1, 3
• Oxidative stress damages red blood cell membranes, leading to phospholipid membrane asymmetry and burr cell formation 1
• Hyperbilirubinemia triggers eryptosis by enhancing calcium influx, sphingomyelinase activation, and ceramide production, which alters membrane structure 1
• Increased blood viscosity in conditions like erythrocytosis can contribute to burr cell formation through mechanical stress on red blood cells 4

Disease-Specific Associations

Liver Disease

• Alcoholic liver disease is strongly associated with burr cell formation, with alcohol directly affecting erythrocyte membrane composition 2
• Hepatic failure and hyperbilirubinemia increase the percentage of eryptotic erythrocytes, which often appear as burr cells 1
• Bile acids and bilirubin have direct eryptotic effects on red blood cells, altering their membrane structure 1
• Hemochromatosis can cause persistent burr cell formation even after cessation of alcohol intake 2

Renal Disease

• Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are associated with increased eryptosis and burr cell formation 1
• Uremic toxins including indoxyl sulfate, acrolein, and p-cresol directly stimulate eryptosis by raising cytosolic calcium concentration and enhancing ceramide levels 1
• Hemodialysis patients show higher levels of eryptosis compared to healthy individuals, with abnormal red cell morphology 1
• Parathyroid hormone (PTH) levels in CKD correlate with the degree of eryptosis and burr cell formation 1

Other Conditions

• Preeclampsia and eclampsia are associated with increased proportions of abnormal red cells including echinocytes (burr cells) 5
• Drug-induced immune hemolytic anemia can present with burr cells as part of the hemolytic process 6
• Neurological disorders like Parkinson's and Alzheimer's diseases can trigger eryptosis through altered calcium regulation and ceramide formation 1
• Oxidative stress in various conditions including hypertension can lead to lipid peroxidation in erythrocytes and burr cell formation 1

Laboratory Significance

• The presence of burr cells on peripheral blood smear is a diagnostic indicator of microangiopathic hemolytic anemia in conditions like hemolytic uremic syndrome 1
• Burr cells in the setting of anemia should prompt investigation for underlying liver disease, renal failure, or drug-induced hemolysis 2, 3, 6
• Persistent burr cells despite normalization of other hematological parameters may indicate ongoing subclinical hemolysis 2
• The proportion of burr cells correlates with disease severity in conditions like preeclampsia and eclampsia 5

Clinical Implications

• Recognition of burr cells should prompt investigation of liver and kidney function 1
• In patients with alcoholic liver disease, cessation of alcohol intake may improve hematological parameters but burr cells may persist 2
• Patients with burr cells due to uremia may require optimization of dialysis to reduce uremic toxins 1
• Addressing underlying causes of oxidative stress may help reduce burr cell formation and associated hemolysis 1