Indirubin regulates MPL and TNF expression in peripheral blood mononuclear cells from patients with primary immune thrombocytopenia.

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.

High dose dexamethasone as an alternative rescue therapy for active bleeding in children with chronic ITP: clinical and immunological effects.

High-dose dexamethasone (HD-DXM) is debated as a second-line therapy for chronic Immune thrombocytopenia (ITP) in children. The aim of this study is to evaluate the efficacy and safety of HD-DXM as an emergency therapy in uncontrolled bleeding in children with chronic ITP and to assess its immunological effect on dendritic cells (DCs) percentage and their co-stimulatory markers CD86 and CD83. Totally, 20 children previously diagnosed as chronic ITP were enrolled in this study and all admitted to hospital with uncontrolled bleeding. Patients received HD-DXM as a single daily dose for 4 days. Blood samples were withdrawn from patients just prior to HD-DXM therapy and on day 5 to evaluate the platelet count and for flowcytometric analysis of DCs. Daily assessment of bleeding severity was performed. The platelet counts significantly increased in patients after 5 days of initiation of therapy compared with platelet count before therapy (p-value = 0. 0002). Control of bleeding observed in (90%), complete response (CR) documented in (50%), response (R) documented in (40%), and no response (NR) documented in (10%) of patients. The time to respond was raging from 1 to 3 days and minor complication recorded in two patients. Both plasmacytoid DCs and myeloid DCs percentage and their expression of co-stimulatory markers, CD86 and CD83 decreased significantly after HD-DXM therapy. Conclusion: short course of HD-DXM as a rescue therapy seems to be an effective alternative emergency treatment for uncontrolled bleeding in chronic ITP children especially in nations with limited resources.

Pharmacological agents preceding a diagnosis of immune thrombocytopenia in adult patients developing the chronic form: A Swedish national register study.

Patients with primary chronic immune thrombocytopenia (cITP) have been reported to use more anti-infective medications, even before diagnosis of immune thrombocytopenia (ITP). The more common use of anti-infective medications may be due to general health problems, requiring medication in the early stages of cITP and before the diagnosis is set, rather than infections preceding the disease. Accordingly, cITP may not only be associated with use of anti-infective medications but also with medications for more general symptoms. OBJECTIVE: To investigate use of medications for general symptoms, such as analgesics and vitamin supplements in patients with ITP developing the chronic form, the year preceding their first primary diagnosis in comparison with such use in the general population. METHOD: Swedish Health Registers were used to identify adult patients (n=1087) with primary cITP during 2006-2012 and data on medications. Standardized Incidence Ratios (SIRs) and 95% confidence intervals (CI), were estimated as a measure of relative risk. RESULTS: The association for overall studied medications was SIR=1.36 (95% CI 1.32-1.41). A majority of the point estimates were above unity. CONCLUSION: In patients with cITP, prescription fills for medications used to treat pain conditions and vitamin deficiencies are more common in the year preceding their first diagnosis as compared with prescription fills in the general population. Our results suggest that patients later diagnosed with cITP receive treatment due to symptoms that could be signs of an early ITP. Accordingly, in investigations for unspecific pain symptoms and vitamin deficiencies, cITP should be considered as a differential diagnosis.

[The endoscopic and clinical features of Indigo Naturalis-associated ischemic lesions of colonic mucosa].

OBJECTIVE: By analysing the clinical features of Indigo Naturalis-associated ischemic lesion of colon mucosa to improve the precautionary and therapeutic level of the disease. METHODS: Thirteen patients diagnosed as Indigo Naturalis-associated ischemic lesion of colon mucosa in Peking University Third Hospital from 2005 to 2010 were reviewed. The endoscopic and clinical features were analysed. RESULTS: The 13 patients with an average age of (60.6 ± 14.1) years old were prescribed Chinese traditional medicine containing Indigo Naturalis for psoriasis or idiopathic thrombocytopenic purpura (ITP). The ratio of males to females was 1:1.6. The typical manifestations were abdominal pain and bloody stool with watering diarrhea before bloody stool in 61.5% patients. Endoscopic and pathological characteristics were coincident with ischemic lesion and more like a chronic index. Vasodilatic medicine was effective and the average hemostatic time was (1.7 ± 0.8) days. The prognosis was well and no recurrence was found during 3 months follow-up. CONCLUSIONS: Patients having psoriasis or ITP treated with Chinese traditional medicine containing Indigo Naturalis have an inclination to colon mucosa lesions, even ischemic lesion. Careful assessment and observation before prescribing are necessary in these patients.

Clinical study on the effect of Shengxueling on idiopathic thrombocytopenic purpura.

OBJECTIVE: To observe the clinical effect of Shengxueling (SXL) on idiopathic thrombocytopenic purpura (ITP), and study the possible mechanism. METHODS: Eighty-six cases of ITP were randomly divided into two groups. The SXL group, 56 patients treated with SXL, a traditinal Chinese medicine and 30 patients administered with prednisone were taken as control. Each group took drugs for 3 months and was under follow-up observation. RESULTS: In the SXL group, the total effective rate was 85.71%, similar to prednisone 83.33% (P > 0.05) for 3 months, but the total effective rate of SXL (91.07%) were obviously better than that of the control group (53.33%) (P < 0.01) for 6 months and had no obvious adverse reaction. The patients bleeding was alleviated or stopped, the general condition was improved. At the same time, blood platelet count (PLT) was increased, platelet associated immunoglobulin (PAIg) and interleukin-4 (IL-4) were markedly dropped, the level of natural killers cells activity (NKa) increased, the rate of T lymphocyte subsets gradually returned to normal level. Megakaryocyte tended to maturation on bone marrow smear after treatment. All differences above were statistically significant. CONCLUSION: SXL is an effective and safe medicine for ITP. Its mechanism could regulate cytoimmune, inhibit platelet antibody to reduce the destruction of platelet, increase the number of platelet, promote the division and maturation of megakaryocyte, facilitate the production and release of platelet, lower the fragility of capillary, prevent and cure hemorrhagic tendency.

Reduced bone mineral density in childhood chronic idiopathic thrombocytopenic purpura treated with high-dose methylprednisolone.

PURPOSE: To evaluate whether repeated courses of high-dose methylprednisolone (HDMP) affect the lumbar spine bone mineral density (BMD) in children with chronic idiopathic thrombocytopenic purpura (ITP). MATERIALS AND METHODS: This study included 24 patients with chronic ITP and 149 healthy controls. The patients were allocated into three groups according to the number of HDMP courses (30 mg/kg per day as a single dose for 7 days); group 1 (10 patients), group 2 (9 patients), and group 3 (5 patients) had received less than 5, 6-10, and more than 10 courses, respectively. Lumbar spine BMD and body composition were measured using dual energy X-ray absorptiometry of lumbar spine (L2-L4), and volumetric bone mineral density (vBMD) values were calculated and compared with the controls. The z score of the vBMD was also calculated and compared in the patients of each other groups. Serum markers of the bone turnover were measured to exclude other factors that could effect BMD. RESULTS: The vBMD values of the patients, corrected BMDs for age, were significantly lower than the values of controls (P = 0.018). It was significantly lower in group 3 than groups 1 and 2 (P = 0.005 and P = 0.006, respectively), but there was no statistically significant difference between groups 1 and 2 (P = 0.87). The vBMD z scores were significantly lower in group 3 than in groups 1 and 2 (P = 0.003 and P = 0.004, respectively), and also in group 2 than in group 1 (P = 0.034). There were a weak negative correlation between the cumulative dose of HDMP and vBMD (r = -0.39, P = 0.054), and strong negative correlation between the cumulative dose of HDMP and vBMD z score (r = -0.63, P = 0.001). CONCLUSION: Children with chronic ITP are at risk for decreased BMD because of the repeated courses of HDMP; especially more than 2100 mg of cumulative dose. We therefore recommend that BMD should be monitored in patients with chronic ITP who received repeated courses of HDMP.

Using decision analysis techniques to deal with "unanswerable" questions in idiopathic thrombocytopenic purpura.

Idiopathic thrombocytopenic purpura (ITP) is a common disorder with rare adverse outcomes. This makes it a particularly difficult area in which to undertake conventional studies. An alternative method for solving clinical questions is decision analysis, which is in essence a computer-assisted synthesis of the literature. Using the example of a newly diagnosed ITP patient, the author attempts to answer the question of whether a bone marrow aspirate (BMA) is required prior to starting steroids. Using decision analysis methodology, the author determines that BMA is not essential prior to starting steroids. More importantly, three variables critical to the decision-making process are determined: the risk of death from the BMA procedure, the altered chance of survival for a patient with acute lymphoblastic leukemia (ALL) inappropriately given steroids, and how sensitive the complete blood count is at determining the risk of ALL. This scenario demonstrates the value of decision analysis and lays the groundwork for future endeavors.

[Immune cytopenias in newborns]. / Cytopénies immunes néonatales.

Rhesus D haemolytic disease of the newborn (RH HDN) and neonatal PlA1 alloimmune thrombocytopenia (NAT) are the main immune cytopenias affecting fetal red blood cells or platelets through maternal antibodies. During RH HDN, fetal anaemia and neonatal hyperbilirubinaemia may progress, if untreated, towards fetal death and neonatal kernicterus. Likewise, during NAT, intracranial haemorrhage may occur antenally, at delivery or postnatally. Fetal and neonatal transfusion therapy, pre-term delivery, and intensive phototherapy avoid or greatly reduce the incidence of these complications. However, the best treatment of RH HDN is to prevent primary anti-D immunisation in Rh negative pregnant women through passive immunotherapy with Rh immune globulin.