Understanding "2+A" Grading on Peripheral Blood Smear
The "2+A" notation on a peripheral blood smear indicates a semi-quantitative grading system where "2+" represents moderate numbers of abnormal red blood cells (typically 11-50 cells per 1000 RBCs or 3-10 cells per high-power field), and "A" likely refers to acanthocytes specifically, though standardized grading terminology varies between laboratories.
RBC Morphology Grading Scale
The semi-quantitative grading system for RBC abnormalities typically follows this pattern 1, 2:
- 1+ = Few abnormal cells (1-10 per 1000 RBCs or 1-2 per HPF)
- 2+ = Moderate numbers (11-50 per 1000 RBCs or 3-10 per HPF)
- 3+ = Many abnormal cells (>50 per 1000 RBCs or >10 per HPF)
- 4+ = Marked increase in abnormal cells
Clinical Significance of Your Findings
Burr Cells (Echinocytes) and Acanthocytes
The presence of 2+ burr cells and acanthocytes together with decreased platelets suggests you should systematically evaluate for:
- Liver disease - Acanthocytes are particularly associated with advanced liver cirrhosis and alcoholic liver disease 1, 3
- Pyruvate kinase deficiency - Can show 3-30% echinocytes, especially post-splenectomy, though RBC morphology is usually unremarkable 4
- Uremia/renal disease - Burr cells are classic findings
- Microangiopathic hemolytic anemia - Though schistocytes would be more prominent 1
- Hypersplenism - Can cause both RBC morphology changes and thrombocytopenia 3
Ovalocytes (Elliptocytes)
The presence of ovalocytes alongside other morphologic abnormalities is less specific but may indicate 4:
- Hereditary elliptocytosis (if predominant finding)
- Myelodysplastic syndromes - Can show anisocytosis and poikilocytosis 5, 6
- Megaloblastic anemia - Check B12 and folate levels 5
Decreased Platelet Estimate: Critical Differential
The combination of abnormal RBC morphology with thrombocytopenia requires immediate evaluation to exclude:
Primary Considerations
- Immune thrombocytopenia (ITP) - Should show isolated thrombocytopenia with otherwise normal CBC; peripheral smear evaluation by qualified hematologist/pathologist is paramount 1, 2
- Thrombotic thrombocytopenic purpura (TTP) - Look specifically for schistocytes on smear 1
- Liver disease with portal hypertension - Hypersplenism causes sequestration 1, 3
- Myelodysplastic syndrome - Requires bone marrow examination if dysplasia in multiple lineages 5, 6
- HIV/HCV infection - Can present with thrombocytopenia and RBC abnormalities 1
Essential Next Steps
You must obtain:
- Complete blood count with reticulocyte count - To assess for hemolysis vs. production defect 1, 5
- Comprehensive metabolic panel - Liver and kidney function 1, 5
- LDH, haptoglobin, indirect bilirubin - Markers of hemolysis 4
- Direct antiglobulin test (DAT) - Exclude immune-mediated hemolysis 4
- Peripheral smear review by hematopathologist - Essential for accurate diagnosis 1, 2
If anemia is present disproportionate to bleeding history, or if constitutional symptoms exist (fever, weight loss, lymphadenopathy), bone marrow examination should be strongly considered 1, 5, 6.
Common Pitfalls to Avoid
- Pseudo-thrombocytopenia - EDTA-dependent platelet clumping must be excluded by examining smear or repeating in citrate tube 1
- Artifact vs. true morphology - Burr cells can be artifactual from prolonged storage or improper slide preparation 4
- Missing schistocytes - If present, TTP/HUS becomes urgent consideration requiring immediate plasma exchange 1
- Overlooking medication history - Many drugs cause thrombocytopenia and RBC changes 1
- Failing to assess spleen size - Moderate/massive splenomegaly suggests alternative diagnosis to ITP 1
Laboratory Reporting Considerations
Modern automated systems (like CellaVision) may increase sensitivity for detecting low-percentage abnormal cells but can have high false-positive rates - manual review by experienced technologist remains essential 7.