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Schistocytes or schizocytes are defined as circulating red blood cell fragments. Detection of schistocytes is an important clue for the diagnosis of thrombotic microangiopathy (TMA), which includes both thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS). Other causes of schistocyte formation include structural abnormalities of heart and great vessels, malfunctioning prosthetic valve, HELLP syndrome, malignant hypertension, and metastatic carcinoma. A more recent indication for schistocyte counting is monitoring bone marrow transplant patients for the onset of TMA, which is a frequent and severe complication. Non-TMA causes of red blood cell fragmentation include red blood cell membrane defects, thalassemia, megaloblastic anemia, primary myelofibrosis, and thermal injury. The red blood cell fragments in these cases show high variability in shapes and marked aniso-poikilocytosis which are not specific for the diagnosis of TMA.

Poorly defined morphological criteria for identification and enumeration of schistocytes have adversely affected treatment and clinical outcome of TMA in the past. In 2008, the Schistocyte Working Group (SWG) of the Internal Council for Standardization in Hematology undertook the task of preparing scientific recommendations to standardize schistocyte identification, enumeration, and reporting. The overall final recommendations of SWG were published in 2011 and are available at Briefly the recommendations are:

  1. The morphological criteria required for identification of schistocytes includes cells smaller than intact red blood cells and have shapes with sharp angles and straight borders, small crescents, helmet cells, keratocytes, and microspherocytes.
  2. A schistocyte count should be considered clinically meaningful if schistocytes represent the main morphological red blood cell abnormality in the smear.
  3. In adults, a schistocyte percentage above 1% should be considered as a robust cytomorphological indication favoring TMA. In cases where the clinical suspicion of TMA is high but schistocytes are absent, blood smear screening for schistocytes should be repeated daily because their appearance may be delayed for several days.
  4. For diagnosis of transplant associated TMA, schistocyte threshold of 4% is recommended together with thrombocytopenia, increased lactate dehydrogenase, decreased hemoglobin concentration, and decreased haptoglobin.
  5. Automated hematology analyzers flag for fragmented red cells and some of these analyzers can also provide an automated fragmented red cell count which can be used for screening test and follow-up.
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