At what percentage of total red blood cell (RBC) count are schistocytes considered significant?

Significance of Schistocytes in Clinical Practice

Definition and Threshold for Significance

Schistocytes are considered significant when they represent >1% of red blood cells on peripheral blood smear examination, which is suspicious for thrombotic microangiopathy (TMA). 1

• The International Council for Standardization in Hematology (ICSH) recommends a reference range of ≤1% schistocytes for healthy adults and full-term neonates 1
• For preterm infants, a higher normal threshold of ≤5% is recommended 1
• While the presence of schistocytes >1% raises suspicion for TMA, this finding should be interpreted in clinical context as other conditions can also present with elevated schistocyte counts 2, 3

Clinical Significance and Interpretation

• In thrombotic microangiopathies (TMAs), schistocytes are consistently ≥1% with a mean of 3.44±1.84% 3
• The presence of schistocytes >1% is a robust cytomorphological threshold that favors a diagnosis of TMA, but absence of schistocytes should not exclude an earlier diagnosis of TMA due to the test's low sensitivity 2
• Schistocytes should be considered clinically meaningful if they represent the main morphological abnormality in the peripheral blood smear 4

Conditions Associated with Elevated Schistocytes

Schistocytes ≥1% can be observed in various conditions:

• Thrombotic microangiopathies (TTP/HUS) 2, 3
• Renal failure (both acute and chronic) 4, 3
• Hemoglobinopathies 3
• Preterm infants 1
• Metastatic carcinoma 4
• Severe infections and sepsis 4, 5
• Hematologic malignancies (median 1.20%) 4
• Disseminated intravascular coagulation (DIC), though usually <0.5% 5
• Promyelocytic leukemia, pregnancy complications, and severe infections may show higher percentages (≥1%) 5

Diagnostic Approach

• Schistocyte evaluation should follow ICSH standardized procedures to reduce observer bias 3
• Schistocytes should be counted using a 100× objective (high-power field) with approximately 100 red blood cells per field 6
• A grading scale can be used: rare (1 schistocyte per every other field), 1+ (1-5%), 2+ (6-15%), and 3+ (>15%) 6
• Automated fragment red cell count (FRC) from hematology analyzers can serve as a valuable screening tool, particularly for excluding the presence of schistocytes when FRC is negative 1

Clinical Pearls and Caveats

• Residual schistocytosis (presence of schistocytes when platelet counts normalize) is common (35.6%) in TTP/HUS patients but does not predict relapse 6
• In conditions other than TMA, schistocytes are usually detected together with other red blood cell morphologic changes 4
• In DIC, schistocytes are frequently observed but usually at low percentages (mean 0.33±0.38%), often within or close to the reference range (<0.5%) 5
• For TTP/HUS diagnosis, schistocytes should be evaluated alongside other criteria including thrombocytopenia, microangiopathic hemolytic anemia, elevated LDH levels, and reduced haptoglobin levels 2
• Some experts recommend a higher threshold for schistocytes in thrombotic thrombocytopenic purpura to distinguish this hematological emergency from other conditions associated with ≥1% schistocytes 3

Laboratory Considerations

• Schistocyte evaluation should be performed on freshly collected peripheral blood samples 1
• Observer variability exists in schistocyte identification, with one study showing a correlation coefficient of 0.63 between morphologists 3
• Automated analyzers may underestimate schistocyte counts in patients with TMA 3
• False thrombocytopenia should be excluded by examining the peripheral blood smear before initiating investigations for true thrombocytopenia 7