Thrombotic thrombocytopenic purpura (TTP), a group of microvascular thrombohemorrhagic syndromes, is a highly lethal, high-risk clinical emergency, and early diagnosis and initiation of plasma exchange (PEX) effectively improves prognosis and increases survival. The main clinical features include microangiopathic hemolytic anemia, thrombocytopenia, neuropsychiatric symptoms, fever, and renal involvement. The pathogenesis is related to severe deficiency of VWF (vascular hemophilia factor) metalloprotein cleaving enzyme ADAMTS13, abnormal VWF release from vascular endothelial cells, and abnormal platelet activation. It is clinically divided into hereditary TTP (mutations in the ADAMTS 13 gene, resulting in decreased or deficient enzyme activity) and acquired TTP [1]. It should be noted that the diagnosis and treatment of TTP is extremely challenging because 1) the diagnostic criteria are not precise, 2) the survival rate without plasma replacement is only 10%, and 3) although PEX can lead to survival in 80% of patients, they face a high risk of numerous PEX-related complications [2]. There are practical problems in clinical practice such as delayed diagnosis due to insufficient knowledge of the disease; or delayed optimal treatment due to excessive concern about PEX complications; or over-reliance on the detection of ADAMTS13 activity; or over-diagnosis of TTP and over-treatment. In this article, we will discuss our experience in relation to clinical practice and literature. I. Acquired TTP is complex and variable, and differential diagnosis is particularly important. To be precise, TTP is a generic name for microangiopathic hemolysis and thrombocytopenia with or without neurological and renal abnormalities in adults. Acquired TTP is divided into idiopathic TTP (presence of ADAMTS 13 autoantibodies, i.e., detection of ADAMTS 13 inhibitors) and secondary TTP (induced by factors such as infections, drugs, tumors, autoimmune diseases, hematopoietic stem cell transplantation, pregnancy, etc., with poor prognosis). The former treatment is based on PEX and immunosuppression, while the key to the latter is to remove the primary factors as soon as possible. the diagnosis of TTP is the so-called “triad” (microangiopathic hemolytic anemia, thrombocytopenia, neuropsychiatric symptoms), “quintuple” (microangiopathic Hemolytic anemia, thrombocytopenia, neuropsychiatric symptoms, renal loss, and fever) are well known, but it is quite difficult to make a real clinical assessment and management of the disease initially based on them. First, the classic “five signs” are hardly seen in clinical practice, and most patients present only with microangiopathic hemolytic anemia and thrombocytopenia, with neurological and renal abnormalities being uncommon and fever being rare [2]. Second, patients found clinically with evidence of microangiopathic hemolytic anemia and thrombocytopenia generally have no difficulty considering the possibility of the presence of TTP, but in a short period of time to determine whether idiopathic TTP or secondary TTP; to exclude diseases such as hemolytic-uremic syndrome (HUS), diffuse intravascular coagulation (DIC), HELLP syndrome, Evans syndrome, pregnancy, eclampsia The concomitant microangiopathic hemolytic anemia and thrombocytopenia are not easy to treat [3]. Because of this, it triggers difficult treatment decisions. Especially in idiopathic TTP, early diagnosis and timely initiation of critical treatment PEX and immunosuppression are decisive factors for successful salvage. Therefore, once the clinical diagnosis of TTP is clear or highly suspected, regardless of its severity, it should be treated aggressively as soon as possible (including PEX, glucocorticoids, etc.); at the same time, causative factors should be screened as soon as possible and the treatment plan should be revised in a timely manner (e.g., sepsis-related TTP must be treated with a strong anti-infective focus, not PEX or immunosuppressive therapy) [1-3]. Second, the significance of the ADAMTS13 assay was first demonstrated in 1997 for chronic recurrent TTP associated with the presence of abnormally large VWF multimers in plasma, followed soon after by the discovery that patients with TTP have a severe defect in the major regulator of VWF size, ADAMTS13, which is important in the prevention of spontaneous microvascular platelet aggregation and is a major pathophysiological product [4]. We know that acquired ADAMTS13 deficiency is often due to increased anti-ADAMTS13 autoantibody activity or ADAMTS13 clearance in circulating blood. assay of ADAMTS13 activity was therefore once used as an important indicator for TTP diagnosis and therapeutic evaluation. After more than 10 years of observational clinical studies, most scholars have concluded that ADAMTS13 activity measurement may not be useful for initial treatment decisions; although severe ADAMTS13 deficiency (<10%< span="">) is one of the features of TTP, it is neither sufficiently sensitive nor specific for the decision to initiate or withdraw PEX [2].George JN et al. showed that not all patients with severe ADAMTS13 deficiency can be identified with TTP [2,3]. In a group of 65 patients with severe ADAMTS13 deficiency, six cases were found to have other diseases after starting PEX, five of which had systemic infections (including hematopoietic stem cell transplant patients) and one case was diagnosed as Kaposi’s sarcoma after autopsy [5]. Patients with TTP with severe ADAMTS13 deficiency are at risk of relapse, especially within 1 year of remission most commonly, with an expected 7.5-year risk of relapse of 41%, whereas relapse is rare in patients without severe ADAMTS13 deficiency. Therefore, the possibility of future relapse can be inferred clinically based on the severity of ADAMTS13 deficiency at the time of the patient’s initial episode, with a view to enhancing monitoring of platelet counts, timely detection of the first signs of relapse, early intervention, and reduction of TTP-related complications. clinical data related to the value of ADAMTS13 activity assay in predicting relapse after TTP remission suggest that many patients have persistent or intermittent ADAMTS13 deficiency after recovery. ADAMTS13 deficiency. 41 patients with severe ADAMTS13 deficiency underwent ADAMTS13 activity assays 1 to 4 times during remission, which revealed ADAMTS13 activity <10%< span=""> in 7 (17%), <50%< span=""> in 19 (46%), and the presence of ADAMTS13 inhibitors in 9 (22%). substance. This indicates that severe ADAMTS13 deficiency in remission is not associated with clinical symptoms of TTP, and its clinical importance and risk of relapse are not certain. It is not considered necessary to routinely test for ADAMTS13 activity after recovery from TTP [3]. In conclusion, knowledge of the role of ADAMTS13 contributes to the understanding of the pathogenesis of TTP, while initial assessment and disposition decisions remain largely dependent on clinical judgment. Third, the importance of comprehensive treatment of TTP is emphasized TTP has an acute onset and rapid progression and is tricky to treat. The key lies in weighing whether the possibility of TTP diagnosis is sufficient to avoid the risk of PEX treatment. Some data suggest that high titers of anti-ADAMTS13 antibodies are a high risk factor for complications and mortality associated with TTP treatment. Clinical decisions about the treatment of PEX must sometimes be made before it is too late to find the etiology of TTP, such as the possibility of neurological abnormalities, renal failure, or death if there is a slight delay in the diagnosis of suspected drug-associated TTP, and treatment strategies can be adjusted after the etiology is clarified. Clinical practice in recent years has found that PEX therapy is equally effective in patients without severe ADAMTS13 deficiency, suggesting that PEX can replace ADAMTS13-deficient plasma and that the assumption of autoantibody clearance does not apply to all patients. Plasma transfusions can be of transient benefit before starting PEX, gaining time for further treatment. After starting PEX therapy, the next step is to decide whether to activate glucocorticoids and to adjust the dose of hormone use according to the severity of the patient’s disease. The goal is to suppress autoantibodies against ADAMTS13 activity and to enhance the efficacy of PEX, with a significant benefit in patients with severe ADAMTS13 deficiency. If the patient is unlikely to have ADAMTS13 deficiency, such as severe acute renal failure, or if there is a history and clinical features of drug-related TTP or TTP associated with E. coli infection, hormone therapy is not advocated. Idiopathic TTP with persistent positive ADAMTS13 inhibitors after hormone therapy may be treated with additional immunosuppressive agents such as vincristine, cyclophosphamide, and cyclosporine with a view to reducing autoantibody production and controlling disease progression. Intravenous gammaglobulin can be used in patients with ineffective PEX or multiple recurrences [1-3]. For relapsed refractory idiopathic TTP, anti-CD20 monoclonal antibodies (rituximab, melphalan) can also be added, and melphalan 375 mg/m2/week x 4 weeks is recommended. Recent studies have reported that rituximab may also be used as a routine initial treatment, but there are still problems with patient selection and analysis, such as unblinding, poorly matched control group treatment, variable follow-up time in each group, lack of RFS (relapse-free survival) information, and not all patients have severe ADAMTS13 deficiency, which makes it unconvincing [5]. Furthermore, the available data suggest that treatment with PEX and glucocorticoids alone led to timely remission in many patients with severe ADAMTS13 deficiency, and most of them did not relapse, thus also not indicating the value of rituximab application. Regarding the risks of platelet transfusion in patients with TTP, the biology is obvious and should be used with clinical caution. The side effects of platelet transfusion have also been reported to be insignificant: 33/54 (61%) patients with severe ADAMTS13 deficiency received one or more platelet transfusions (mostly before consideration or establishment of a TTP diagnosis) and found no difference in mortality and incidence of severe neurological events between those who received or did not receive platelet transfusions. Therefore, it is considered that platelet transfusion is equally appropriate in patients with TTP who have severe thrombocytopenia and significant bleeding or require invasive therapeutic measures, but central venous catheter implantation is not necessary for platelet transfusion [2]. That is, for patients with TTP, severe thrombocytopenia is not in itself an indication for platelet transfusion, but no additional side effects have been observed with platelet transfusion in the prevention or management of bleeding associated with TTP. Fourth, timely detection of relapse and control is the key to successful TTP treatment TTP relapse is defined as the recurrence of clinical manifestations of TTP 30 days after the first episode of complete remission, with an incidence of about 30-40%, mostly within 1 year after the first episode of the disease. Idiopathic TTP with hereditary TTP and ADAMTS13 inhibitor positivity is prone to recurrence. Regular follow-up monitoring of platelet counts is extremely important and is the main indicator of TTP treatment and relapse; ADAMTS 13 activity testing in patients with first-episode TTP can help determine prognosis; relapse should be noted in those with persistent positive ADAMTS 13 inhibitors. Most experts do not currently advocate maintenance therapy for the prevention of TTP recurrence. It has been suggested that the addition of melphalan during acute exacerbations is expected to reduce disease recurrence [2,6]. In general, the survival of TTP relapse treatment is better than that of first-episode patients due to enhanced monitoring, early recognition of relapse and timely treatment. In summary, the classic clinical pentad manifestations of TTP are rarely seen, and many patients have only thrombocytopenia and microangiopathic hemolytic anemia, making the diagnosis of the first episode difficult; PEX is the first choice for the treatment of TTP, while attention should be paid to the search for possible causative factors, and once the primary factor is identified, treatment of the primary disease should be the main focus; adjuvant glucocorticoid therapy and selective application of rituximab may reduce the Adjuvant glucocorticoid therapy and selective application of rituximab can reduce the time required to obtain disease remission and the number of PEXs, thus avoiding complications associated with PEX treatment; meticulous follow-up after recovery from TTP is extremely important.