The presence of schistocytes can be responsible for spurious thrombocytosis and spuriously low red blood count (RBC). The hemoglobin concentration will be correct (as the method usually used, destroys the red cells and converts a substantial proportion of the hemoglobin to a stable pigment) but mean corpuscular hemoglobin (MCH) is falsely high. The platelets and RBC histograms of the full blood count analyzers play an important role in the identification of schistocytes and must be carefully analyzed before reporting the previously full blood count parameters. In patients in ECMO, where can be expected the presence of a small number of schistocytes, this evaluation is particularly important to avoid wrong clinical decisions.

Schistocytes are fragmented red blood cells produced as a result of mechanical damage to erythrocytes, usually due to microangiopathic thrombotic diseases or mechanical factors. The early laboratory detection of schistocytes has a critical impact on the timely diagnosis, effective treatment, and positive prognosis of diseases such as thrombocytopenic purpura and hemolytic uremic syndrome. Due to the rapid development of science and technology, laboratory hematology has also advanced. The accuracy and efficiency of tests performed by fully automated hematology analyzers and fully automated morphology analyzers have been considerably improved. In recent years, substantial improvements in computing power and machine learning (ML) algorithm development have dramatically extended the limits of the potential of autonomous machines. The rapid development of machine learning and artificial intelligence (AI) has led to the iteration and upgrade of automated detection of schistocytes. However, along with significantly facilitated operation processes, AI has brought challenges. This review summarizes the progress in laboratory schistocyte detection, the relationship between schistocytes and clinical diseases, and the progress of AI in the detection of schistocytes. In addition, current challenges and possible solutions are discussed, as well as the great potential of AI techniques for schistocyte testing in peripheral blood.

Red blood cells (RBCs) start to break down early in hemolytic anemia, which can be chronic or life-threatening. It should be considered while determining if normocytic or macrocytic anemia is present. Hemolysis in the reticuloendothelial system may happen intravascularly, extravascularly, or both. It accounts for a broad spectrum of laboratory and clinical situations, both physiological and pathological. Whenever the frequency of RBC breakdown is rapid enough to lower hemoglobin levels below the normal range, hemolytic anemia occurs. Microangiopathic hemolytic anemia (MAHA) is a term used to describe non-immune hemolysis induced by intravascular RBC fragmentation caused by substances in the tiny blood arteries that generate schistocytes in the peripheral circulation. Microvasculature abnormalities, such as small arterioles and capillaries, are usually involved. Furthermore, MAHA can also be brought on by intravascular devices like a prosthetic heart valve or assistive technologies. Poor deformity results in entrapment, phagocytosis, antibody-mediated elimination through phagocytosis or direct complement activation, fragmentation brought about by microthrombi or acute mechanical stress, oxidation, or spontaneous cellular death. Hemolysis may cause acute anemia, jaundice, hematuria, dyspnea, tiredness, tachycardia, and possibly hypotension. This article aims to synthesize existing research, identify therapeutic strategies, and provide insights into current and emerging approaches for managing this complex hematological disorder.

Thrombotic thrombocytopenic purpura (TTP) and vitamin B12 deficiency can share similar symptoms but require different treatment approaches. TTP is a blood disorder with a high mortality rate requiring immediate plasmapheresis treatment. On the other hand, vitamin B12 deficiency usually presents with anemia, low platelet counts, jaundice, and signs of disrupted red blood cell breakdown, resembling a condition called microangiopathic hemolytic anemia. Vitamin B12 deficiency can sometimes lead to or mimic pseudo-thrombotic microangiopathy (pseudo-TMA), a rare occurrence. Pseudo-TMA manifests as microangiopathic hemolytic anemia and thrombocytopenia and is characterized by schistocytes in a peripheral blood smear. Differentiating TTP cases from pseudo-TMA cases is essential and should be done promptly. The etiology, treatments, and prognosis of these two conditions differ and can be fatal if not identified and managed. We present a case that emphasizes the need for familiarity with TTP-like conditions, the use of ADAMTS13 as a diagnostic tool, prompt and accurate treatment decision-making, the complexities of therapeutic plasma exchange, and the importance of excluding an enzyme inhibitor or mutator as the cause of TTP or TTP-like cases. Lack of knowledge can lead to erroneous diagnoses, resulting in unnecessary treatments or delayed life-saving interventions.

Background  Thrombotic microangiopathy encompasses a wide range of conditions, of which thrombotic thrombocytopenic purpura being a medical emergency requires prompt intervention, with schistocytes being a reliable morphological indicator of microvascular injury. However, there are conditions other than thrombotic microangiopathic anemia where schistocytes can be seen in large numbers. These nonthrombotic microangiopathic conditions are broadly grouped under cytoskeletal abnormalities, mechanical damage, and thermal injuries. Automated methods in schistocyte evaluation have shown varied reproducibility requiring manual identification. International Council for Standardization in Hematology (ICSH) recommends standardized morphological criteria and quantitative assessment as a percentage after counting at least 1,000 red blood cells in optimal areas of smear to reduce interobserver variability. Objectives  The aim of this study was to evaluate and quantitate schistocytes in thrombotic microangiopathic and nonthrombotic microangiopathic groups using ICSH guidelines and to evaluate interobserver reproducibility of manual schistocyte count. Materials and Methods  Overall, 157 peripheral blood smears showing schistocytes were studied by two independent observers using ICSH recommendations on light microscopy. The hematological findings were correlated with clinical diagnosis and other relevant investigations. Results  Schistocytes were observed in five cases of thrombotic microangiopathic anemia and 152 cases of nonthrombotic microangiopathic anemia. Schistocyte count in thrombotic microangiopathic anemia and nonthrombotic microangiopathic anemia groups with mean (±standard deviation) value was 2.28 ± 2.65% and 0.76 ± 0.67%, respectively ( p  < 0.001). The correlation coefficient between the two observers was 0.59 (confidence interval = 0.966-1.346) showing an excellent agreement on the reproducibility of schistocytes by application of ICSH guidelines. Conclusion  Percentage of schistocytes more than 1% is a robust morphological indicator for diagnosis of thrombotic microangiopathic anemia in adults. Strict application of ICSH guidelines reduces interobserver bias.

UNASSIGNED: The objective of this study was to highlight the role of the clinical laboratory and the relevance of reporting the case immediately to the unit of hematology for the diagnosis and early administration of treatment in the presence of such an urgent hematologic disease as thrombotic thrombocytopenic purpura (TTP).
UNASSIGNED: An elderly patient was referred to the emergency department of our hospital by his general practitioner for speech difficulty, facial asymmetry and weakness in the upper limb. Stroke code was activated. However, laboratory findings (anemia, thrombocytopenia, elevated creatinine, total bilirubin and LDH, negative direct Coombs test) and presence of schistocytes in the peripheral blood smear test were consistent with a completely different diagnosis: TTP thrombotic microangiopathy.
UNASSIGNED: The first diagnostic approach of left hemispheric stroke was not confirmed in the laboratory, with findings of nonautoimmune hemolytic anemia, thrombocytopenia without apparent cause and presence of schistocytes. We should not forget that the clinical manifestations of this condition are widely variable and may include multiorganic dysfunction. Although confirmation of diagnosis is based on ADAMTS-13, its associated high mortalitiy requires immediate treatment on mere suspicion.

Thrombocytopenia is a common lab finding. The two fundamental groups are lack of production versus overconsumption of platelets. When common causes of thrombocytopenia have been ruled out and less common causes, such as thrombotic microangiopathic conditions, have been considered, it is important to keep in mind that patients undergoing dialysis may develop thrombocytopenia from the dialyzer itself. This case is of a 51-year-old male who presented originally with celiac artery dissection and acute kidney injury requiring emergent dialysis. He ultimately developed thrombocytopenia during his hospitalization. It was initially presumed to be from thrombocytopenic purpura without improvement after plasmapheresis. No clear etiology was identified until it was suspected that the dialyzer was the source of thrombocytopenia. After changing the dialyzer type, the patient\'s thrombocytopenia resolved. Dialyzer-associated thrombocytopenia is a rare but reversible complication of hemodialysis. It is important to keep this differential in mind for patients undergoing hemodialysis.

UNASSIGNED: Snakebite is a neglected public health issue causing death and disability, disproportionately affecting tropical and subtropical resource poor countries globally. Snakebite-associated thrombotic microangiopathy (TMA) occurs in a subset of snakebites and is associated with acute kidney injury (sometimes requiring renal replacement therapy) and a risk of chronic kidney disease.
UNASSIGNED: This expert review synthesizes current evidence on therapeutic interventions in snakebite-associated TMA via PubMed search for cohort studies and randomized controlled trials (RCTs) in snakebite-associated TMA from 1970 to October 2022.
UNASSIGNED: There are no interventional RCTs in snakebite-associated TMA. Recent cohort studies from Sri Lanka, India, and Australia report clinical and laboratory endpoint outcomes for intervention with antivenom and therapeutic plasma-exchange (TPE). TPE is a resource intense and costly treatment using large volumes of blood donor plasma. There is no consistent evidence supporting TPE in snakebite-associated TMA with respect to patient survival, dialysis-free survival, or hospital length of stay. Antivenom is the standard of care for patients with snake envenoming, but there is no specific evidence of benefit in snakebite-associated TMA. Emerging new therapies in snakebite more broadly are untested in snakebite-associated TMA. RCTs are needed to improve the evidence for treatment of snakebite-associated TMA.

Atypical hemolytic uremic syndrome (aHUS) is a group of disorders that affect kidneys which is rare type of HUS that differs from classical hemolytic uremic syndrome (HUS) by absence of prodromal phase consisting of episodes of diarrhoea due to preceding shiga toxin E. coli (STEC-HUS) infection and is 5% of all HUS cases. Approximately 50% cases present with clinical triad of hemolytic anemia, thrombocytopenia and renal insufficiency. However, it can have unusual clinical features in form of central nervous system involvement. This case, of a 15-year-old Indian boy, is one such rare presentation of atypical haemolytic uremic syndrome associated with posterior reversible encephalopathy syndrome (PRES), or reversible posterior leukoencephalopathy syndrome (RPLS) who presented with anaemia, anasarca, papilledema, hypertension, episodic seizures and significant magnetic resonance imaging (MRI) brain findings. We report this uncommon combination of two syndromes to provide useful insight for clinicians to approach and diagnose such presentation in paediatric patients.

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy (TMA) caused by decreased activity of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13). Platelet-rich thrombi in small vessels lead to fragmentation of RBCs causing microangiopathic hemolytic anemia (MAHA). Therapeutic plasma exchange is life-saving and is the mainstay of the treatment of TTP. Higher dose IV steroids along with rituximab are used as an adjunct to plasma exchange. Our case report describes a 26-year-old healthy male who presented with new onset seizures and encephalopathy. Blood work demonstrated anemia, severe thrombocytopenia, elevated lactate dehydrogenase, decreased haptoglobin, and elevated creatinine, and peripheral blood smear showed marked schistocytosis indicating MAHA. Plasma exchange and high-dose steroids were started on a presumptive diagnosis of TTP. ADAMTS13 activity was undetectable and ADAMTS13 inhibitor levels were elevated. Rituximab and caplacizumab were then added. Symptoms of encephalopathy improved by day five and platelet counts started improving by day nine. After several days of plasma exchange, he showed a \"clinical response\" with several weeks of active treatment. The association between coronavirus disease 2019 (COVID-19) infection and the severity of TTP with multiorgan failure is not well understood yet. Although we describe a successful multimodal approach to the management of TTP, which we believe is secondary to COVID-19 infection, further research is warranted to analyze and understand the pathophysiology by which COVID-19 infection causes TTP. It would help in establishing standardized therapy in the future.