Objective: To report the clinical manifestations and laboratory features of five patients with congenital thrombotic thrombocytopenic purpura (cTTP) and explore its standardized clinical diagnosis and treatment along with a review of literature. Methods: Clinical data of patients, such as age of onset, disease manifestation, personal history, family history, and misdiagnosed disease, were collected. Treatment outcomes, therapeutic effects of plasma infusion, and organ function evaluation were observed. The relationship among the clinical manifestations, treatment outcomes, and ADAMTS13 gene mutation of patients with cTTP was analyzed. Additionally, detection of ADAMTS13 activity and analysis of ADAMTS13 gene mutation were explored. Results: The age of onset of cTTP was either in childhood or adulthood except in one case, which was at the age of 1. The primary manifestations were obvious thrombocytopenia, anemia, and different degrees of nervous system involvement. Most of the patients were initially suspected of having immune thrombocytopenia. Acute cTTP was induced by pregnancy and infection in two and one case, respectively. ADAMTS13 gene mutation was detected in all cases, and there was an inherent relationship between the mutation site, clinical manifestations, and degree of organ injury. Therapeutic or prophylactic plasma transfusion was effective for treating cTTP. Conclusions: The clinical manifestations of cTTP vary among individuals, resulting in frequent misdiagnosis that delays treatment. ADAMTS13 activity detection in plasma and ADAMTS13 gene mutation analysis are important bases to diagnose cTTP. Prophylactic plasma transfusion is vital to prevent the onset of the disease.
Female ; Pregnancy ; Humans ; Adult ; Blood Component Transfusion ; Plasma ; Purpura, Thrombotic Thrombocytopenic/therapy* ; Mutation ; Purpura, Thrombocytopenic, Idiopathic ; ADAMTS13 Protein/therapeutic use*

Humans ; Child ; Purpura, Thrombotic Thrombocytopenic/therapy* ; Consensus

Thrombotic microangiopathy (TMA) is a group of highly heterogeneous, acute and severe clinicopathological syndromes, characterized by microangiopathic hemolytic anemia (MAHA), thrombocytopenia and ischemic injury of end organs. TMA has the characteristics of dangerous condition, multiple organ involvement and high mortality. Patients with severe TMA need to be admitted to intensive care unit (ICU) for organ function support therapy. Early and rapid evaluation, differential diagnosis, and timely and effective treatment are the key to improve the prognosis of TMA patients. Here, we review the pathophysiological changes, diagnosis differential diagnosis, and treatment of the severe TMA in adult.
Adult ; Humans ; Thrombotic Microangiopathies/therapy* ; Purpura, Thrombotic Thrombocytopenic/therapy* ; Anemia, Hemolytic/therapy* ; Treatment Outcome ; Diagnosis, Differential

Objective: To observe the efficacy and adverse reactions of a combination therapy regimen based on bortezomib and glucocorticoids in recurrent/refractory immune thrombocytopenic purpura (iTTP) . Methods: Six patients with recurrent/refractory TTP were included and treated with a glucocorticoid and two courses of bortezomib-based regimen. The clinical remission status of patients, changes in ADAMTS13 activity/ADAMTS13 inhibitor, and the occurrence of treatment-related adverse reactions were observed. Results: Of the 6 patients, 2 were males and 4 were females, with a median age of 21.5 (18-68) years. Refractory TTP was found in 1 case and recurrent TTP in 5 cases. Glucocorticoids were administered with reference to prednisone at 1 mg·kg(-1)·d(-1), and gradually reduced in dosage after achieving clinical remission. Bortezomib is subcutaneously administered at 1.3 mg/m(2) on days 1, 4, 8, and 11 with a 28-day treatment course consisting of 2 courses. Six patients achieved clinical remission after receiving bortezomib as the main treatment. ADMATS13 activity returned to normal in all patients with TTP after treatment, and the ADAMTS13 inhibitor turned negative. Thrombocytopenia is the most common adverse reaction after treatment, with other adverse reactions, including peripheral neuritis and abdominal pain, but ultimately all patients returned to normal. In a median follow-up of 26 (9-41) months, 5 patients maintained sustained remission, and 1 patient relapsed after 16 months of bortezomib treatment. Conclusion: Combination therapy of bortezomib and glucocorticoids has a satisfactory therapeutic effect and controllable adverse reactions for recurrent/refractory iTTP.
Male ; Female ; Humans ; Young Adult ; Adult ; Middle Aged ; Aged ; Bortezomib/therapeutic use* ; Glucocorticoids/therapeutic use* ; Rituximab/therapeutic use* ; Purpura, Thrombotic Thrombocytopenic/drug therapy* ; Purpura, Thrombocytopenic, Idiopathic/drug therapy* ; ADAMTS13 Protein/therapeutic use*

ADAMTS13 Protein ; Asians ; China ; Humans ; Plasma Exchange ; Purpura, Thrombotic Thrombocytopenic/therapy*

INTRODUCTION: ADAMTS13 (a disintegrin-like and metalloproteinase with a thrombospondin Type 1 motif, member 13) plays a fundamental role in the regulation of haemostasis and thrombosis. Its deficiency leads to an accumulation of ultra-large von Willebrand multimers, inducing spontaneous platelet aggregation, thrombosis in the microvasculature, and thrombotic thrombocytopenic purpura (TTP), a condition with 90% mortality when left untreated. Prompt quantification of ADAMTS13 antigen, activity and autoantibody plays a crucial role in the diagnosis and management of TTP and can help differentiate it from other thrombotic microangiopathies (TMAs). Reference ranges for ADAMTS13 are generally derived from Caucasian patients. Given that polymorphism in the ADAMTS13 gene can be associated with variable ADAMTS13 levels, we aimed to establish the first reference range in Singapore and provide a crucial laboratory test for institutions here and elsewhere. METHODS: 150 healthy voluntary donors (75 men, 75 women) aged 21-60 years, with an ethnic mix mirroring Singapore's population profile, were recruited. ADAMTS13 antigen, activity and autoantibody levels were measured using the fluorescence resonance energy transfer-vWF73 and enzyme-linked immunosorbent assay methodologies. RESULTS: Levels (activity 0.65-1.79 IU/mL, antigen 0.36-1.17 IU/mL, autoantibody 1.4-12.5 U/mL) were not statistically different between the genders and various age groups. CONCLUSION TTP and TMAs are encountered in a wide range of specialties. The availability of new assays in Singapore will aid clinicians in the timely management of these conditions. Standardising reference ranges established for Singapore against World Health Organization standards allows harmonisation of measurements between laboratories and for future research collaborations.
ADAMTS13 Protein/analysis* ; Adult ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Male ; Purpura, Thrombotic Thrombocytopenic/diagnosis* ; Reference Values ; Singapore

ADAMTS13 Protein ; Asians ; China ; Humans ; Plasma Exchange ; Purpura, Thrombotic Thrombocytopenic/therapy*

Congenital thrombotic thrombocytopenic purpura, also known as Upshaw-Schulman syndrome, is a rare autosomal recessive genetic disorder. The main pathogenesis is homozygous or compound heterozygous variants of von Willebrand factor lyase (ADAMTS13) gene mapped to chromosome 9q34, which may result in severe lack of ADAMTS13 which cleaves von Willebrand factor (vWF) multimers in the plasma and increase the risk of microvascular thrombosis, leading to various complications. The advance of research on the pathogenesis of cTTP, recombinant human ADAMTS13 and gene therapy have made breakthroughs which may lead to cure of cTTP. This article has provided a review for the latest progress made in the diagnosis and treatment of cTTP.
ADAM Proteins/genetics* ; ADAMTS13 Protein/genetics* ; Homozygote ; Humans ; Purpura, Thrombotic Thrombocytopenic/therapy* ; von Willebrand Factor/genetics*

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy, in which a severe deficiency of von Willebrand factor lyase results in thrombocytopenic clots that block blood vessels and eventually lead to terminal organ failure. Therapeutic plasma exchange is the cornerstone of TTP treatment which can greatly improves the survival rate of the patients. With the further exploration to the pathophysiological mechanism of TTP, other alternative therapies, new immunosuppressive agents, targeted antagonists, gene therapy and other emerging means gradually emerge, which are expected to further reduce the mortality and recurrence rate of the patients. In this review, the new developments in TTP treatment were summarized briefly.
ADAMTS13 Protein ; Humans ; Immunosuppressive Agents ; Plasma Exchange ; Purpura, Thrombotic Thrombocytopenic/therapy* ; von Willebrand Factor

OBJECTIVE: Compared with the method of optical microscopy, to evaluate the accuracy of fragmented red cells(FRC) detection by Sysmex XN-3000. METHODS: A total of 111 samples were collected from patients diagnosed as thrombotic thrombocytopenic purpura, autoimmune disease, hematological disease, malignant tumor and health examination in our hospital from June 2019 to February 2021, including 74 cases in the case group and 37 cases in the healthy control group. All samples were detected by optical microscope and Sysmex XN-3000, respectively. ROC was used to evaluate the detection ability of Sysmex XN-3000 for schistocyte. Bland-Altman method was used to evaluate the consistency of the results of the two methods for detection of schistocyte, and Pearson correlation analysis was conducted for the difference of the results. RESULTS: The area under the ROC curve was 0.890(95% CI: 0.828-0.952, P<0.01). Sysmex XN-3000 count did not quantitatively agree with schistocyte counts by microscopy in the case group(mean of difference:-1.53, 95% limits of agreement: -8.78~5.72). There was a weak positive correlation between platelet count and the difference of analyzer and microscopic results (r=0.32,P<0.05). CONCLUSION Sysmex XN-3000 can be used as a reference for qualitative determination of schistocyte. However, the sensitivity of Sysmex XN-3000 should be improved. It is still necessary to combine with manual microscopy. The quantitative results are not reliable now and cannot be used as a reference for monitoring the results of schistocyte in clinical patients after treatment.
Humans ; Neoplasms ; Platelet Count ; Purpura, Thrombotic Thrombocytopenic ; ROC Curve ; Reproducibility of Results