Oxidant/antioxidant status in children and adolescents with immune thrombocytopenia (ITP) and the role of an adjuvant antioxidant therapy.

BACKGROUND: Free oxygen radicals might have an adverse effect on platelets which might be reflected either on its count and/or degree of bleeding severity. AIM: To assess oxidant-antioxidant systems and evaluate effect of antioxidant therapy on platelet count (PC) and bleeding score (BS) in children and adolescents with ITP. METHODS: Six months prospective randomized single blind study registered as (NCT 01763658) including 39 patients with newly diagnosed (ND) ITP; group 1 (G1) and 39 patients with chronic ITP (G2), each group was randomly allocated (2:1) to one of two subgroups respectively; (G1A and G2A) interventional arm received daily antioxidant therapy, while G1B and G2B; received a placebo. Both groups were compared with healthy controls (n = 39). The primary efficacy endpoints were the difference in the change from baseline to 6 month in ITP specific bleeding assessment tool (ITP-BAT), PC, total antioxidant capacity (TAC), catalase (CAT), reduced glutathione (GSH) and serum malondialdehyde (MDA). RESULTS: Baseline TAC was significantly lower in patients with (ND) ITP compared to patients with chronic ITP (P < 0.05), both showed significantly lower levels than healthy controls (P < 0.001). At end of study both BS and PC significantly improved in patients receiving antioxidant compared to placebo (P < 0.05). Patients with chronic ITP receiving antioxidant showed better improvement. CONCLUSION: Reduced antioxidant mechanisms were reported in patients with ITP. Antioxidant therapy ameliorated the oxidative stress in both ND and chronic ITP groups which might explain the improvement in both BS and PC.

Type and intensity of FVIII exposure on inhibitor development in PUPs with haemophilia A. A patient-level meta-analysis.

The impact of treatment-related factors on inhibitor development in previously untreated patients (PUPs) with haemophilia A is still debated. We present the results of a collaborative, individual patient data meta-analytic project. Eligible data sources were published cohorts of PUPs for which patient-level data were available. The exposures of interest were factor (F)VIII type (recombinant [rFVIII] vs plasma-derived [pdFVIII]) and treatment intensity (≥ vs < 150 IU/kg/week) at first treatment. Family history of inhibitors, F8 mutations, age, treatment regimen (on-demand vs prophylaxis), secular trend and surgery were analysed as putative confounders using different statistical approaches (multivariable Cox regression, propensity score analyses, CART). Analyses accounted for the multi-centre origin of the data. We included 761 consecutive, unselected PUPs with moderate to severe haemophilia A from 10 centres in Egypt, Germany, Israel and Italy. A total of 27 % of patients developed inhibitors; 40 % and 22 % of patients treated with rFVIII and pdFVIII (unadjusted HR 2.2, 95 % CI 1.6-2.9), respectively; 51 % and 24 % of patients receiving high- and low-intensity treatment (unadjusted HR 2.9, 95 % CI 2.0-4.2), respectively. In adjusted analyses, only treatment intensity remained an independent predictor; the effect of FVIII type was largely due to confounding, but with a significant interaction between FVIII type and treatment intensity. This patient-level meta-analysis confirms, across different statistical approaches, that high-intensity treatment is a strong risk factor for inhibitor development. The possible role of FVIII type in subgroups is suggested by the test for interactions but could not be proven because of the limited subgroups sample sizes.

Deviating from safety guidelines during deferiprone therapy in clinical practice may not be associated with higher risk of agranulocytosis.

BACKGROUND: A risk associated with the iron chelator deferiprone is the development of neutropenia or agranulocytosis. Accordingly, the product label recommends weekly blood monitoring and immediate interruption of treatment upon detection of an absolute neutrophil count (ANC) <1.5 × 10(9)/L, out of concern that continued therapy might lead to a more severe drop. However, it is uncertain how these recommendations are followed under real-life conditions and, if they are not followed, whether continuation of therapy results in increased incidence of agranulocytosis. PROCEDURE: This non-interventional surveillance program assessed the monitoring of deferiprone therapy in clinical practice. A total of 294 patients with transfusion-dependent anemias received deferiprone, as monotherapy or with another chelator, for up to 1 year. The participating physicians were not given any instructions about treatment and monitoring beyond being referred to the information in the package insert. RESULTS: ANC monitoring was conducted at an average interval of 5 ± 4 weeks, and deferiprone was not always interrupted upon detection of neutropenia. One patient (0.3%) experienced agranulocytosis, and nine others (3%) experienced a total of 11 episodes of neutropenia. All neutropenia episodes resolved; median time to resolution was similar whether or not treatment was interrupted; and no case of neutropenia progressed to agranulocytosis. CONCLUSIONS: These data indicate that less frequent ANC monitoring and continuation of deferiprone therapy during neutropenia are not associated with prolonged neutropenia or with progression to agranulocytosis.

Predictors of chronic idiopathic thrombocytopenic purpura.

BACKGROUND: Idiopathic thrombocytopenic purpura is a hematological disorder with heterogeneous manifestation and unpredictable outcome. This study reviewed the pattern of presentation and response to therapy in patients with ITP, in order to identify risk factors for chronic disease. PROCEDURE: The study included all patients diagnosed as ITP between January 1998 and December 2007. RESULTS: Sixty-five percent of the patients had acute and 34.9% had chronic ITP. Patients with chronic ITP had a higher mean age at diagnosis (P = 0.0000003). Females more than 10 years of age were more susceptible than males to follow a chronic course (P = 0.031). Febrile illness preceded the onset of ITP in 167 patients, 76.0% of them had an acute course (P = 0.000037). Moderate and severe bleeding occurred in 11.34% and 7.27% of the patients, respectively. Fifty-four patients (15.7%) improved without any specific treatment. Corticosteroids were used as a first-line treatment in 209 patients and showed a total response of 76.6% compared to 85.7% and 84% for IVIG and anti-D immunoglobulin treated patients, respectively. CONCLUSION: The most relevant risk factors for the development of chronic ITP included a gradual mode of onset of symptoms over more than 2 weeks period, initial platelet count >20 x 10(9)/L, and age more than 10 years at presentation.