Evaluation of Normal Reference Range of Schistocytes and Burr Cells in Healthy Adults
Authors: Ahmed Mashrafi , Patel Ashok R. 
Published: October 2019

Abstract
Introduction:
Schistocytes are split red blood cells that indicate microangiopathic hemolytic anemia. Their presence in a peripheral smear is the hallmark for diagnosing thrombotic thrombocytopenic purpura (TTP). Schistocytes may also be seen in healthy individuals and in patients with other diseases such as preeclampsia, eclampsia, chronic renal failure, solid organ or bone marrow transplantation, and diabetic microangiopathy as well as in patients with a prosthetic heart valve. Burr cells (echinocytes) are red blood cells with short, evenly spaced spicules and preserved central pallor that is usually artifactual (observed in uremia and liver disease). There has been no clear definition of a reference range for schistocytes or burr cells in normal individuals and among patients with various diseases. A previous study by Burns et al. included only 40 normal individuals to analyze the presence of schistocytes. In this study, we analyzed peripheral smears of 148 normal individuals to detect the normal reference range of schistocytes and burr cells in healthy adults and also attempted to determine the number of RBCs that need to be evaluated to consider the evaluation satisfactory.
Method:
We evaluated 148 peripheral blood smears of blood samples obtained from apparently healthy ambulatory adults (>18 years of age) with normal hemoglobin to determine the presence of schistocytes and burr cells.
Result:
Schistocytes were observed in approximately 78% of normal individuals with a mean of 0.15% of all RBCs. This finding is different from that of a previous study by Burns et al. (3) where schistocytes were observed in 58% of normal individual. Burr cell were observed in 77% of normal individual with a mean of 0.051% of all RBCs.
Table 1. Analysis of collected data for schistocytes RBC Count Mean Std. Deviation 95% CI (predicted values) 1000 1.73 1.26 1.51-1.93 2000 1.92 1.56 1.74-2.14 3000 1.59 1.26 1.39-1.80 4000 1.17 0.97 0.97-1.37 5000 1.26 1.10 1.06-1.46 Total 1.54 1.28
Table 2. Analysis of collected data for burr cells RBC Count Mean Std. Deviation 95% CI (predicted values) 1000 0.86 0.87 0.75-0.98 2000 0.34 0.50 0.23-0.45 3000 0.59 0.79 0.48-0.70 4000 0.32 0.69 0.20-0.43 5000 0.44 0.56 0.33-0.553 Total 0.51 0.72
Discussion:
TTP is an acute hematologic disorder involving different organ systems. The main pathophysiology of the disease is microvascular thrombosis due to increased platelet aggregation resulting in mechanical damage to erythrocytes. The diagnosis of TTP is predominantly based on characteristic clinical and laboratory findings. Therefore, observing schistocytes on peripheral smear is one of the key findings in the diagnostic process. A schistocyte is a fragmented erythrocyte characteristic of hemolysis or cell fragmentation. There is no clear definition of its appearance, shape, or size. Schistocyte recognition in the peripheral smear is largely based on clinician experience. Its mere presence is not exclusive of any pathological conditions only because it can also be observed in peripheral smears of a healthy patient. In the study by Burns et al., schistocytes were found in all patients with a mechanical heart valve, in 93% of patients with chronic renal failure, and in 58% of normal individuals. This finding is significantly different from that of our study where schistocytes were present in 87% of normal individuals. The reason of such a difference may be the extensive evaluation of each peripheral smear with the analysis of at least 5000 cells on each slide. Burr cells, also known as echinocytes, have a speculated border over the entire cell surface. Burr cells are commonly found in both end-stage renal disease and liver disease. In our study, Burr cells were found in 80% of healthy individuals although the numbers of cells are very small. One of the key findings in our analysis is determining the successful evaluation of peripheral smears for these two morphological variants of RBCs. Our data show that there is no significant change in the variation of the presence of schistocytes if 3000 erythrocytes are evaluated in a peripheral smear. For Burr cells, the analysis of 1000 erythrocytes in a high-power field appears sufficient. However, the drawback is that it is extremely time consuming to manually count such high numbers of RBCs and thus, the chance of an error is quite high.

Disclosures
No relevant conflicts of interest to declare.