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1.
J Surg Res ; 245: 643-648, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31536907

RESUMEN

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.


Asunto(s)
Púrpura Trombocitopénica Idiopática/cirugía , Esplenectomía/métodos , Corticoesteroides/uso terapéutico , Adulto , Anciano , Femenino , Humanos , Laparoscopía , Masculino , Persona de Mediana Edad , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Estudios Retrospectivos , Esplenectomía/efectos adversos
2.
Ann Hematol ; 98(11): 2497-2506, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31595308

RESUMEN

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.


Asunto(s)
Proteínas Adaptadoras de Señalización CARD/genética , Polimorfismo de Nucleótido Simple , Púrpura Trombocitopénica Idiopática/genética , Corticoesteroides/uso terapéutico , Adulto , Alelos , Proteínas Adaptadoras de Señalización CARD/fisiología , Estudios de Casos y Controles , Resistencia a Medicamentos , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Riesgo
3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1602-1606, 2019 Oct.
Artículo en Chino | MEDLINE | ID: mdl-31607319

RESUMEN

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.


Asunto(s)
Púrpura Trombocitopénica Idiopática , Rituximab/uso terapéutico , Dexametasona , Glucocorticoides , Humanos , Inosina Trifosfato , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico
5.
Int J Immunopathol Pharmacol ; 33: 2058738419872120, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31438744

RESUMEN

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.


Asunto(s)
Benzoatos/efectos adversos , Benzoatos/uso terapéutico , Enfermedad Crónica/tratamiento farmacológico , Hidrazinas/efectos adversos , Hidrazinas/uso terapéutico , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Pirazoles/efectos adversos , Pirazoles/uso terapéutico , Adolescente , Niño , Preescolar , China , Femenino , Humanos , Lactante , Masculino , Recuento de Plaquetas/métodos , Resultado del Tratamiento
6.
Acta Dermatovenerol Croat ; 27(2): 121-123, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31351508

RESUMEN

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.


Asunto(s)
Adalimumab/uso terapéutico , Psoriasis/tratamiento farmacológico , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Adolescente , Femenino , Humanos , Calidad de Vida , Inducción de Remisión
7.
Drugs ; 79(12): 1305-1319, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31292909

RESUMEN

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.


Asunto(s)
Anemia Aplásica/tratamiento farmacológico , Benzoatos/uso terapéutico , Hidrazinas/uso terapéutico , Megacariocitos/inmunología , Síndromes Mielodisplásicos/tratamiento farmacológico , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Pirazoles/uso terapéutico , Benzoatos/administración & dosificación , Benzoatos/efectos adversos , Humanos , Hidrazinas/administración & dosificación , Hidrazinas/efectos adversos , Inmunomodulación , Inmunosupresión , Púrpura Trombocitopénica Idiopática/inmunología , Pirazoles/administración & dosificación , Pirazoles/efectos adversos , Receptores de Trombopoyetina/agonistas
8.
Chin J Integr Med ; 25(7): 483-489, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31278626

RESUMEN

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.


Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Inmunidad Celular , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Púrpura Trombocitopénica Idiopática/inmunología , Investigación , Hemorragia/tratamiento farmacológico , Humanos
9.
Blood Coagul Fibrinolysis ; 30(6): 295-299, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31259778

RESUMEN

: 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.


Asunto(s)
Benzoatos/uso terapéutico , Hidrazinas/uso terapéutico , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Pirazoles/uso terapéutico , Receptores Fc/uso terapéutico , Receptores de Trombopoyetina/agonistas , Proteínas Recombinantes de Fusión/uso terapéutico , Trombopoyetina/uso terapéutico , Corticoesteroides/farmacología , Enfermedad Crónica , Resistencia a Medicamentos , Femenino , Humanos , Inmunoglobulinas Intravenosas/farmacología , Masculino , Púrpura Trombocitopénica Idiopática/cirugía , Esplenectomía
10.
Rinsho Ketsueki ; 60(5): 480-487, 2019.
Artículo en Japonés | MEDLINE | ID: mdl-31168017

RESUMEN

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.


Asunto(s)
Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Púrpura Trombocitopénica Trombótica/tratamiento farmacológico , Rituximab/uso terapéutico , Proteína ADAMTS13/antagonistas & inhibidores , Ensayos Clínicos como Asunto , Humanos , Japón , Intercambio Plasmático
11.
Ann Hematol ; 98(8): 1845-1854, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31154474

RESUMEN

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.


Asunto(s)
Apirasa/genética , Dexametasona/uso terapéutico , Inmunosupresores/uso terapéutico , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Receptor de Adenosina A2A/genética , Linfocitos T Reguladores/efectos de los fármacos , Adenosina/inmunología , Adenosina/metabolismo , Adenosina Trifosfato/inmunología , Adenosina Trifosfato/metabolismo , Adulto , Anciano , Apirasa/inmunología , Estudios de Casos y Controles , Femenino , Expresión Génica , Humanos , Inmunofenotipificación , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Púrpura Trombocitopénica Idiopática/enzimología , Púrpura Trombocitopénica Idiopática/genética , Púrpura Trombocitopénica Idiopática/inmunología , Receptor de Adenosina A2A/inmunología , Linfocitos T Citotóxicos/efectos de los fármacos , Linfocitos T Citotóxicos/enzimología , Linfocitos T Citotóxicos/inmunología , Linfocitos T Reguladores/enzimología , Linfocitos T Reguladores/inmunología
12.
Transfus Apher Sci ; 58(4): 491-494, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31105060

RESUMEN

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.


Asunto(s)
Inmunoglobulinas Intravenosas/administración & dosificación , Auditoría Médica , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Administración Intravenosa , Adulto , Canadá/epidemiología , Femenino , Humanos , Masculino , Púrpura Trombocitopénica Idiopática/sangre , Púrpura Trombocitopénica Idiopática/epidemiología , Estudios Retrospectivos
13.
Int Immunopharmacol ; 73: 181-192, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31102993

RESUMEN

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.


Asunto(s)
Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Receptores de Hidrocarburo de Aril/antagonistas & inhibidores , Resveratrol/uso terapéutico , Linfocitos T Reguladores/efectos de los fármacos , Células Th17/efectos de los fármacos , Adolescente , Adulto , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Citocinas/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Púrpura Trombocitopénica Idiopática/inmunología , Receptores de Hidrocarburo de Aril/genética , Receptores de Hidrocarburo de Aril/metabolismo , Resveratrol/farmacología , Linfocitos T Reguladores/inmunología , Células Th17/inmunología , Adulto Joven
14.
Medicine (Baltimore) ; 98(16): e15195, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31008943

RESUMEN

This study evaluated the effectiveness of recombinant human interleukin-11 (rhIL-11) in the treatment of immune thrombocytopenia (ITP) and determined whether clinical and laboratory findings predicted the treatment response.This retrospective, single-center, case-control study included 103 adult patients with ITP treated between July 2010 and April 2014 at Jiangxi Province People's Hospital. About 49 patients in the pred+IL group received prednisone (conventional dose) combined with an rhIL-11 regimen, and 54 patients in the pred alone group received prednisone (conventional dose) alone. Demographic data, initial and follow-up platelet counts, proportions of patients achieving platelet counts ≥30 × 10/L (response) and ≥100 × 10/L (complete response) at different time points, and adverse reactions were compared between groups.Complete response rates were similar between groups overall but higher in the pred+IL group than in the pred alone group for newly diagnosed patients and those with severe ITP (P < .05). Proportions of patients achieving response or complete response at different time points were similar between groups overall but higher in the pred+IL group than in the pred alone group for newly diagnosed patients and those with severe ITP (P < .05). Posttreatment platelet count correlated negatively with platelet count at diagnosis and white blood cell (WBC) count at diagnosis in patients with newly diagnosed ITP (r = -0.337, P = .073 and r = -0.367, P = .050, respectively) or ITP with bleeding-related episodes (r = -0.357, P = .020 and r = -0.434, P = .004, respectively). No immediate or postinfusion severe adverse reactions were observed.rhIL-11 increased CR and improved hemostasis in patients with newly diagnosed or severe ITP. Platelet and WBC counts at diagnosis can predict the response to rhIL-11.


Asunto(s)
Antineoplásicos/uso terapéutico , Interleucina-11/uso terapéutico , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Adolescente , Adulto , Anciano , Femenino , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Prednisona/uso terapéutico , Púrpura Trombocitopénica Idiopática/sangre , Proteínas Recombinantes/uso terapéutico , Estudios Retrospectivos , Adulto Joven
15.
Int Immunopharmacol ; 72: 437-444, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31030100

RESUMEN

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.


Asunto(s)
Inmunosupresores/uso terapéutico , Neuropilina-1/inmunología , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Talidomida/uso terapéutico , Adolescente , Corticoesteroides/uso terapéutico , Adulto , Linfocitos B Reguladores/efectos de los fármacos , Linfocitos B Reguladores/inmunología , Resistencia a Medicamentos , Femenino , Humanos , Inmunosupresores/farmacología , Masculino , Persona de Mediana Edad , Neuropilina-1/genética , Púrpura Trombocitopénica Idiopática/genética , Púrpura Trombocitopénica Idiopática/inmunología , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/inmunología , Talidomida/farmacología , Regulación hacia Arriba/efectos de los fármacos , Adulto Joven
16.
Int J Hematol ; 110(2): 255-259, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30972617

RESUMEN

A proportion of patients with immune thrombocytopenic purpura are refractory to multiple therapies including thrombopoietin-receptor agonists (TPO-RA). We report 10 patients who did not respond to a TPO-RA until the addition of a glucocorticoid. These patients were previously treated with a median of 6 therapies. One patient elected to discontinue both medications despite persistent thrombocytopenia. The remaining 9 patients continued on the combination of prednisone (doses 5 mg every other day to 10 mg daily) and a TPO-RA. Combination therapy with low dose glucocorticoid and a TPO-RA may be an option for patients unresponsive to a TPO-RA alone.


Asunto(s)
Benzoatos/uso terapéutico , Hidrazinas/uso terapéutico , Prednisona/uso terapéutico , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Pirazoles/uso terapéutico , Receptores Fc/uso terapéutico , Receptores de Trombopoyetina/antagonistas & inhibidores , Proteínas Recombinantes de Fusión/uso terapéutico , Trombopoyetina/uso terapéutico , Adolescente , Adulto , Anciano , Benzoatos/administración & dosificación , Benzoatos/efectos adversos , Benzoatos/farmacología , Preescolar , Terapia Combinada , Sinergismo Farmacológico , Quimioterapia Combinada , Femenino , Humanos , Hidrazinas/administración & dosificación , Hidrazinas/efectos adversos , Hidrazinas/farmacología , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Prednisona/administración & dosificación , Prednisona/efectos adversos , Prednisona/farmacología , Púrpura Trombocitopénica Idiopática/cirugía , Pirazoles/administración & dosificación , Pirazoles/efectos adversos , Pirazoles/farmacología , Receptores Fc/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/efectos adversos , Proteínas Recombinantes de Fusión/farmacología , Esplenectomía , Trombopoyetina/administración & dosificación , Trombopoyetina/efectos adversos , Trombopoyetina/farmacología
17.
Zhonghua Xue Ye Xue Za Zhi ; 40(3): 191-194, 2019 Mar 14.
Artículo en Chino | MEDLINE | ID: mdl-30929384

RESUMEN

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.


Asunto(s)
Púrpura Trombocitopénica Idiopática , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Periodo Perioperatorio , Recuento de Plaquetas , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Proteínas Recombinantes , Trombopoyetina/uso terapéutico
18.
Am J Health Syst Pharm ; 76(11): 789-794, 2019 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-30951590

RESUMEN

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.


Asunto(s)
Plaquetas/efectos de los fármacos , Oxazinas/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Piridinas/farmacología , Quinasa Syk/antagonistas & inhibidores , Administración Oral , Plaquetas/inmunología , Ensayos Clínicos Fase III como Asunto , Relación Dosis-Respuesta a Droga , Humanos , Oxazinas/uso terapéutico , Recuento de Plaquetas , Inhibidores de Proteínas Quinasas/uso terapéutico , Púrpura Trombocitopénica Idiopática/inmunología , Piridinas/uso terapéutico , Receptores Fc/inmunología , Receptores Fc/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunología , Quinasa Syk/metabolismo , Resultado del Tratamiento
19.
Int J Mycobacteriol ; 8(1): 107-109, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30860190

RESUMEN

Pulmonary tuberculosis can have a wide variety of presentations including hematological manifestations. We report a case of a young male patient who presented with complaints of generalized petechiae, gum bleeding, systemic lymphadenopathy, and severe thrombocytopenia. His bone marrow revealed normal megakaryocytes, and in the absence of hepatosplenomegaly, a diagnosis of immune thrombocytopenic purpura (ITP) was made. The thrombocytopenia responded to course of intravenous immune globulin. The smear made from fine-needle aspiration of cervical lymph nodes showed acid-fast bacilli. This case highlights the rare association of extrapulmonary tuberculosis with ITP.


Asunto(s)
Púrpura Trombocitopénica Idiopática/diagnóstico , Púrpura Trombocitopénica Idiopática/patología , Tuberculosis/complicaciones , Biopsia con Aguja Fina , Humanos , Inmunoglobulinas Intravenosas/administración & dosificación , Linfocitos/microbiología , Linfocitos/patología , Masculino , Microscopía , Mycobacterium tuberculosis/aislamiento & purificación , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Resultado del Tratamiento , Adulto Joven
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