OBJECTIVES: To investigate the expression of interleukin-37 (IL-37), vascular endothelial growth factor A (VEGFA), and transforming growth factor-β1 (TGF-β1) in children with primary immune thrombocytopenia (ITP) and their correlation with T cells. METHODS: A retrospective analysis was conducted on 45 children with ITP (ITP group) who were admitted to Handan Central Hospital from January 2020 to April 2022, and 30 healthy children who underwent physical examination during the same period were included as the healthy control group. The mRNA expression levels of IL-37, VEGFA, and TGF-β1 and the levels of regulatory T cells (Treg) and helper T cells 17 (Th17) were measured before and after treatment, and the correlation between the mRNA expression levels of IL-37, VEGFA, and TGF-β1 and the levels of Treg, Th17, and Treg/Th17 ratio were analyzed. RESULTS: Compared with the healthy control group, the ITP group had a significantly higher mRNA expression level of IL-37 and a significantly higher level of Th17 before and after treatment, as well as significantly lower mRNA expression levels of VEGFA and TGF-β1 and significantly lower levels of Treg and Treg/Th17 ratio (P<0.05). After treatment, the ITP group had significant reductions in the mRNA expression level of IL-37 and the level of Th17 and significant increases in the mRNA expression levels of VEGFA and TGF-β1 and the levels of Treg and Treg/Th17 ratio (P<0.05). Correlation analysis showed that in the ITP group, the mRNA expression levels of IL-37 and TGF-β1 were negatively correlated with the levels of Treg and Treg/Th17 ratio (P<0.05) and were positively correlated with the level of Th17 (P<0.05) before and after treatment; the mRNA expression level of VEGFA was positively correlated with the levels of Treg and Treg/Th17 ratio (P<0.05) and was negatively correlated with the Th17 level (P<0.05) before and after treatment. CONCLUSIONS Abnormal expression levels of IL-37, VEGFA, and TGF-β1 may be observed in children with ITP, which is significantly associated with the imbalance of Treg/Th17 ratio. It is speculated that the cytokines such as IL-37, VEGFA, and TGF-β1 may be involved in the development and progression of ITP or may become important potential targets for the treatment of children with ITP. Citation:Chinese Journal of Contemporary Pediatrics, 2023, 25(11): 1131-1136.
Child ; Humans ; Interleukins ; Purpura, Thrombocytopenic, Idiopathic ; Retrospective Studies ; RNA, Messenger/metabolism* ; T-Lymphocytes, Regulatory ; Th17 Cells/metabolism* ; Transforming Growth Factor beta1/genetics* ; Vascular Endothelial Growth Factor A/genetics*

Immune checkpoint inhibitors (ICIs) show unique advantages in the treatment of lung cancer, making the treatment of lung cancer enter the era of immunotherapy, but ICIs will also have adverse reactions, and the incidence of immune-induced hematological toxicity is not very high. Immunotherapy-induced thrombocytopenia is a rare adverse event.We report one case of thrombocytopenia induced by ICIs and review the literature on thrombocytopenia associated with ICIs and discuss the clinical features, possible mechanisms, and optimal treatment. 
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Humans ; Purpura, Thrombocytopenic, Idiopathic/drug therapy* ; Lung Neoplasms/drug therapy* ; Thrombocytopenia/chemically induced* ; Antibodies, Monoclonal, Humanized/adverse effects*

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

Humans ; China ; Consensus ; Purpura, Thrombocytopenic, Idiopathic/therapy* ; Thrombocytopenia/therapy* ; Thromboembolism/therapy*

Objective: To determine the efficacy of eltrombopag for primary immune thrombocytopenia (ITP) in adults and the predictive factors for treatment-free response (TFR) . Methods: Clinical data of adults with ITP who received eltrombopag from June 14, 2013 to May 31, 2021 in the Hematology Department of Ruijin Hospital affiliated with Shanghai Jiao Tong University Medical College were retrospectively analyzed. The initial dose of eltrombopag was 25 mg/d, and the maximum dose was 75 mg/d; the dose was adjusted to maintain the platelet count to within 50-150×10(9)/L. Treatment was discontinued according either to the protocol, on the patient's wishes or doctor's judgment (prescription medication), or based on clinical trials. The efficacy of eltrombopag and factors for TFR among patients who achieved complete response and those who discontinued treatment were analyzed. Results: Overall, 106 patients with ITP (33 men and 73 women) were included in the study. The median age of patients was 50 (18-89) years. There were 2, 10, and 94 cases of newly diagnosed, persistent, and chronic ITP, respectively. The complete response rate was 44.3% (47/106), the response rate was 34.0% (36/106), and the overall response rate was 78.3% (83/106). Meanwhile, 83 patients who responded to treatment discontinued eltrombopag; of these, 81 patients were evaluated. Additionally, 17 patients (21.0%) achieved TFR. The median follow-up duration of patients who achieved TFR was 126 (30-170) weeks. The recurrence rate was 17.6% (3/17), and the relapse-free survival rate was 76.5%. The results of univariate analysis revealed that non-recurrence after discontinuation of other treatments for ITP (P=0.001), and platelet count and eltrombopag dose of ≥100×10(9)/L (P=0.007) and ≤25 mg/d (P=0.031), respectively, upon discontinuation of eltrombopag were predictors of TFR; these effects were attributed to prolonged effective duration of eltrombopag. Multivariate analysis showed that there was a correlation between non-recurrence and prolonged effective duration after discontinuation of other treatments for ITP (P=0.002) . Conclusion: Eltrombopag is effective for patients with ITP as it can result in TFR. Predictors for TFR include non-recurrence after discontinuation of concomitant ITP treatment, and platelet count and eltrombopag dose of ≥100 × 10(9)/L and ≤25 mg/d upon discontinuation of treatment, respectively.
Male ; Humans ; Adult ; Female ; Middle Aged ; Aged ; Aged, 80 and over ; Purpura, Thrombocytopenic, Idiopathic/diagnosis* ; Retrospective Studies ; Treatment Outcome ; China/epidemiology* ; Benzoates/therapeutic use*

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*

SARS-CoV-2-induced immune thrombocytopenia (SARS-CoV-2-induced ITP) is an autoimmune disease secondary to virus infections. Its diagnosis is often based on exclusion of other possible causes of thrombocytopenia in COVID-19 patients. Common laboratory examinations include coagulation function, thrombopoietin and drug-dependent antibodies. Since both bleeding and thrombosis risks are seen in SARS-CoV-2-induced ITP patients, individual remedy is essential for the treatment of this disease. Because thrombopoietin receptor agonist(TPO-RA) has the side effect of accelerating thrombosis and may aggravate the pulmonary embolism symptoms of patients, it should be used for refractory SARS-CoV-2-induced ITP patients only. This review briefly summarizes the recent research progress in the pathogenesis, diagnosis and treatment of SARS-CoV-2-induced ITP.
Humans ; Purpura, Thrombocytopenic, Idiopathic/drug therapy* ; SARS-CoV-2 ; COVID-19/complications* ; Thrombocytopenia ; Thrombosis/drug therapy* ; Thrombopoietin/therapeutic use* ; Recombinant Fusion Proteins/therapeutic use*

Immune thrombocytopenia (ITP) is an immune-mediated acquired hemorrhagic autoimmune disease. At present, the first-line therapeutic drugs for ITP include glucocorticoids and intravenous immunoglobulins. However, about 1/3 of the patients had no response to the first-line treatment, or relapsed after dose reduction or withdrawal of glucocorticoids. In recent years, with the gradual deepening of the understanding on the pathogenesis of ITP, the drugs targeting different pathogenesis continually emerge, including immunomodulators, demethylating agents, spleen tyrosine kinase (SYK) inhibitors and neonatal Fc receptor (FcRn) antagonist. However, most of these drugs are in clinical trials. This review summarized briefly the recent advances in the treatment of glucocorticoids resistance and relapsed ITP, so as to provide reference for the clinical treatments.
Infant, Newborn ; Humans ; Purpura, Thrombocytopenic, Idiopathic/drug therapy* ; Glucocorticoids/therapeutic use* ; Thrombocytopenia ; Immunoglobulins, Intravenous/therapeutic use* ; Immunologic Factors/therapeutic use*

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*

Pregnancy ; Female ; Humans ; Purpura, Thrombocytopenic, Idiopathic ; Thrombocytopenia ; Platelet Count