Diagnosis and Management of Increased Poikilocytosis, Anisocytosis, and Burr Cells
The presence of increased poikilocytosis, anisocytosis, and burr cells on peripheral blood smear strongly suggests a myelodysplastic syndrome (MDS) and requires bone marrow examination with cytogenetic analysis for definitive diagnosis and risk stratification. 1
Diagnostic Approach
Initial Evaluation
- Complete blood count with red cell indices
- Comprehensive peripheral blood smear examination
- Reticulocyte count
- Serum ferritin, transferrin saturation
- C-reactive protein (CRP)
- Lactate dehydrogenase (LDH)
- Haptoglobin
- Vitamin B12 and folate levels
Peripheral Blood Findings
- Anisocytosis: variation in red cell size
- Poikilocytosis: variation in red cell shape
- Burr cells (echinocytes): spiculated red cells with short, evenly spaced projections
- Additional findings to look for:
Mandatory Diagnostic Tests
Bone marrow aspirate and biopsy to evaluate:
- Cellularity
- Dysplasia in one or more hematopoietic cell lines
- Blast percentage
- Ring sideroblasts
- Fibrosis 1
Cytogenetic analysis:
- Detection of acquired clonal chromosomal abnormalities
- Standard karyotype has highest prognostic value in MDS 1
Recommended Additional Tests
- Fluorescence in situ hybridization (FISH) if standard cytogenetics fails
- Flow cytometry immunophenotyping to detect abnormalities in various cell compartments
- Molecular testing for mutations in DNMT3A, ASXL1, TET2, JAK2, and TP53 genes 1, 2
Differential Diagnosis
Myelodysplastic Syndromes (MDS)
- Primary consideration with peripheral blood showing anisocytosis, poikilocytosis, and dysplastic features
- Characterized by ineffective hematopoiesis, peripheral cytopenias, and risk of progression to acute myeloid leukemia 1
Pyruvate Kinase Deficiency
- Can present with anisocytosis and poikilocytosis
- Usually has echinocytes (3-30%), particularly after splenectomy
- Characterized by chronic hemolysis with increased reticulocyte count, LDH, and bilirubin 1
Iron Deficiency Anemia
- Can present with anisocytosis and poikilocytosis
- Typically has low serum ferritin (<30 μg/L without inflammation)
- With inflammation, ferritin up to 100 μg/L may still indicate iron deficiency 1
Other Conditions
- Hemolytic anemias
- Thalassemias
- Drug-induced ineffective erythropoiesis (e.g., chemotherapy agents) 3
- Advanced malignancy 4
Management Strategy
For Confirmed MDS
Risk stratification using the International Prognostic Scoring System-Revised (IPSS-R)
- Based on cytogenetics, blast percentage, and cytopenias
Treatment based on risk category:
Low-risk MDS:
- Erythropoiesis-stimulating agents if erythropoietin level <500 mU/mL
- Red blood cell transfusions for symptomatic anemia
- Iron chelation therapy for transfusion-dependent patients
High-risk MDS:
For Other Diagnoses
- Treat the underlying cause (iron deficiency, vitamin deficiencies, etc.)
- For pyruvate kinase deficiency: supportive care with transfusions, splenectomy in severe cases, monitoring for complications like iron overload and gallstones 1
Monitoring and Follow-up
- Regular complete blood counts
- Periodic bone marrow examinations for MDS patients to monitor disease progression
- Monitor for iron overload in transfusion-dependent patients
- Surveillance for transformation to acute myeloid leukemia in MDS patients
Pitfalls and Caveats
- Burr cells (echinocytes) can be artifactual due to prolonged storage of blood samples or high EDTA concentration
- Anisocytosis and poikilocytosis are nonspecific findings and can be seen in various hematologic disorders
- MDS diagnosis requires exclusion of other causes of cytopenias and dysplasia, including vitamin deficiencies, medications, toxins, and other hematologic disorders
- Cytogenetic abnormalities are crucial for diagnosis and prognosis but may be absent in up to 20% of MDS cases 1
- Splenectomy should be approached with caution in hematologic disorders due to risk of thrombotic complications 1