What are schistocytes (fragmented red blood cells)?

From the Guidelines

The presence of schistocytes in a peripheral blood smear is a critical diagnostic finding that indicates microangiopathic hemolytic anemia, and further investigation is necessary to determine the underlying cause, as recommended by the most recent guidelines 1. When schistocytes are detected, a comprehensive diagnostic work-up should be performed, including a history and physical examination, CBC with indices, blood smear morphology, serum creatinine, ADAMTS13, homocysteine or MMA, complement testing, and evaluation of reticulocyte count and mean corpuscular volume, as outlined in the guidelines 1. The diagnostic work-up should also include evaluation for infectious causes, nutritional causes of macrocytosis, pancreatic enzymes, and common drugs causing hemolysis, as well as direct antibody testing and evaluation for neurologic changes, as recommended by the guidelines 1. Common conditions associated with schistocytes include thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), disseminated intravascular coagulation (DIC), malignant hypertension, and mechanical heart valves. Laboratory findings that often accompany schistocytosis include decreased hemoglobin, elevated lactate dehydrogenase (LDH), decreased haptoglobin, and increased reticulocyte count, reflecting ongoing hemolysis, as noted in the guidelines 1. Treatment should focus on addressing the underlying cause rather than the schistocytes themselves, and the most recent guidelines should be consulted for the latest recommendations on management and treatment 1.

From the Research

Definition and Identification of Schistocytes

• Schistocytes are fragmented red blood cells produced by extrinsic mechanical damage within the circulation 2
• They are mainly observed in the setting of hemolytic anemias and particularly among the thrombotic microangiopathies 3
• The International Council for Standardization in Hematology (ICSH) has prepared specific recommendations to standardize schistocyte identification, enumeration, and reporting 2

Clinical Significance of Schistocytes

• The presence of schistocytes is an important criterion for the diagnosis of mechanical anemias 3
• Schistocytes are frequently observed in patients with microangiopathic hemolytic anemia (MAHA), metastatic carcinoma, sepsis, chronic renal failure, preterm infant, and infection 4
• A schistocyte count has a definite clinical value for the diagnosis of thrombotic microangiopathic anemia (TMA) in the absence of additional severe red cell shape abnormalities, with a confident threshold value of 1% 2

Measurement and Quantitation of Schistocytes

• The ICSH recommends a grading scale for schistocytes, with a threshold value of 1% for clinical significance 2
• Automated counting of RBC fragments is also recommended by the ICSH Working Group as a useful complement to the microscope 2
• However, the identification of schistocytes remains problematic due to variability of shape and nature of fragments, as well as subjectivity and heterogeneity in their morphological assessment 3

Schistocytes in Specific Diseases

• In thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), the presence of schistocytes is a key diagnostic criterion, but residual schistocytosis at the time of discontinuation of plasma exchange therapy is not predictive of relapse 5
• Schistocytes can be observed in various diseases other than TTP/HUS, and in these cases, schistocytes are usually detected together with other red blood cell morphologic changes 4
• TTP can occur without schistocytes on the peripheral blood smear, emphasizing the need to consider TTP-hemolytic uremic syndrome in the differential diagnosis, even in the absence of peripheral schistocytosis 6