What are the common causes of echinocytes (burr cells) and how should they be evaluated and managed?

Echinocytes (Burr Cells): Causes, Evaluation, and Management

Common Causes

Echinocytes are most commonly caused by liver disease (particularly alcoholic cirrhosis), renal failure, pyruvate kinase deficiency (especially post-splenectomy), and artifact from blood storage or preparation. 1, 2, 3

Pathologic Causes

• Liver disease: Abnormal high-density lipoproteins (HDL) in jaundiced patients bind to approximately 5,000 erythrocyte surface receptors, causing rapid shape transformation within seconds without altering membrane cholesterol content 2
• Alcoholic liver disease with hemochromatosis: Causes severe hemolytic anemia with echinocytosis through alterations in phosphatidylserine and phosphatidylinositol concentrations in the red cell membrane, even when cholesterol:phospholipid ratios remain normal 3
• Pyruvate kinase deficiency: 3-30% of red cells may be echinocytes, with marked increase after splenectomy 1
• Uremia/renal failure: Common association with echinocyte formation 4

Critical Diagnostic Pitfall

• Echinocytes are frequently found in wet film preparations but rarely detected in dried, stained smears 2, 4
• Always examine EDTA blood in a counting chamber under phase contrast microscopy or use scanning electron microscopy for confirmation, as routine blood smears dramatically underestimate echinocyte prevalence 5, 4

Evaluation Approach

Initial Laboratory Assessment

• Hemolysis markers: Elevated LDH, reduced haptoglobin, elevated unconjugated bilirubin (typically <5 mg/dL), increased reticulocyte count 1
• Liver function tests: AST, ALT, bilirubin, albumin, PT/INR to assess for hepatic dysfunction 2, 3
• Renal function: BUN, creatinine to evaluate for uremia 4
• Iron studies: Serum ferritin and transferrin saturation may be disproportionately elevated in pyruvate kinase deficiency even without transfusion history 1
• Lipid panel: Assess for decreased HDL-cholesterol and apolipoprotein abnormalities in liver disease 3, 5

Specialized Testing When Hemolysis is Present

• Pyruvate kinase enzyme activity: Indicated when immune-mediated hemolysis, membrane defects, unstable hemoglobins, and paroxysmal nocturnal hemoglobinuria have been excluded 1
• PKLR gene mutation analysis: Definitive diagnosis of pyruvate kinase deficiency requires demonstration of decreased enzyme activity and/or identification of causative mutations 1
• Exclude other causes: Direct antiglobulin test (negative in pyruvate kinase deficiency), osmotic fragility (not informative in pyruvate kinase deficiency), hemoglobin electrophoresis 1

Imaging Studies

• Bone scan or PET-CT: Not relevant for echinocyte evaluation itself, but if pyruvate kinase deficiency is suspected, look for symmetric diaphyseal/metaphyseal osteosclerosis (though this is not a feature of pyruvate kinase deficiency) 1

Management Strategy

Address Underlying Cause

• Liver disease: Cessation of alcohol intake is paramount; hematological parameters may normalize within 4 months, though echinocytes and shortened erythrocyte lifespan can persist for at least one year 3
• Hemochromatosis: Therapeutic phlebotomy or chelation therapy when identified as contributing factor 3
• Pyruvate kinase deficiency:
  • Transfusion support for severe anemia 1
  • Splenectomy consideration in selected cases, though this increases echinocyte percentage and carries thrombotic risk 1
  • Monitor for iron overload even in non-transfused patients 1
  • Prophylactic cholecystectomy consideration given high gallstone risk 1

Hemolytic Crisis Management

• Transfusion of packed red cells may be ineffective in acute alcoholic liver disease with echinocytosis, as transfused cells rapidly acquire the abnormality from circulating abnormal HDL 3
• Address precipitating factors: parvovirus B19 infection (aplastic crisis), biliary obstruction, infection 1

Monitoring

• Serial complete blood counts with reticulocyte count 1
• Bilirubin and LDH to assess ongoing hemolysis 1
• Ferritin monitoring in pyruvate kinase deficiency regardless of transfusion status 1

Key Clinical Pearls

• Echinocytes in neonates are more frequent than in adults and may not indicate pathology 4
• The normal discocyte shape represents optimal rheology; echinocytic transformation increases blood viscosity at all shear rates and can impair flow in larger vessels 6
• No echinocytogenic factor may be demonstrable in fresh plasma despite in vivo echinocytosis 4
• When echinocytosis occurs with hemolytic anemia in liver disease, consider coexistent hemochromatosis as the primary erythrocyte abnormality, with alcohol causing acute decompensation 3