What Are Schistocytes?
Schistocytes are fragmented red blood cells (RBCs) produced by mechanical damage within the circulation, appearing as helmet cells, small irregular triangular or crescent-shaped cells with pointed projections and lack of central pallor. 1
Morphologic Characteristics
Schistocytes can be identified on peripheral blood smear by specific morphologic features:
- Helmet cells are the most characteristic form 1
- Small, irregular triangular or crescent-shaped cells with pointed projections 1
- Absence of central pallor distinguishes them from normal RBCs 1
- Also described as burr cells or helmet cells in diagnostic criteria 2, 3
Clinical Significance
The presence of schistocytes on peripheral blood smear is the morphologic hallmark of thrombotic microangiopathic anemias (TMA), particularly thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). 2, 4
Diagnostic Threshold
- A schistocyte count >1% strongly suggests TMA in the absence of other causes 1, 4
- In TTP patients, schistocyte counts range from 1.0% to 18.4% (mean 8.35%) 4
- In normal individuals, schistocytes comprise <0.5% of RBCs when present 4
Critical Diagnostic Context
The presence of schistocytes on blood smear is critical for diagnosis of TMA conditions, and evaluation by a qualified hematologist or pathologist is paramount. 2
- Schistocytes indicate microangiopathic hemolytic anemia when accompanied by elevated LDH, decreased haptoglobin, and negative direct Coombs test 5, 3
- The absence of abundant schistocytes does not exclude TMA due to low test sensitivity 5
Pathophysiology
Schistocytes form through mechanical fragmentation as RBCs pass through damaged small blood vessels containing platelet-rich thrombi and fibrin networks. 3
- Endothelial damage leads to coagulation activation and fibrin formation 3
- RBCs become trapped and destroyed in the fibrin network 3
- This mechanical damage occurs within the circulation, distinguishing it from other causes of RBC abnormalities 1
Conditions Associated with Schistocytes
Primary Thrombotic Microangiopathies
- Thrombotic thrombocytopenic purpura (TTP) - characterized by the pentad of microangiopathic hemolytic anemia, thrombocytopenia, fever, neurological abnormalities, and renal dysfunction 3
- Hemolytic uremic syndrome (HUS) - typically follows acute gastrointestinal illness with predominant renal involvement 2, 3
Secondary Causes (Lower Schistocyte Counts)
- Mechanical heart valves - schistocytes comprise approximately 0.18% of RBCs 4
- Chronic renal failure - schistocytes comprise approximately 0.2% of RBCs 4
- Preeclampsia - schistocytes comprise approximately 0.25% of RBCs 4
- Metastatic carcinoma 5
Clinical Pitfalls
Do not dismiss the diagnosis of TMA based on "rare" schistocytes alone, as low schistocyte counts can occur in early or evolving TMA. 5
- Residual schistocytosis (presence of schistocytes after treatment) occurs in 35.6% of TTP/HUS patients when platelet counts normalize and does not predict relapse 6
- Schistocytes are found in 58% of normal individuals but always comprise <0.5% of the RBC population 4
Recommended Counting Method
Schistocytes should be counted using a 100x objective (high power field) with approximately 100 red blood cells per field, with a confident diagnostic threshold of 1%. 1, 4