Burr Cells (Echinocytes): Evaluation and Management
What Are Burr Cells?
Burr cells (echinocytes) are red blood cells with multiple short, evenly-spaced projections across their surface, creating a spiky or "burr-like" appearance. The most critical first step when echinocytes are identified is to distinguish artifact from true pathology by examining a fresh peripheral smear, as echinocytes commonly arise from delayed specimen processing or improper storage 1.
Artifact vs. True Pathology
Do not dismiss echinocytes as artifact without confirming on a fresh specimen and correlating with the patient's clinical picture 1. Key distinguishing features include:
- True pathologic echinocytes persist on fresh smears and correlate with clinical findings 1
- Artifactual echinocytes appear predominantly in stored or improperly handled specimens 1
- Fresh wet preparations examined by phase contrast microscopy or scanning electron microscopy after glutaraldehyde fixation confirm true echinocytosis 2
Critical Differential Diagnoses
Thrombotic Microangiopathy (TMA) – Most Urgent
Thrombotic microangiopathy must be urgently excluded; it is defined by the triad of non-immune microangiopathic hemolysis, thrombocytopenia, and organ involvement (most often renal) 1, 3.
When TMA is suspected, order ADAMTS13 activity and inhibitor titer, complete blood count with platelet count, LDH, direct antiglobulin test, peripheral-smear review, serum creatinine, and urinalysis without delay 1, 3.
Do not delay plasma exchange while awaiting ADAMTS13 results if clinical suspicion for TTP is strong, as mortality increases with delayed treatment 3. Key management points:
- If ADAMTS13 activity is <10%, initiate therapeutic plasma exchange and methylprednisolone 1 g IV daily for 3 days immediately 1, 3
- For atypical HUS (ADAMTS13 >10%), initiate eculizumab therapy together with meningococcal vaccination and penicillin prophylaxis 1, 3
- Platelet transfusion is contraindicated in TTP unless there is life-threatening bleeding 1, 3
Do not overlook TMA based solely on the presence of rare schistocytes; low schistocyte counts can occur early in disease evolution 1, 3.
Pyruvate Kinase Deficiency
Echinocytes are present in 3%–30% of patients with pyruvate-kinase (PK) deficiency, especially after splenectomy, making them a characteristic morphologic clue 1.
In PK deficiency the peripheral smear typically shows anisocytosis, poikilocytosis, and variable echinocyte proportions together with laboratory evidence of chronic hemolysis (elevated reticulocyte count, LDH, indirect bilirubin; low haptoglobin) 1.
Diagnosis of PK deficiency requires demonstration of reduced PK enzyme activity and/or identification of pathogenic PKLR gene mutations 1.
Important pitfalls:
- In PK deficiency, reticulocytosis may be disproportionately low relative to the degree of hemolysis because the spleen sequesters young red cells 1
- A normal red-cell osmotic fragility test does not exclude PK deficiency 1
Liver Disease
Echinocytes occur frequently in liver disease when blood is examined in wet films, though they are rarely detected in dried, stained smears 4. The mechanism involves:
- Abnormal high-density lipoproteins (HDL) from jaundiced patients induce discocyte-echinocyte transformation within seconds at physiologic concentrations 4
- This occurs through saturable binding to approximately 5,000 sites per erythrocyte with receptor-mediated shape change 4
- Echinocytosis occurs without change in membrane cholesterol content and is reversible with normal HDL 4
Drug-Induced Echinocytosis
Drug-associated hemolytic anemia can produce echinocytes and related morphologies 5. Specific considerations:
- Salicylate induces echinocytic transformation through direct membrane effects 6
- Oxidant drug injury produces "bite cells" (a related poikilocyte) with semicircular portions removed from the cell margin 5
- Withdrawal of the offending drug(s) and treatment of underlying diseases results in improvement of hemolytic anemia and eventual disappearance of abnormal cells 5
Comprehensive Laboratory Evaluation
Initial work-up includes a complete blood count with differential, reticulocyte count, and a careful peripheral-smear review performed by an experienced pathologist 1.
Assess hemolysis with LDH, haptoglobin, indirect bilirubin, and a direct antiglobulin test 1, 3.
A comprehensive metabolic panel (creatinine, BUN, liver-function tests) should be obtained to evaluate renal and hepatic status 1.
Additional testing based on clinical context:
- If hemolysis is confirmed without an immune cause, perform PK enzyme activity testing and consider PKLR gene-mutation analysis 1
- When renal dysfunction is present, add urinalysis and complement studies (C3, C4, CH50) to evaluate for complement-mediated hemolytic-uremic syndrome 1, 3
- Physical examination for infection should specifically assess fever, tachycardia, hypotension, and identify a potential source 1
- Obtain blood cultures (and site-specific cultures when appropriate) before starting antibiotics if infection is suspected 1
Management Strategies
For Pyruvate Kinase Deficiency
Provide supportive care with folic-acid supplementation 1.
Monitor for complications such as gallstones, iron overload, and aplastic crisis secondary to parvovirus infection 1.
Consider splenectomy only after excluding thrombophilic disorders, because post-splenectomy patients have an increased risk of thromboembolic events 1.
Regularly assess iron status (serum ferritin, transferrin-saturation) even in patients who have not received transfusions 1.
For Infection-Related Cases
Start appropriate antimicrobial therapy guided by the suspected source and severity of infection 1.
For Drug-Induced Cases
Review all medications for potential triggers and discontinue if possible 3, 5. Monitor for resolution with serial peripheral smears 5.
Transfusion Guidelines (When Applicable)
Red-cell transfusion should be reserved for symptom relief or to maintain hemoglobin at 7–8 g/dL in stable patients 1, 3.