What does the presence of a few teardrop-shaped red blood cells on a Complete Blood Count (CBC) indicate in an adult or older adult patient?

Teardrop Cells on CBC: Clinical Significance

A few teardrop-shaped red blood cells (dacryocytes) on a CBC most commonly indicate myelodysplastic syndromes (MDS) as a sign of dysplasia, but can also signal primary myelofibrosis, autoimmune hemolytic anemia, or microangiopathic hemolytic anemia—requiring immediate evaluation of the complete clinical context, additional CBC parameters, and bone marrow examination if cytopenias or other dysplastic features are present. 1

Primary Differential Diagnosis

Myelodysplastic Syndromes (Most Common Context)

• Teardrop cells are explicitly listed as a sign of red cell dysplasia in MDS according to ESMO guidelines, appearing alongside other poikilocytes, ovalocytes, and fragmentocytes in the peripheral blood 1
• MDS typically presents with cytopenias (hemoglobin <11.0 g/dL, neutrophils <1500/mL, and/or platelets <100,000/mL) persisting for at least 4 months 1
• Look for additional dysplastic features that strengthen MDS diagnosis: basophilic stippling, nucleated erythroid precursors, pseudo-Pelger-Huet cells, giant platelets, anisocytosis, and polychromasia 1
• Bone marrow examination is mandatory when MDS is suspected, particularly in elderly patients with unexplained cytopenias and dysplastic peripheral blood features 1, 2

Primary Myelofibrosis

• Teardrop cells are a characteristic hallmark of myelofibrosis, traditionally reflecting altered marrow architecture 1, 3
• In prefibrotic PMF, expect few if any dacryocytes with no or mild leukoerythroblastosis and mild red blood cell poikilocytosis 1
• In overt fibrotic PMF, teardrop cells become more prominent alongside leukoerythroblastic blood picture, splenomegaly, and bone marrow reticulin/collagen fibrosis 3
• PMF features bone marrow hypercellularity with megakaryocytic proliferation and atypia (clustering, abnormally lobulated nuclei) 1

Hemolytic Anemias (Often Overlooked)

• Dacryocytes appear in 89-91% of autoimmune hemolytic anemia (AIHA) and microangiopathic hemolytic anemia (MAHA) cases, a frequently underrecognized finding 4
• In AIHA with splenomegaly and extramedullary hematopoiesis, teardrop cells can be striking in predominance and resolve with splenectomy or treatment 5
• Distinguish hemolytic causes by checking hemolysis markers: elevated LDH, low haptoglobin, elevated unconjugated bilirubin, elevated reticulocyte count 2

Diagnostic Algorithm

Step 1: Assess Complete Blood Count Parameters

• Check MCV: MDS typically shows macrocytic anemia, while iron deficiency (which can show pencil cells, not teardrops) shows microcytic anemia 2
• Evaluate for cytopenias: Presence of persistent cytopenias (>4 months) strongly suggests MDS over reactive processes 1
• Count reticulocytes: Low reticulocytes suggest inadequate marrow response (MDS, myelofibrosis); elevated reticulocytes indicate hemolysis or blood loss 2

Step 2: Examine Peripheral Blood Smear Thoroughly

• Quantify dysplastic features: Look for pseudo-Pelger-Huet cells, hypogranulation, giant platelets, basophilic stippling, nucleated RBCs 1
• Assess leukoerythroblastosis: Presence of immature myeloid and erythroid precursors suggests myelofibrosis or marrow infiltration 1
• Evaluate other poikilocytes: Schistocytes suggest MAHA; spherocytes suggest AIHA 4

Step 3: Obtain Targeted Laboratory Studies

• Iron studies immediately: Serum ferritin, transferrin saturation, serum iron to exclude iron deficiency 2
• Hemolysis workup if indicated: Haptoglobin, LDH, unconjugated bilirubin, direct antiglobulin test (DAT) 2, 4
• Vitamin B12 and folate levels: To exclude megaloblastic anemia as alternative cause of dysplasia 2

Step 4: Proceed to Bone Marrow Examination When Indicated

• Mandatory for suspected MDS: Perform bone marrow aspirate with cytology, cytochemistry, immunophenotyping, and trephine biopsy 1
• Cytogenetic analysis is mandatory: At least 20 metaphases evaluated to detect MDS-related abnormalities (del(5q), -7, del(7q), etc.) 1
• Assess for fibrosis: Reticulin and collagen staining distinguishes myelofibrosis from MDS 1
• Evaluate dysplasia quantitatively: >10% dysplastic cells in a lineage qualifies as significant dysplasia for MDS diagnosis 1

Critical Clinical Pitfalls

Common Misinterpretations

• Do not assume myelofibrosis exclusively: While traditionally associated with myelofibrosis, teardrop cells are now recognized as a common dysplastic feature in MDS and hemolytic anemias 1, 4
• "Few" teardrops still require investigation: Even occasional teardrop cells warrant complete evaluation if accompanied by cytopenias or other dysplastic features 1
• Splenomegaly with teardrops suggests multiple etiologies: Consider AIHA with extramedullary hematopoiesis, not just myelofibrosis 5

Reversibility Considerations

• Teardrop cells can be reversible with effective treatment: In myelofibrosis, chemotherapy can reduce or eliminate dacryocytes 6
• In AIHA, splenectomy or resolution of splenomegaly leads to disappearance of teardrop cells 5
• This reversibility underscores that teardrops reflect active pathologic processes requiring treatment, not just static marrow architecture 5, 6

Age-Related Considerations

• In elderly patients, MDS becomes increasingly likely with unexplained cytopenias and dysplastic features including teardrops 1, 2
• Pediatric cases with teardrops are rare but can represent agnogenic myeloid metaplasia (chronic myelofibrosis), presenting with splenomegaly and leukoerythroblastosis 7