The Clinical Significance of Schistocytes: A Prospective Evaluation of the International Council for Standardization in Hematology Schistocyte Guidelines

Abstract

Objective:The presence of ≥1% schistocytes on a peripheral blood smear (PBS) is an important criterion for the diagnosis of thrombotic microangiopathy (TMA). The reporting of schistocytes has been standardized by the International Council for Standardization in Hematology (ICSH). Despite the availability of guidelines, however, the assessment of schistocytes remains subjective. More recently, the automated fragmented red cell (FRC) parameter has been evaluated. However, local studies are not available.Materials and Methods:A prospective study was performed at the Charlotte Maxeke Johannesburg Academic Hospital in order to evaluate the ICSH recommendations for schistocyte measurement in 146 PBSs with schistocytes. Schistocytes were evaluated by microscopy and ADVIA 2120 automated hematology analyzers.Results:Schistocytes were frequently observed in patients with TMA (n=76), infection (n=20), hematologic malignancy (n=10), renal failure (n=5), and hemoglobinopathy (n=15), and in neonates (n=11). Schistocytes were ≥1% in all PBSs with TMA (n=76) with a mean of 3.44±1.84. Schistocytes of ≥1% were also observed in cases of renal failure and hemoglobinopathy, and in neonates. In these conditions, schistocytes were mainly observed in conjunction with moderate red blood cell changes. The agreement between two morphologists gave a correlation coefficient of 0.63 [confidence interval (CI): 0.52-0.75], while the correlation coefficient between the average of the morphologists and the FRC percentage was -1.97 (CI: -1.60 to -2.34). The ADVIA 2120 underestimated the schistocyte count in patients with TMA.Conclusion:Observer bias can be decreased by implementing the standardized procedures recommended by the ICSH. However, estimation of schistocytes by the ADVIA 2120 analyzer requires further evaluation as a screening tool. A higher threshold for schistocytes in thrombotic thrombocytopenic purpura is recommended to distinguish this hematological emergency from other conditions associated with ≥1% schistocytes.

Thrombotic Microangiopathy Score as a New Predictor for Neurologic Outcome in Patients Undergoing Targeted Temperature Management After Out-of-hospital Cardiac Arrest

“…Despite differences in the mechanisms of underlying DIC and TMA [33], several different conditions, such as atypical hemolytic uremic syndrome, DIC, and drug toxicities, can be also considered as different forms of TMA [34]. It is di cult to use the schistocyte count as a complete indicator for the initial diagnosis and con rmation of TMA and DIC [13]. Various conditions including severe infection, pregnancy, and leukemia frequently produce schistocytes [13,35].…”

“…It is di cult to use the schistocyte count as a complete indicator for the initial diagnosis and con rmation of TMA and DIC [13]. Various conditions including severe infection, pregnancy, and leukemia frequently produce schistocytes [13,35]. Nevertheless, the International Council for Standardization in Hematology (ICSH) guideline states that presence of > 1% schistocytes without other moderate changes in RBCs upon a peripheral blood smear can be considered as a critical criterion for the diagnosis of TMA [13].…”

“…The application of new biomarkers that easily and quickly predict the development of unfavorable neurologic outcome and mortality after post-resuscitation may improve the prognosis of patients by enabling innovative monitoring, early aggressive treatment, and therapeutic strategies [10][11][12]. Thrombotic microangiopathy (TMA) is characterized by three important elements including higher levels of lactate dehydrogenase, thrombocytopenia, and fragmented erythrocytes (schistocytes) [13]. Several critical conditions lead to the development of systemic endothelial injury in critically ill patients [14,15].…”

“…In endothelial injury, severe hemolysis from mechanical damage in the circulation occasionally produce schistocytes in turbulent areas of the microcirculation that are partly occluded by platelet aggregations [14,16]. The International Council for Standardization in Hematology (ICSH) Schistocyte Working Group recommended that the more than 1% schistocytes on a peripheral blood smear is an important criterion for identifying TMA [13]. Moreover, the occurrence of schistocytes in blood re ects a high risk of thrombocytopenia-associated multiple organ failure (TAMOF) [17].…”

Comparison between optical microscopy and the Sysmex XN‐3000 for schistocyte determination in patients suspected of having schistocytosis

“…Consistent with the recommendations of the Schistocyte Working Group of the International Council for Standardization in Haematology (ICSH), schistocytes were counted microscopically among 1000 RBCs (five oil fields) at 1000x magnification in optimal areas (where RBCs were appropriately separated from each other) of a peripheral blood smear, with May‐Grünwald‐Giemsa staining. The Sysmex XN‐3000 has slide‐making and slide‐staining functions, so 600 μL of blood was used to make one peripheral blood smear according to the manufacturer's protocol.…”