What is the significance of peripheral blood smear findings of polychromasia, anisocytosis, and a few poikilocytes in a patient who has become anemic?

Significance of Peripheral Blood Smear Findings in New-Onset Anemia

These blood smear findings—polychromasia, anisocytosis (likely what "anisochromasia" refers to), and a few poikilocytes—indicate an active bone marrow response to anemia and suggest the need to determine whether this represents appropriate regeneration (hemolysis, bleeding) versus dysplastic changes (myelodysplastic syndrome, nutritional deficiency) or early microangiopathic process.

Interpretation of Individual Findings

Polychromasia

• Polychromasia reflects the presence of young red blood cells (reticulocytes) and indicates bone marrow regenerative activity in response to anemia 1
• This finding suggests the bone marrow is attempting to compensate for red cell loss or destruction 1
• The presence of polychromasia is a more accurate indicator of regenerative anemia than other erythrocyte indices, though it should be confirmed with an actual reticulocyte count 2

Anisocytosis (Variable Cell Size)

• Anisocytosis—variation in red blood cell size—is a nonspecific finding that can occur in both regenerative anemias (due to young cells) and dysplastic conditions 1
• In myelodysplastic syndromes, anisocytosis is listed as a characteristic peripheral blood finding of erythroid dysplasia 1
• When combined with polychromasia, anisocytosis may simply reflect the mixture of mature and immature red cells in a regenerative process 3

A Few Poikilocytes (Abnormal Cell Shapes)

• Occasional nonspecific poikilocytes can be found in most normal blood smears, but their clinical significance depends on the specific type and quantity present 4
• In myelodysplastic syndromes, poikilocytosis is recognized as a sign of dysplasia, along with other morphologic abnormalities 1
• The presence of "a few" poikilocytes is relatively nonspecific and requires identification of the specific cell types (schistocytes, teardrop cells, target cells, etc.) to guide diagnosis 3, 4

Critical Diagnostic Algorithm

Step 1: Obtain Reticulocyte Count Immediately

• A reticulocyte count is mandatory to distinguish regenerative from hypoproliferative anemia 1
• An elevated reticulocyte count (>65,000/μL or corrected reticulocyte index >2%) confirms appropriate bone marrow response 2
• A low or inappropriately normal reticulocyte count despite anemia suggests bone marrow failure, nutritional deficiency, or myelodysplastic syndrome 1

Step 2: Examine the Specific Poikilocyte Types

• Request that the laboratory specifically identify which poikilocytes are present, as this dramatically changes the differential diagnosis 5, 3
• If schistocytes are present (even in small numbers), immediately evaluate for thrombotic microangiopathy (TMA) by ordering ADAMTS13 activity, LDH, haptoglobin, direct antiglobulin test, platelet count, and creatinine 5
• Do not dismiss TMA based on "rare" or "few" schistocytes alone, as low schistocyte counts can occur in early or evolving disease 5
• If teardrop cells predominate, consider myelofibrosis or infiltrative marrow process 4

Step 3: Assess MCV and Additional Indices

• Determine if the anemia is microcytic (<80 fL), normocytic (80-100 fL), or macrocytic (>100 fL) to guide further workup 1
• Normocytic anemia with polychromasia and elevated reticulocytes suggests hemolysis or acute blood loss 1
• Macrocytic anemia requires evaluation for vitamin B12 and folate deficiency, which can present with poikilocytosis and anisocytosis 6

Step 4: Hemolysis Workup if Regenerative

• If reticulocyte count is elevated, obtain LDH, haptoglobin, indirect bilirubin, and direct antiglobulin test to confirm hemolysis and determine if immune-mediated 5, 7
• Review for clinical signs of hemolysis including jaundice, dark urine, and splenomegaly 1

Step 5: Consider Myelodysplastic Syndrome if Hypoproliferative

• If reticulocyte count is inappropriately low and dysplastic features are present, bone marrow aspiration and biopsy with cytogenetics are mandatory to evaluate for MDS 1
• In MDS, dysplasia must be present in >10% of cells in at least one lineage to qualify as significant 1
• Peripheral blood findings alone are insufficient to diagnose MDS; bone marrow examination is required 1

Common Pitfalls to Avoid

• Do not assume polychromasia alone confirms adequate regeneration without obtaining an actual reticulocyte count, as visual estimation is unreliable 2
• Do not overlook early TMA or microangiopathic hemolytic anemia based solely on "a few" poikilocytes if they include schistocytes 5, 8
• Do not delay urgent evaluation for TTP/HUS if clinical suspicion is high, even while awaiting confirmatory testing 5
• In severe cases with schistocytes, thrombocytopenia, and organ dysfunction, consider pseudo-TTP from severe B12 deficiency, which can mimic TMA but responds dramatically to vitamin replacement 6

Immediate Next Steps

• Order reticulocyte count, LDH, haptoglobin, and direct antiglobulin test 5, 7
• Request specific identification of poikilocyte types from the laboratory 3
• Obtain comprehensive metabolic panel to assess renal function 5, 7
• If schistocytes are confirmed, add ADAMTS13 activity level and platelet count urgently 5
• Consider bone marrow examination if reticulocyte count is inappropriately low for the degree of anemia 1