Immune Thrombocytopenia in Children Less Than 1 Year of Age: A Single-institution 10-year Experience.
Journal of pediatric hematology/oncology
2013; 35 (5): 406-408
A novel splice donor mutation in the thrombopoietin gene leads to exon 2 skipping in a Filipino family with hereditary thrombocythemia
2011; 118 (26): 6988-?
The role of vanin-1 and oxidative stress-related pathways in distinguishing acute and chronic pediatric ITP
2011; 117 (17): 4569-4579
Immune thrombocytopenia (ITP) in children less than one year of age is less well characterized compared to ITP in toddlers and school-age children. We performed a 10-year retrospective review of ITP patients in this age-cohort at our institution. Diagnosis and classification were made according to the 2009 International Working Group criteria. Fourteen infants were identified. Their bleeding scores were Grades 1 to 2 (79%), Grade 3 (22%), Grades 4 to 5 (0%). Eight patients received treatment with a 75% response rate. Three patients (21%) developed chronic ITP. These observations suggest that ITP in very young patients is similar to typical childhood ITP.
View details for DOI 10.1097/MPH.0b013e3182580ab4
View details for PubMedID 22767132
Monthly recombinant tissue plasminogen activator administration to implantable central venous access devices decreases infections in children with haemophilia
2009; 15 (6): 1272-1280
Pediatric immune thrombocytopenia (ITP) is usually self-limited. However, approximately 20% of children develop chronic ITP, which can be associated with significant morbidity because of long-term immunosuppression and splenectomy in refractory cases. To explore the molecular mechanism of chronic ITP compared with acute ITP, we studied 63 pediatric patients with ITP. Gene expression analysis of whole blood revealed distinct signatures for acute and chronic ITP. Oxidative stress-related pathways were among the most significant chronic ITP-associated pathways. Overexpression of VNN1, an oxidative stress sensor in epithelial cells, was most strongly associated with progression to chronic ITP. Studies of normal persons demonstrated VNN1 expression in a variety of blood cells. Exposure of blood mononuclear cells to oxidative stress inducers elicited dramatic up-regulation of VNN1 and down-regulation of PPAR?, indicating a role for VNN1 as a peripheral blood oxidative stress sensor. Assessment of redox state by tandem mass spectrometry demonstrated statistically significant lower glutathione ratios in patients with ITP versus healthy controls; lower glutathione ratios were also seen in untreated patients with ITP compared with recently treated patients. Our work demonstrates distinct patterns of gene expression in acute and chronic ITP and implicates oxidative stress pathways in the pathogenesis of chronic pediatric ITP.
View details for DOI 10.1182/blood-2010-09-304931
View details for PubMedID 21325602
Idiopathic neutropenia of childhood is associated with Fas/FasL expression
2008; 129 (3): 438-447
Central venous access devices (CVAD) have been effectively used in the care of haemophilia patients. This is particularly true in children, who often have difficult venous access. CVAD complications (infection and thrombosis), risk factors, and complication rates, have been well-documented. However, effective interventions which decrease complication rates have not been identified. In this study, we review our experience with the use of monthly recombinant tissue plasminogen activator (rtPA) administration in haemophilia patients with fully implanted CVADs. Data on 19 haemophilia patients with 24 CVADs were available for analysis, with a total of 24 520 CVAD days. An infection rate of 0.04 infections per 1000 CVAD days and a thrombosis rate of 0.04 thrombi per 1000 CVAD days was observed. The observed infectious complication rate is at least one logarithm lower than many published CVAD infection rates in haemophilia patients who have not received rtPA administration. No bleeding complications were noted. Monthly rtPA is safe and appears to be effective in decreasing CVAD infection rates. Larger, randomized controlled studies are indicated to validate this finding.
View details for DOI 10.1111/j.1365-2516.2009.02063.x
View details for PubMedID 19601989
SAFETY OF HEMATOPOIETIC STEM CELL TRANSPLANTATION IN CHILDREN LESS THAN THREE YEARS OF AGE
PEDIATRIC HEMATOLOGY AND ONCOLOGY
2008; 25 (8): 705-722
Idiopathic neutropenia (IN) in children is characterized by decreased neutrophil counts (<1500/microl), can be acute or chronic (greater than 6 months duration). The pathophysiology is not well understood; therefore, potential mechanisms of pediatric IN were investigated. An increase in Fas transcripts in neutrophils of IN patients compared to age-matched healthy control (HC) neutrophils was observed (p<0.005). Increased expression of Fas protein was found in IN neutrophils, while Fas surface expression on other immune cells was similar. Plasma from acute IN patients had higher protein levels of soluble FasL than chronic IN patients. When HC neutrophils were incubated in plasma from IN patients, greater rates of apoptosis were observed. Biochemical studies suggest the apoptotic factor(s) in plasma is heat-sensitive, non-IgG, and 12-50 kD protein. Addition of anti-sFasL blocking antibodies to patient plasma caused a statistically significant decrease in neutrophil apoptosis. These studies show that the Fas/FasL pathway could be associated with neutrophil apoptosis in childhood IN.
View details for DOI 10.1016/j.clim.2008.08.006
View details for PubMedID 18819843
Gene expression and pathway analysis of immune thrombocytopenic purpura
BRITISH JOURNAL OF HAEMATOLOGY
2008; 140 (1): 99-103
Allogeneic hematopoietic stem cell transplantation (HSCT) is a standard treatment for a variety of hematologic conditions. However, very young children may experience different complications of HSCT compared to older patients. The authors retrospectively analyzed the results of 51 transplants performed on children less than 3 years of age between June 1987 and October 2005. Donors were matched-related (n = 21), partially mismatched related (n = 3), and unrelated (n = 27). The majority of patients had one or more grade III organ toxicities, but all nonrelapse deaths were attributable to infection. Perineal dermatitis was found in a large number (73%) of recipients of cyclophosphamide-based conditioning regimens. The 1-year transplant-related mortality (TRM) was 14%, but significantly declined in the more modern period. Grades II-IV acute graft-versus-host-disease (GvHD) was seen in 22% of patients, while chronic extensive GvHD developed in only 7% of patients. Relapse was seen in 40% of transplants performed for a malignant condition, most commonly in those patients not in remission at time of HSCT. The 5-year event-free survival (EFS) and overall survival (OS) were 53 and 64%, respectively. Recipients of fractionated total body irradiation (fTBI) were more likely to have at least one long-term sequelae than patients who received chemotherapy-based regimens (p = .014). These data demonstrate that HSCT can be performed safely in very young children, especially as supportive-care techniques improve. Cyclophosphamide-related perineal dermatitis is a unique complication in very young children. Finally, the incidence of acute and chronic GvHD in this population is low.
View details for DOI 10.1080/08880010802243524
View details for PubMedID 19065437
Cold agglutinin syndrome in pediatric liver transplant recipients
2007; 11 (8): 931-936
A global expression profile of peripheral blood from patients with immune thrombocytopenic purpura (ITP) was performed that identified an ITP-specific signature, which also included interferon (IFN)-induced genes. Several genes correlated with ITP have been shown to be associated with expression signatures in systemic lupus erythematosis and rheumatoid arthritis, indicating an overlap with other autoimmune disorders. Pathway analysis demonstrated that IFN signalling, death receptor and protein ubiquitination pathways were associated with ITP. These results provide the first glimpse of the genes and pathways consistently aberrant in ITP, identifying new targets for investigations of pathogenesis and treatment of ITP.
View details for DOI 10.1111/j.1365-2141.2007.06881.x
View details for PubMedID 18005267
Anemia is a common finding in post-liver transplant patients. Causes for the anemia include nutritional deficiencies, red cell aplasia as well as immune-mediated hemolysis. One of the immunologic causes of hemolytic anemia is drug-induced hemolysis. Tacrolimus is a common immunosuppressant used in post-liver transplant patients to prevent graft rejection. There have been reports of tacrolimus-associated hemolytic anemia secondary to hemolytic uremic syndrome as well as autoimmune hemolysis. There are also case-reports of severe hemolytic anemia related to cold agglutinin production in post-liver transplant patients. We described in this paper three cases of severe cold agglutinin hemolytic anemia in three pediatric liver transplant patients. Steroid therapy, plasmapheresis and withdrawal of tacrolimus led to resolution of the severe hemolytic process in each case. Whether the immune-mediated hemolysis is related to tacrolimus is not clear and needs to be characterized further.
View details for DOI 10.1111/j.1399-3046.2007.00795.x
View details for PubMedID 17976131