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1.
J Surg Res ; 245: 643-648, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31536907

RESUMO

BACKGROUND: As medical therapy improves, splenectomy has been relegated to third- or fourth-line therapy for immune thrombocytopenic purpura (ITP) in many hematologic practices. However, these medications have well-known associated morbidity and changes in treatment algorithms may affect the timing and degree of response to splenectomy as well as complications in heavily treated ITP patients. MATERIALS AND METHODS: This is a retrospective study of consecutive patients who underwent ITP splenectomy from January 1994 to June 2017. Nonresponders after splenectomy and those with recurrent disease were compared to complete responders. RESULTS: The cohort included 84 patients. Median number of medications received before splenectomy was 3 (1-6). 14.3% of patients had a medication-related complication, including heart failure, adrenal insufficiency, diabetes mellitus, infection, and osteoporosis. After splenectomy, 83.5% had a complete response, 7.5% partial response, and 9% no response. Complete response was associated with response to steroids before surgery (P < 0.01). Among responders, 19% had recurrent disease, which was associated with lower platelet count at diagnosis (P < 0.01). Forty-four patients (52.0%) had nonelective splenectomies for persistent bleeding or dangerously low platelets despite maximal medical therapy. Ten patients had Clavien-Dindo grade II or higher surgical complications (11.9%). Seven of these complications were related to recurrent or refractory ITP. CONCLUSIONS: Many ITP patients have complications related to medication use, and 52.0% required nonelective splenectomy despite maximal medical therapy. Earlier splenectomy may avoid medication-related complications and may reduce the complications from splenectomy. Splenectomy remains an effective and safe treatment for ITP.


Assuntos
Púrpura Trombocitopênica Idiopática/cirurgia , Esplenectomia/métodos , Corticosteroides/uso terapêutico , Adulto , Idoso , Feminino , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Estudos Retrospectivos , Esplenectomia/efeitos adversos
2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1602-1606, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31607319

RESUMO

OBJECTIVE: To investigatc the curative efficacy of low dose rituximab for glucocorticoid ineffective on dependent ITP patients and its relation with sensitivity to glucocorticoid so as to provide reference basis for rational use of drugs in clinical treatmant. METHODS: Seventy-ninth ITP patients enrolled in this study included the glucocorticoid-ineffective patients (19 cases) and glucocorticoid-dependent patients (60 cases). All ITP patients were treated with regimen consisted of high dose dexamethasone plus low dose rituximab (dexal-methasone 40 mg/d for 4 days per os, ritaximab 100 mg by intravenous infusion at D7, 14, 21 and 28 respectively). The patients after treatment were followed-up for 12 month, and the relation of patients sensitivity to glucocorticoid with therapentic response of rituximab was analyzed. The changes of Treg cell ratio and BAFF, IL-2 and sCD40L levels before and after treatment were detected by flow cytometry and ELISA respectively. RESULTS: The overall response rate (ORR) of patients treated with above- mentioned regemen at 1, 3, 6 and 12 months after treatment was 79.7% (63/79), 69.6% (55/79), 63.3% (50/79) and 60.8% (48/79) respectivcly, out of which the ORR of glucocorticoid ineffective and glucocorticoid-dependent ITP patients treated with above-mentioned regimen at 1, 3, 6 and 12 months after treatment was 47.4% (9/19) vs 90.0% (54/60), 36.8% (7/19) vs 80.0% (48/60), 21.1% (4/19) vs 76.7% (46/60), 21.1% (4/19) vs 73.3% (44/60), and the difference between 2 groups was statistically significant. The detection of T reg cell showed that the T reg cell ratio in glucocorticoid- ineffective and dependent patients at 1, 3, 6 and 12 months after treatment was (1.70±0.43)% vs (3.47±0.72)%, (1.66±0.33)% vs (4.29±0.91)%, (1.71±0.37)% vs (4.44±0.97)%, (3.36±0.54)% vs (4.29±1.04)%, respectively. The detection of cytokines showed that the levels of BAFF, IL-2 and sCD40L in plasma of glucocorticoid-dependent patients at 1 month after treatment significanlly decreased (P<0.05), the levels of BAFF, IL-2 and sCD40L in plasma of glucocorticoid-ineffective patients although decreased at 1 mouth after treatment, but there was no statistical difference as compared with glucocosticoid-depenment patients. CONCLUSION: The treatment of glucocorticoid-dependent ITP patients with rituximab is more effective. The regulatory effect of rituximab on the T-reg cells, BAFF, IL-2 and sCD40L may be one of its mechanisms.


Assuntos
Púrpura Trombocitopênica Idiopática , Rituximab/uso terapêutico , Dexametasona , Glucocorticoides , Humanos , Inosina Trifosfato , Púrpura Trombocitopênica Idiopática/tratamento farmacológico
3.
Ann Hematol ; 98(11): 2497-2506, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31595308

RESUMO

Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by a low platelet count and consequent increased risk of bleeding. The etiology underlying this condition remains poorly understood. The aim of this study is to evaluate the association of a single nucleotide polymorphism (SNP) rs4077515 in the caspase recruitment domain-containing protein 9 (CARD9) gene with the pathogenesis and therapy of ITP. Two hundred ninety-four patients with ITP and 324 age-matched healthy participants were recruited in this case-control study. Genotyping of CARD9 rs4077515 polymorphism was performed by Sanger sequencing. Our results revealed that a polymorphism rs4077515 in CARD9 gene is associated with decreased risk of susceptibility to and severity of ITP (susceptibility: codominant, AA vs. GG, OR = 0.175, 95% CI = 0.054-0.776, p = 0.001; recessive, GG + AG vs. AA, OR = 6.183, 95% CI = 2.287-16.715, p < 0.001; severity: allele, A vs. G, OR = 0.685, 95% CI = 0.476-0.985, p = 0.041; codominant, AG vs. GG, OR = 0.571, 95% CI = 0.350-0.931, p = 0.025; dominant, AA + AG vs. GG, OR = 0.558, 95% CI = 0.343-0.907, p = 0.019). The existence of the allele A, the mutant AA genotype and the heterozygous AG genotype of CARD9 rs4077515, plays a protective role in ITP. However, CARD9 rs4077515 polymorphism had no effect on corticosteroid sensitivity or refractoriness of ITP.


Assuntos
Proteínas Adaptadoras de Sinalização CARD/genética , Polimorfismo de Nucleotídeo Único , Púrpura Trombocitopênica Idiopática/genética , Corticosteroides/uso terapêutico , Adulto , Alelos , Proteínas Adaptadoras de Sinalização CARD/fisiologia , Estudos de Casos e Controles , Resistência a Medicamentos , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Risco
5.
BMJ Case Rep ; 12(9)2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31540926

RESUMO

A boy developed immune thrombocytopenia 2 weeks after receiving his measles-mumps-rubella and varicella vaccines at 12 months of age. He then had a recurrent episode 1 week after the booster doses of his quadrivalent diphtheria-tetanus-pertussis-polio, pneumococcal and meningococcal group C vaccines at 5 years of age. On both the occasions he required hospitalisation and treatment with intravenous immunoglobulin. He received other vaccines, before and in between, without any adverse events. Future vaccines are to be determined on an individual risk-benefit basis and he will be reviewed at the age of 11 when his next routine immunisations are due.


Assuntos
Vacina contra Difteria, Tétano e Coqueluche/efeitos adversos , Imunização Secundária/efeitos adversos , Imunoglobulinas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Vacina contra Sarampo-Caxumba-Rubéola/efeitos adversos , Vacina Antipólio de Vírus Inativado/efeitos adversos , Púrpura Trombocitopênica Idiopática/induzido quimicamente , Anticorpos Antibacterianos , Criança , Vacina contra Difteria, Tétano e Coqueluche/imunologia , Humanos , Esquemas de Imunização , Masculino , Vacina contra Sarampo-Caxumba-Rubéola/imunologia , Vacina Antipólio de Vírus Inativado/imunologia , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/fisiopatologia , Recidiva , Resultado do Tratamento , Vacinas Combinadas/efeitos adversos , Vacinas Combinadas/imunologia
6.
Blood Coagul Fibrinolysis ; 30(7): 350-356, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31433305

RESUMO

: Asymptomatic patients with primary chronic immune thrombocytopenia (ITP) are not recommended treatment if their platelet counts are above 30 × 10/l. Factors such as age and comorbidities may influence clinical manifestations and should be considered for treatment decisions. The aim of this study was to determine the impact of clinical characteristics for initiation of ITP treatment, and the patterns of ITP treatment given. We performed an observational cohort study in Sweden with information from medical records and National Health Registers. Adults diagnosed with incident primary ITP between years 2009 and 2016 were included. Multinomial logistic regression was used to assess the impact of factors predicting treatment start. Out of 858 patients with chronic ITP from 71 hospitals we identified 585 (68%) with a first ITP treatment. For 537 (92%) corticosteroids were the first choice. The median platelet counts at start of treatment was 12 × 10/l (interquartile range 5-27 × 10/l). The variables predicting treatment start were platelet counts below 20 × 10/l and treatment with antihypertensive drugs. Patients with diabetes were less likely to receive corticosteroids. Severe bleeding occurred in 75 (13%) of the patients. Platelet counts below 20 × 10/l, antihypertensive treatment and bleedings were the strongest predictors of treatment start, diabetes yielded lower odds to start corticosteroid treatment. The majority of the patients had corticosteroids as first treatment while second treatment was diverse. Asymptomatic thrombocytopenia is not considered a reason as such for initiating treatment. In the latter years, splenectomy seemed to occur later in the course of treatment.


Assuntos
Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/epidemiologia , Corticosteroides/uso terapêutico , Adulto , Estudos de Coortes , Feminino , Hemorragia/etiologia , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Púrpura Trombocitopênica Idiopática/terapia , Esplenectomia , Suécia
7.
Int J Immunopathol Pharmacol ; 33: 2058738419872120, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31438744

RESUMO

The treatment of severe chronic immune thrombocytopenia (SCITP) in pediatric patients is challenging. We evaluated the clinical efficacy and safety of eltrombopag in children with SCITP in China. This observational study was carried out at the Hematology Oncology Center, Beijing Children's Hospital between April 2017 and July 2018. Patients with SCITP who had at least 12 weeks of eltrombopag treatment and follow-up data were included. Baseline data, such as age, drug dosage, pre-study platelet count, concomitant medications, and bleeding severity, were collected. Treatment response rates, durable response rates, bleeding events, and adverse events were assessed during eltrombopag therapy for at least 12 weeks. The median duration of eltrombopag therapy was 16 (12-48) weeks. The overall, complete, and partial response rates were 75% (15/20), 35% (7/20), and 40% (8/20), respectively. The durable response rate was 70% (14/20). No serious bleeding events or serious adverse events occurred during the study period. Eltrombopag appears to be effective and safe in children with SCITP, although additional research is needed to confirm this.


Assuntos
Benzoatos/efeitos adversos , Benzoatos/uso terapêutico , Doença Crônica/tratamento farmacológico , Hidrazinas/efeitos adversos , Hidrazinas/uso terapêutico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Adolescente , Criança , Pré-Escolar , China , Feminino , Humanos , Lactente , Masculino , Contagem de Plaquetas/métodos , Resultado do Tratamento
8.
Thromb Res ; 181: 10-16, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31323447

RESUMO

BACKGROUND: Primary immune thrombocytopenia (ITP) is an autoimmune heterogeneous disorder of which Treg cells are numerically or functionally deficient. It is known that human FoxP3+CD4+ T cells were composed of 3 phenotypically and functionally distinct subpopulations (resting Treg, rTreg; activated Treg, aTreg; and non-suppressive Treg, n-sTreg). The current study was aimed to determine whether these Treg subtypes are altered in ITP patients and the related potential clinical applications. METHOD: Normal control volunteers and newly diagnosed ITP patients were enrolled in the study. The percentage of Treg cells' subtypes in peripheral blood was examined by flow cytometry before and after the glucocorticoid treatment. The IL-10 production by Treg subtypes was also examined. RESULTS: Treg cell subtypes of aTreg increased, rTreg decreased, and n-s Treg increased in newly diagnosed ITP patients' peripheral blood. The IL-10 production by respective Treg subtype didn't change after the treatment, and aTreg cells had the highest IL-10 yield. Patients who gained remission during follow-up had a higher aTreg cells' percentage than those who did not at the disease diagnosis. CONCLUSION: Tregs cell subtypes percentage was altered when ITP occurred. The increased aTreg cells at disease diagnosis might predict a better glucocorticoid treatment efficacy.


Assuntos
Glucocorticoides/uso terapêutico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Linfócitos T Reguladores/imunologia , Adolescente , Adulto , Idoso , Feminino , Glucocorticoides/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Adulto Jovem
9.
Chin J Integr Med ; 25(7): 483-489, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31278626

RESUMO

Chronic primary immune thrombocytopenia (CITP) is the most common acquired autoimmune disease that seriously threaten the physical and mental health of patients. Compared with Western medicine treatment, the intervention and treatment of Chinese medicine (CM) has shown certain therapeutic advantages. This paper reviewed the new pathogenesis progress on T cell immune abnormality in CITP, and CM studies on interferes effects of cellular immune regulation of CITP in recent years. Qi deficiency failing to control blood and internal obstruction of blood stasis are the two common types of CM syndromes in CITP patients, the corresponding treatments include invigorating Pi (Spleen), supplementing qi, activating blood, as well as tonifying qi and activating yang, regulating Gan (Liver) to invigorate Pi. The authors also mentioned the problems in the research field of CM for CTIP treatment, and put forward new ideas for the research in the future.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Imunidade Celular , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/imunologia , Pesquisa , Hemorragia/tratamento farmacológico , Humanos
10.
Acta Dermatovenerol Croat ; 27(2): 121-123, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31351508

RESUMO

Psoriasis has been linked to several comorbidities, including metabolic syndrome, atopy, and celiac disease. However, the association between immune thrombocytopenia and psoriasis has rarely been described. We report the case of an adolescent with severe psoriasis and concomitant immune thrombocytopenia who obtained remission during treatment with adalimumab. Increased concentration of tumor necrosis factor-α seems to be a pathogenic linkage and therapeutic target for both diseases.


Assuntos
Adalimumab/uso terapêutico , Psoríase/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Adolescente , Feminino , Humanos , Qualidade de Vida , Indução de Remissão
11.
Drugs ; 79(12): 1305-1319, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31292909

RESUMO

Eltrombopag is an orally available thrombopoietin receptor agonist indicated for the treatment of immune thrombocytopenia (ITP). Beyond the effect on megakaryopoiesis, the drug also showed a stimulating effect on the hematopoietic stem cell with consistent clinical efficacy in aplastic anemia (AA) and myelodysplastic syndromes (MDS). Eltrombopag is highly effective in ITP and less so in AA and MDS. This observation underlines the importance of residual normal hematopoiesis, which is maximal in ITP, minimal/absent in AA, and dysregulated in MDS. In ITP, the drug at 50-75 mg daily induced up to 85% responses both in clinical trials and real-life studies, with the possibility of tapering and discontinuation. In AA, eltrombopag at 150 mg daily was effective in about 40% of cases relapsed/refractory to standard immunosuppression or ineligible for bone marrow transplant. In MDS, the drug seems less effective, with responses in about a quarter of patients at various schedules. The efficacy of eltrombopag in ITP, AA, and MDS suggests the existence of common immune-pathological mechanisms in these diseases, including autoimmunity against peripheral blood cells and bone marrow precursors, as well as a possible evolution of one condition into the other. Additional mechanisms of action emerging from the clinical use of eltrombopag include modulation of T-regulatory cells, restoration of Fc-γ receptor balance in phagocytes, and an iron-mobilizing effect. In this review, we analyzed the most recent literature on eltrombopag use and efficacy in patients with ITP, AA, and MDS, exploring the basis for different dosing, combined treatments, and discontinuation in each context.


Assuntos
Anemia Aplástica/tratamento farmacológico , Benzoatos/uso terapêutico , Hidrazinas/uso terapêutico , Megacariócitos/imunologia , Síndromes Mielodisplásicas/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Pirazóis/uso terapêutico , Benzoatos/administração & dosagem , Benzoatos/efeitos adversos , Humanos , Hidrazinas/administração & dosagem , Hidrazinas/efeitos adversos , Imunomodulação , Imunossupressão , Púrpura Trombocitopênica Idiopática/imunologia , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Receptores de Trombopoetina/agonistas
12.
Blood Coagul Fibrinolysis ; 30(6): 295-299, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31259778

RESUMO

: Thrombopoietin receptor agonists (TPO-RA) are currently approved to treat chronic immune thrombocytopenia (ITP) but there is increasing interest in considering these drugs earlier during the course of the disease. We present six patients with primary ITP resistant to corticosteroids and intravenous immunoglobulins, who received TPO-RA in the persistent phase and then underwent splenectomy in the chronic phase. Eltrombopag was administered as a second-line therapy in four patients, whereas two patients received romiplostim. Five out of six patients rapidly reached response or complete response (four and one, respectively) and steroid suspension. In one case, remission was obtained with steroid and TPO-RA. No significant side effects were reported. After splenectomy, complete response and response was reached in four and two patients, respectively. One relapse was recorded, rescued by steroid and eltrombopag. Postsplenectomy complication was registered in one patient (grade 4 intra-abdominal bleeding). TPO-RA could be a valuable choice in ITP patients in persistent phase candidates to splenectomy.


Assuntos
Benzoatos/uso terapêutico , Hidrazinas/uso terapêutico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Pirazóis/uso terapêutico , Receptores Fc/uso terapêutico , Receptores de Trombopoetina/agonistas , Proteínas Recombinantes de Fusão/uso terapêutico , Trombopoetina/uso terapêutico , Corticosteroides/farmacologia , Doença Crônica , Resistência a Medicamentos , Feminino , Humanos , Imunoglobulinas Intravenosas/farmacologia , Masculino , Púrpura Trombocitopênica Idiopática/cirurgia , Esplenectomia
13.
Rinsho Ketsueki ; 60(5): 480-487, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31168017

RESUMO

Although immune thrombocytopenia (ITP) and thrombotic thrombocytopenic purpura (TTP) appear similar, their symptoms differ. The number of domestic patients diagnosed with ITP and TTP annually has been estimated to be around 24,000 and 400, respectively. Moreover, no major differences in the incidence rate, age of onset, and prognosis have been observed between Europe, the United States (US), and Japan. Both ITP and acquired TTP are autoimmune diseases that require immunosuppressive therapy, though lethal TTP requires the use of plasma exchange in combination with immunosuppression. In Europe and the US, the monoclonal antibody rituximab has been widely used for ITP and TTP since approximately 10 years ago. However, no public health insurance indication has been available for rituximab in Japan. For this reason, investigator-initiated clinical trials were conducted. As a result, rituximab had subsequently been indicated for ITP in 2017. Meanwhile, TTP was designated as an intractable disease in Japan in 2015, and the first clinical practice guidelines were published in 2017. A single-arm study involving rituximab was conducted on high-risk patients in whom treatment with five plasma exchanges was ineffective or ADAMTS13 inhibitor was >2 BU/ml. Approval for the new indication of rituximab for acquired TTP is expected in 2019.


Assuntos
Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Rituximab/uso terapêutico , Proteína ADAMTS13/antagonistas & inibidores , Ensaios Clínicos como Assunto , Humanos , Japão , Troca Plasmática
14.
Ann Hematol ; 98(8): 1845-1854, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31154474

RESUMO

Primary immune thrombocytopenia is an autoimmune disease, characterized with decreased platelet and increased risk of bleeding. Recent studies have shown the reduction and dysfunction of regulatory T (Treg) cells in ITP patients. CD39 is highly expressed on the surface of Treg cells. It degrades ATP to AMP and CD73 dephosphorylates AMP into adenosine. Then adenosine binds with adenosine receptor and suppresses immune response by activating Treg cells and inhibiting the release of inflammatory cytokines from effector T (Teff) cells. Adenosine receptor has several subtypes and adenosine A2A receptor (A2AR) plays a crucial role especially within lymphocytes. The CD39+ Treg cells and the expression of A2AR showed abnormality in some autoimmune disease. But knowledge of CD39+ Treg cells and A2AR which are crucial in the adenosine immunosuppressive pathway is still limited in ITP. Thirty-one adult patients with newly diagnosed ITP were enrolled in this study. CD39 and A2AR expression was measured by flow cytometry and RT-PCR. The function of CD39 was reflected by the change of ATP concentration detected by CellTiter-Glo Luminescent Cell Viability Assay. CD39 expression within CD4+CD25+ Treg cells in ITP patients was decreased compared to normal controls. After high-dose dexamethasone therapy, response (R) group showed increased CD39 expression within Treg cells while non-response (NR) group did not show any difference in contrast to those before treatment. The expression of A2AR in CD4+CD25- Teff and CD4+CD25+ Treg cells was both lower in ITP patients than that of normal controls. After therapy, CD4+CD25- Teff cells had higher A2AR expression while CD4+CD25+ Treg cells did not show any difference in comparison to that before treatment. The enzymatic activity of CD39 was damaged in ITP patients and improved after high-dose dexamethasone therapy. In ITP, there was not only numerical decrease but also impaired enzymatic activity in CD39+ Treg cells. After high-dose dexamethasone treatment, these two defects could be reversed. Our results also suggested that ITP patients had reduced A2AR expression in both CD4+CD25+ Treg cells and CD4+CD25- Teff cells. CD4+CD25- Teff cells had increased A2AR expression after treatment.


Assuntos
Apirase/genética , Dexametasona/uso terapêutico , Imunossupressores/uso terapêutico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Receptor A2A de Adenosina/genética , Linfócitos T Reguladores/efeitos dos fármacos , Adenosina/imunologia , Adenosina/metabolismo , Trifosfato de Adenosina/imunologia , Trifosfato de Adenosina/metabolismo , Adulto , Idoso , Apirase/imunologia , Estudos de Casos e Controles , Feminino , Expressão Gênica , Humanos , Imunofenotipagem , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/enzimologia , Púrpura Trombocitopênica Idiopática/genética , Púrpura Trombocitopênica Idiopática/imunologia , Receptor A2A de Adenosina/imunologia , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/enzimologia , Linfócitos T Citotóxicos/imunologia , Linfócitos T Reguladores/enzimologia , Linfócitos T Reguladores/imunologia
15.
Transfus Apher Sci ; 58(4): 491-494, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31105060

RESUMO

OBJECTIVES: Assess the appropriateness of the use of intravenous immunoglobulin (IVIG) for immune thrombocytopenia (ITP). BACKGROUND: IVIG is suggested for ITP when a rapid increase in platelet count is desired or as first line therapy if corticosteroids are contraindicated. A recent Canadian audit of IVIG requests found a lack of compliance with provincial requirements and inadequate documentation of efficacy which led the authors to conclude that the use of IVIG was broadly inappropriate for all treated diseases. METHODS: Retrospective review of patients with ITP who received IVIG at our institution over a one-year period. RESULTS: 40 patients received IVIG for ITP over the study period for a total of 76 infusions. The most common indications for IVIG within currently accepted guidelines were: active bleeding (13, 17%), pre-operative or antepartum care (22, 29%), contraindication to corticosteroids (8, 11%), and requirement for antithrombotic or myelosuppressive therapy (5, 7%). Indications that fell outside of guidelines included use of IVIG as a diagnostic challenge where the etiology of thrombocytopenia was unclear. IVIG was generally well tolerated. CONCLUSION: At our institution, use of IVIG for ITP was generally appropriate and carefully considered. Detailed utilization/knowledge data inquiries are required to develop tools and policies to enhance appropriate IVIG use in multiple settings.


Assuntos
Imunoglobulinas Intravenosas/administração & dosagem , Auditoria Médica , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Administração Intravenosa , Adulto , Canadá/epidemiologia , Feminino , Humanos , Masculino , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/epidemiologia , Estudos Retrospectivos
16.
Int Immunopharmacol ; 73: 181-192, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31102993

RESUMO

BACKGROUND: Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by the restrained production of new platelets and the persistent reduction of existing platelets. An imbalance between Th17 and Treg cells is associated with a decrease in platelets. However, few therapeutic strategies aim to modulate this imbalance between Th17 and Treg cells in ITP. METHODS: ITP patients and healthy controls were enrolled in this study. Quantitative real-time PCR (qRT-PCR) and Western blotting were performed to measure the expression of the aryl hydrocarbon receptor (AhR), cytochrome P450 family 1 member A1 (CYP1A1), RAR-related orphan receptor gamma t (ROR-γt) and forkhead-box P3 (Foxp3). ELISA was employed to measure the secretion of IL-17A, IL-22 and IL-10. Flow cytometry was used to assess the proportion of Th17 and Treg cells. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to measure cell viability. RESULTS: The proportion of Th17 cells and the secretion of the pro-inflammatory cytokines IL-17A and IL-22 were both elevated, whereas the proportion of Treg cells and the production of the anti-inflammatory cytokine IL-10 were both reduced in ITP patients compared to healthy controls. The ratio of Th17/Treg cells and the expression of IL-17A and IL-22 displayed a positive correlation with the severity of ITP. Low and moderate concentrations of resveratrol did not affect the viability of CD4+ T cells from ITP patients but repressed Th17 differentiation and promoted Treg differentiation. Moreover, resveratrol could markedly downregulate the production of IL-17A and IL-22 and upregulate the secretion of IL-10 in CD4+ T cells in a time- and concentration-dependent manner. Mechanistic studies revealed that resveratrol exerted its beneficial function mainly through suppressing the AhR pathway, which led to the impaired expression of ROR-γt and reduced secretion of IL-17A and IL-22, as well as enhanced expression of Foxp3 and augmented secretion of IL-10. The induction of AhR by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in CD4+ T cells led to a Th17/Treg imbalance and the upregulation of IL-17A and IL-22, an effect that could be reversed by resveratrol treatment. CONCLUSION: This study revealed that resveratrol reversed the Th17/Treg imbalance by a mechanism involving the suppression of the AhR pathway. Since ITP is characterized by a Th17/Treg imbalance, resveratrol might be beneficial for the treatment of this condition.


Assuntos
Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Receptores de Hidrocarboneto Arílico/antagonistas & inibidores , Resveratrol/uso terapêutico , Linfócitos T Reguladores/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Adolescente , Adulto , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Citocinas/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/imunologia , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Resveratrol/farmacologia , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Adulto Jovem
17.
Int Immunopharmacol ; 72: 437-444, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31030100

RESUMO

BACKGROUND: Immune thrombocytopenia (ITP) is an immune-mediated acquired autoimmune hemorrhagic disease. About one-third of patients are unresponsive to first-line therapies. Thalidomide (THD) as an immunomodulatory agent is now used to treat several autoimmune disorders. Therefore, we assessed the safety and efficacy of THD in corticosteroid-resistant or relapsed ITP patients, and preliminarily explore its mechanism. METHODS: 50 newly-diagnosed ITP patients and 47 healthy volunteers were enrolled in this study. Additionally, 17 corticosteroid-resistant or relapsed ITP patients were recruited, with 7 cases in the rhTPO + THD group and 10 cases in the THD monotherapy group. Overall response rate at 6, 12, and 24 months were assessed. Levels of Neuropilin-1(NRP-1), regulatory T cells (Tregs) and regulatory B cells (Bregs) were detected. RESULTS: Expression of NRP-1, Tregs and Bregs were reduced in newly-diagnosed ITP patients. In vitro, THD treatment upregulated expression of NRP-1and Tregs only in ITP patients. As for corticosteroid-resistant or relapsed ITP patients, overall response rate at 6, 12, and 24 months was 85.7%, 57.1% and 100% in the rhTPO + THD group and 60%, 75% and 83.3% in the THD group, respectively. Additionally, rhTPO plus THD or THD therapy significantly increased the levels of NRP-1, Tregs and Bregs in responders. CONCLUSIONS: Our study shows for the first time that NRP-1 is involved in the pathogenesis of ITP, THD could induce response in ITP patients by upregulating NRP-1 expression and restoring the proportion of Tregs and Bregs. THD might be served as a novel therapeutic agent in corticosteroid-resistant or relapsed ITP patients.


Assuntos
Imunossupressores/uso terapêutico , Neuropilina-1/imunologia , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Talidomida/uso terapêutico , Adolescente , Corticosteroides/uso terapêutico , Adulto , Linfócitos B Reguladores/efeitos dos fármacos , Linfócitos B Reguladores/imunologia , Resistência a Medicamentos , Feminino , Humanos , Imunossupressores/farmacologia , Masculino , Pessoa de Meia-Idade , Neuropilina-1/genética , Púrpura Trombocitopênica Idiopática/genética , Púrpura Trombocitopênica Idiopática/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Talidomida/farmacologia , Regulação para Cima/efeitos dos fármacos , Adulto Jovem
18.
Zhonghua Xue Ye Xue Za Zhi ; 40(3): 191-194, 2019 Mar 14.
Artigo em Chinês | MEDLINE | ID: mdl-30929384

RESUMO

Objective: To evaluate the efficacy and safety of recombinant human thrombopoietin (rhTPO) treatment for primary immune thrombocytopenia (ITP) patients during the perioperative period. Methods: Adult ITP patients who were refractory to first-line glucocorticoid therapy and underwent selective surgery were enrolled to be treated with rhTPO at the dosage of 1.5×10(4)U/d subcutaneously during the perioperative period. rhTPO treatment would not be terminated until one of the following conditions occurred: ①Platelet counts met the requirement of surgery; ②Platelet counts were ≥100×10(9)/L; ③Completed the 14 days of therapy. End points of the study were surgery rate, rhTPO therapy response rate, rescue therapy rate and adverse responses. Results: 42 patients were enrolled from Jan. 1, 2016 to Jun. 30, 2018. 14 were male and 28 were female. The median age was 60 (25-73) years old. There were no newly diagnosed patients. 5 patients were persistent and 37 were chronic. 27 patients completed selective surgery. The surgery rate was 64.3% (27/42) . Among them, 13 patients were under local anesthesia and 14 under general anesthesia. Of 42 cases receiving rhTPO therapy. 31 patients achieved responses, The overall response rate was of 73.8%. Among them, 24 patients achieved CR. The CR ratio was 77.4% (24/31) . 7 achieved response. The response ratio was 22.6% (7/31) . 11 patients did not respond to rhTPO therapy. The non-response rate was 26.2% (11/42) . The median time to reach CR was 7 (3-16) days. The median time to reach the peak of platelet counts were 10 (3-21) days. rhTPO was used for a median of 7 (3-14) days. The median platelet counts of patients undergoing surgery before rhTPO therapy, before surgery and at day 7 after surgery were 33 (20-89) ×10(9)/L, 125 (78-245) ×10(9)/L and 72 (30-250) ×10(9)/L, respectively. The median peak of platelet counts was 149 (101-466) ×10(9)/L. No infection, bleeding, thromboembolism and therapy-related adverse responses occurred in the patients. Conclusion: rhTPO for ITP patients during the perioperative period is safe and effective.


Assuntos
Púrpura Trombocitopênica Idiopática , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Perioperatório , Contagem de Plaquetas , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Proteínas Recombinantes , Trombopoetina/uso terapêutico
19.
Exp Hematol ; 73: 18-24, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31014934

RESUMO

Indirubin, a traditional Chinese medicine, is currently used to treat certain autoimmune diseases such as primary immune thrombocytopenia (ITP) in clinics. However, the effects of indirubin on expression of related genes in peripheral blood mononuclear cells (PBMCs) from ITP patients have not been investigated. In the present study, PBMCs were isolated from 19 adult patients with well-characterized active ITP and 20 healthy controls (HCs) and then treated with increasing concentrations of indirubin. The mRNA expression levels of thrombopoietin receptor (MPL), GATA binding protein 3 (GATA3), DNA methyltransferase 3B (DNMT3B), interleukin-6 (IL6), tumor necrosis factor (TNF), and interferon gamma (IFN-γ) were determined by quantitative real-time polymerase chain reaction (PCR). We found that indirubin had no cytotoxic effect on PBMC viability. Significantly lower MPL (p < 0.05) and GATA3 (p < 0.05) expression together with markedly higher IL6 (p < 0.05), TNF (p < 0.0001), and IFN-γ (p < 0.001) mRNA levels were observed in ITP patients compared with HCs. Notably, indirubin significantly enhanced MPL expression and inhibited TNF expression in PBMCs from ITP patients (p < 0.05). In summary, indirubin may play a direct role in thrombopoiesis by activating cellular MPL and normalizing TNF expression to suppress inflammation in ITP. This study may thus improve our understanding of indirubin and provide important information for optimizing therapeutic strategies for ITP patients.


Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Púrpura Trombocitopênica Idiopática , Receptores de Trombopoetina/sangue , Fator de Necrose Tumoral alfa/sangue , Adulto , Idoso , DNA (Citosina-5-)-Metiltransferases/sangue , Feminino , Fator de Transcrição GATA3/sangue , Humanos , Indóis/administração & dosagem , Interferon gama/sangue , Interleucina-6/sangue , Leucócitos Mononucleares/patologia , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/patologia
20.
Am J Health Syst Pharm ; 76(11): 789-794, 2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-30951590

RESUMO

PURPOSE: The pharmacology, pharmacokinetics, efficacy, safety, dosing and administration, and place in therapy of fostamatinib, a novel spleen tyrosine kinase inhibitor for the treatment of adult immune thrombocytopenia that has had an insufficient response to a previous treatment are summarized. SUMMARY: Fostamatinib is an oral inhibitor of spleen tyrosine kinase that is expressed on hematopoietic cells and plays a key role in the accelerated destruction of platelets through Fc-receptor activation. Fostamatinib is indicated for the treatment of adults with immune thrombocytopenia that has had an insufficient response to a previous treatment. In 2 parallel, identically designed, placebo-controlled Phase III trials, patients with persistent and chronic immune thrombocytopenia treated with fostamatinib demonstrated clinically meaningful responses in platelet counts with lower rates of moderate and severe bleeding-related adverse events. Overall, fostamatinib therapy is generally well tolerated; the most common adverse events reported in clinical trials were diarrhea, nausea, hypertension, liver function test elevations, and infection. Being primarily metabolized through the CYP3A4 pathway, fostamatinib is subject to drug-drug interactions and concomitant administration with strong CYP3A4 inhibitors or inducers can affect fostamatinib exposure. CONCLUSION: Fostamatinib is a first-in-class spleen tyrosine kinase inhibitor approved for the treatment of adults with immune thrombocytopenia that has had an insufficient response to a previous treatment.


Assuntos
Plaquetas/efeitos dos fármacos , Oxazinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Piridinas/farmacologia , Quinase Syk/antagonistas & inibidores , Administração Oral , Plaquetas/imunologia , Ensaios Clínicos Fase III como Assunto , Relação Dose-Resposta a Droga , Humanos , Oxazinas/uso terapêutico , Contagem de Plaquetas , Inibidores de Proteínas Quinases/uso terapêutico , Púrpura Trombocitopênica Idiopática/imunologia , Piridinas/uso terapêutico , Receptores Fc/imunologia , Receptores Fc/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Quinase Syk/metabolismo , Resultado do Tratamento
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