What are schistocytes?

What Are Schistocytes

Schistocytes are fragmented red blood cells produced by mechanical damage within the circulation, appearing as helmet-shaped cells, small irregular triangular or crescent-shaped cells with pointed projections and lacking central pallor. 1

Morphological Identification

The International Council for Standardization in Haematology (ICSH) defines schistocytes based on specific positive morphological criteria:

• Helmet cells - the most characteristic form 1
• Small, irregular triangular or crescent-shaped cells with pointed projections 1
• Absence of central pallor distinguishing them from normal red cells 1
• Fragments result from extrinsic mechanical forces that physically shear red blood cells as they pass through damaged microvasculature 1

Clinical Significance and Diagnostic Thresholds

A schistocyte count ≥1% is considered clinically meaningful when schistocytes represent the main morphological abnormality on peripheral blood smear. 1 This threshold is critical because:

• Schistocytes above 1% can occur in various conditions including metastatic carcinoma, chronic renal failure, and mechanical heart valves 2
• The presence of schistocytes is a hallmark finding in thrombotic microangiopathic anemias, particularly thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) 2
• However, the absence of abundant schistocytes does not exclude thrombotic microangiopathy (TMA) due to low test sensitivity 2

A critical pitfall: Do not dismiss the diagnosis of TMA based on "rare" schistocytes alone, as low schistocyte counts can occur in early or evolving disease. 2

Quantification Method

The ICSH recommends standardized counting using a 100x objective (high power field with approximately 100 red blood cells per field): 1

• Count schistocytes per 1000 red blood cells, expressed as a percentage 3
• Grading scale: rare (1 per every other field), 1+ (1-5%), 2+ (6-15%), 3+ (>15%) 4
• Schistocyte counts should only be considered diagnostically significant when they represent the predominant morphological abnormality, not when accompanied by multiple other red cell shape changes 5, 1

Associated Clinical Conditions

Schistocytes appear in a broad spectrum of diseases beyond TTP/HUS:

• Microangiopathic hemolytic anemia (MAHA) - the primary association 5
• Malignant hypertension with thrombotic microangiopathy - typically shows only moderate thrombocytopenia and few schistocytes compared to TTP/HUS 6
• Metastatic carcinoma, sepsis, chronic renal failure 5
• Post-bone marrow transplantation - mild schistocytosis (0.1-4.3%) occurs in 99% of patients but has no clinical significance without other TMA features 3
• Hematologic malignancy, megaloblastic anemia, acute renal failure (median counts 1.20-1.70%) 5

In 169 of 170 cases with schistocyte counts ≤1%, other morphological changes were present, emphasizing that isolated schistocytosis is the key diagnostic finding. 5

Diagnostic Workup When Schistocytes Are Present

When schistocytes are detected, immediately order: 2

• ADAMTS13 activity level and inhibitor titer - most critical test 2
• Complete blood count with platelet count 2
• Lactate dehydrogenase (LDH) and haptoglobin 2
• Direct antiglobulin test (DAT) to exclude immune hemolysis 2
• Peripheral blood smear review by qualified hematologist 6
• Creatinine and urinalysis for hematuria/proteinuria 2

The triad defining TMA consists of non-immune microangiopathic hemolysis, thrombocytopenia, and organ involvement (typically renal). 2

Limitations and Context

Residual schistocytosis (present when platelet count normalizes) occurs in 35.6% of TTP/HUS patients at discontinuation of plasma exchange therapy but does not predict relapse. 4 This finding should not delay stopping treatment when other parameters have normalized. 4

Automated counting of red cell fragments is recommended as a useful complement with high negative predictive value, but requires further validation for quantitation. 1