What is the significance of burr cells (echinocytes) in a patient's blood smear, particularly in those with a history of renal disease or liver disease?

Burr Cells (Echinocytes): Clinical Significance

Burr cells (echinocytes) are spiculated red blood cells that indicate underlying metabolic or structural abnormalities, most commonly associated with liver disease, renal disease, pyruvate kinase deficiency, and severe burns, and their presence should prompt immediate investigation of these conditions.

Morphologic Characteristics

• Burr cells appear as flat erythrocytes with short, evenly distributed spicules projecting from the cell surface, creating a characteristic "burr" or "sea urchin" appearance 1
• These cells are best visualized in wet film preparations rather than dried, stained smears, where they may be missed 1
• Echinocytes are poorly deformable and impart high viscosity to blood, potentially hindering microvascular perfusion 2

Primary Clinical Associations

Liver Disease

• In patients with liver disease, burr cells develop within seconds when normal red blood cells are exposed to abnormal high-density lipoproteins (HDL) from jaundiced patients 1
• The echinocytosis occurs through receptor-mediated binding of abnormal HDL to approximately 5,000 sites per erythrocyte, without changes in membrane cholesterol content 1
• A variable proportion (3-30%) of echinocytes is observed in pyruvate kinase deficiency, particularly after splenectomy 3
• Chronic alcoholic liver disease can cause severe hemolytic anemia characterized by circulating burr cells, with alterations in phosphatidylserine and phosphatidylinositol concentrations in the red cell membrane 4
• The degree of echinocytosis correlates with decreased plasma alpha-lipoprotein, cholesterol, and phospholipid levels in liver disease 1, 5

Renal Disease

• Burr cells appear in acute tubular necrosis (ATN) following ischemic injury, with peak circulating echinocytes occurring 1 hour after renal artery occlusion 2
• The number of circulating echinocytes shows an excellent negative correlation with creatinine clearance (r = -0.999) in ischemic ATN 2
• Echinocytes contribute to peritubular capillary congestion and deteriorating renal function by increasing resistance to capillary blood flow 2
• Many systemic conditions affect both liver and kidneys simultaneously, making burr cells a potential marker of combined organ dysfunction 6

Other Conditions

• Severe burns (>35% body surface area) cause concomitant development of echinocytes and decreased plasma lipoprotein levels 5
• Echinocyte development in burn patients presages a poor prognosis, similar to acanthocytosis in cirrhosis 5
• Pyruvate kinase deficiency shows unremarkable red cell morphology generally, but 3-30% echinocytes may appear, especially post-splenectomy 3

Diagnostic Workup Algorithm

Initial Assessment

• Order complete blood count with reticulocyte count, lactate dehydrogenase (LDH), haptoglobin, and unconjugated bilirubin to assess for hemolysis 7, 8
• Request peripheral blood smear examination using wet film preparation for optimal echinocyte visualization 1
• Obtain comprehensive metabolic panel including liver function tests (AST, ALT, alkaline phosphatase, total and direct bilirubin) and renal function tests (creatinine, BUN) 7

Liver Disease Evaluation

• Measure serum cholesterol, HDL-cholesterol, and apolipoproteins (Apo-AI and Apo-B) if liver disease is suspected 4
• Check coagulation studies (PT, PTT, fibrinogen) to assess synthetic liver function 7
• Consider iron studies (ferritin, transferrin saturation) as iron overload can occur in chronic liver disease 4

Renal Disease Evaluation

• Obtain urinalysis for hematuria and proteinuria 8
• If glomerular disease suspected, check for dysmorphic red blood cells (>80% indicates glomerular bleeding) 3
• Consider complement levels (C3, C4, CH50) if complement-mediated disease is suspected 8

Hemolytic Anemia Workup

• Perform direct antiglobulin test (DAT) to exclude immune-mediated hemolysis 8
• If microangiopathic hemolytic anemia suspected (presence of schistocytes), order ADAMTS13 activity level urgently 8
• Check for schistocytes on peripheral smear, as their presence alongside burr cells suggests thrombotic microangiopathy 7, 8

Clinical Implications and Management

Prognostic Significance

• The presence of burr cells in severely burned patients or advanced liver disease indicates poor prognosis 5
• In ischemic ATN, the magnitude of echinocyte response correlates directly with severity of renal dysfunction 2

Reversibility

• Echinocytes generated in vitro rapidly revert to normal shape when incubated with normal HDL 1
• In alcoholic liver disease, hematological parameters may normalize months after alcohol cessation, though burr cells can persist with shortened erythrocyte lifespan 4
• Treatment with adenosine-inosine or fresh plasma from healthy individuals can reverse echinocyte formation in vitro 2

Critical Pitfalls to Avoid

• Do not rely solely on dried, stained smears as echinocytes are frequently missed; request wet film examination when burr cells are suspected 1
• Do not assume burr cells indicate only one condition—they can occur in liver disease, renal disease, burns, and hemolytic disorders simultaneously 1, 4, 5, 2
• Do not overlook the possibility of pyruvate kinase deficiency in patients with chronic hemolysis and echinocytes, especially if post-splenectomy 3
• Do not dismiss the finding as artifact—true echinocytes indicate significant underlying pathology requiring investigation 1