What is the evaluation and management approach for a patient with teardrop cells, elliptocytes, target cells, and anisocytosis on CDC (Centers for Disease Control and Prevention) morphology results?

Evaluation and Management of Mixed RBC Morphology Abnormalities

Immediate Diagnostic Priority

The combination of teardrop cells, elliptocytes, target cells, and anisocytosis requires urgent bone marrow examination to rule out myelodysplastic syndrome (MDS) or myelofibrosis, as these morphologic abnormalities represent dysplastic erythropoiesis and cannot be adequately assessed by peripheral smear alone. 1, 2

Systematic Diagnostic Approach

Essential Initial Laboratory Workup

Complete the following tests immediately to narrow the differential diagnosis:

• Complete blood count with differential including WBC count, hemoglobin, platelet count, and RBC indices (MCV, MCH, MCHC) 3, 2
• Reticulocyte count with corrected reticulocyte index to distinguish production versus destruction anemia 2
• Iron studies (serum iron, TIBC, transferrin saturation, ferritin) to evaluate for iron deficiency, thalassemia, or iron overload 1, 2
• Vitamin B12 and RBC folate levels since severe B12 deficiency can cause teardrop cells and anisocytosis 1, 4
• LDH, bilirubin, and haptoglobin to assess for hemolysis 3

Critical Morphologic Pattern Recognition

Your specific morphology pattern suggests three primary diagnostic considerations:

1. Myelodysplastic syndrome - The combination of anisocytosis with multiple poikilocyte types (teardrops, targets) indicates dysplastic erythropoiesis 1, 2, 5
2. Myelofibrosis - Teardrop cells are the characteristic finding, though other causes must be excluded 4
3. Severe nutritional deficiency - B12 deficiency can produce teardrops and marked anisocytosis 4

Mandatory Bone Marrow Evaluation

Proceed with bone marrow examination including:

• Bone marrow aspirate and biopsy with Prussian blue stain for iron to evaluate dysplasia, blast percentage, cellularity, and ringed sideroblasts 1, 3
• Cytogenetic analysis which is of major prognostic importance for MDS 1, 3
• Reticulin staining to assess for bone marrow fibrosis 1
• Flow cytometry to determine CD34+ blast percentage and evaluate for paroxysmal nocturnal hemoglobinuria (PNH) clone 1, 6

Note that flow cytometry blast estimates do not replace morphologic blast percentage by an experienced hematopathologist for prognostic purposes. 1

Additional Specialized Testing Based on Initial Results

If bone marrow shows dysplasia or hypoplasia:

• PNH screening and HLA-DR15 testing for young patients with normal cytogenetics and hypoplastic features who may respond to immunosuppressive therapy 1
• FISH, SNP array, and mutation analysis if cytogenetics are normal but dysplasia is present 3

If initial workup is inconclusive:

• Repeat bone marrow examination after 6 months of observation for patients with mild cytopenia, normal karyotype, and minimal dysplasia before confirming MDS diagnosis 3, 2

Critical Diagnostic Pitfalls to Avoid

Do not rely solely on automated CBC parameters - Visual peripheral smear review by an experienced observer is mandatory and cannot be replaced by automated indices 2

Do not overlook subtle dysplasia - Dysplastic features including hypogranulation of granulocytes, basophilic stippling, and giant platelets may be subtle and require careful examination 2

Document timing of recent transfusions - Donor RBC admixture interferes with accurate morphology assessment 2

Consider hereditary conditions - Elliptocytes can indicate hereditary elliptocytosis, particularly if family history is present, though this typically does not present with the mixed morphology pattern described 7

Management Framework

Treatment must be determined by the underlying diagnosis:

• If MDS is confirmed, refer immediately to a center with specific hematologic expertise for risk stratification using blast percentage, cytogenetics, and clinical factors 1, 3, 5
• If nutritional deficiency is identified, initiate appropriate replacement therapy while monitoring for improvement in morphology 4
• If myelofibrosis is diagnosed, hematology referral for consideration of JAK inhibitors or transplant evaluation 1

All patients require regular blood count monitoring regardless of diagnosis. 3