Predictors of remission in children with newly diagnosed immune thrombocytopenia: Data from the Intercontinental Cooperative ITP Study Group Registry II participants

Immune thrombocytopenia (ITP) in childhood spontaneously remits in up to 80% of affected children. Predictors of remission are not well understood and identifying them could be useful for treatment decisions that impact outcomes.
Data from a large prospective cohort of pediatric patients with ITP (Registry II of Intercontinental Cooperative ITP Study Group [ICIS]) was analyzed to investigate factors that might predict remission. Included children were >4 months and 20 years of age with newly diagnosed ITP based on standard criteria. Therapy was classified as no systemic pharmacologic therapy, IVIG alone, corticosteroids alone, anti-D Ig alone, IVIG, and steroids in combination, and other.
1,239 patients were analyzed, 705 had follow-up data and came from 45 different institutions. Data collected through 12 months or through 12 and 24 months. More than half of the patients had no or mild bleeding. Patients were managed with observation alone (28%), IVIG alone (25%), corticosteroids alone (13%), and anti-D Ig (3%). Remission was achieved in 419/705 (59%) at 12 months and 211/383 (55%) at 24 months. Younger age (especially patients 1 year and 1 to 6 years) was associated with highest remission rates at both 12 and 24 months. Significant bleeding at diagnosis and pharmacologic treatment at diagnosis were statistically associated with remission at both 12 and 24 months. Highest remission rate at both 12 and 24 months occurred in the group treated with combination of corticosteroids and IVIG at diagnosis (76% and 77% respectively). Gender and platelet count at diagnosis were not significantly associated with ITP remission rates. Lower platelet count at diagnosis was not predictive of remission (contrary to previous reports).
Large numbers of patients were lost to follow-up, management decisions were at the discretion of the treating provider at multiple different institutions, and other lab studies that can impact disease course (such as ANA and red cell antibodies) were not collected.
Although this study found that combination treatment with IVIG and steroids may help prevent chronic disease, it would not be appropriate to recommend this upfront at this point.

Venous Thromboembolism in Pediatric Hematopoietic Cell Transplant: A Multicenter Cohort Study

This retrospective study examined the prevalence of venous thromboembolism (VTE) in pediatric patients undergoing a hematopoietic stem cell transplant. To date there has been no large retrospective study to examine both the prevalence and risk factors associated with VTE in this at-risk population.
Utilizing the pediatric health information system; a large database comprising information from 49 US pediatric tertiary care hospitals, ICD-9 codes were used to identify patients who underwent allogeneic or autologous stem cell transplant from January 2010 to September 2014. ICD-9 codes were used to identify VTE events, disease-specific indications for transplant and transplant complications including GVHD up to one-year post transplant.
4,158 eligible patients were identified that underwent a transplant. A total of 209 VTE events were identified, leading to a prevalence of 6.97%. 70% were DVTs, 13% Budd-Chiari syndrome, 9% Pulmonary embolism and 8% portal venous thrombosis. When divided between age groups, the highest prevalence was seen in those 1 month to 1-year-old (12.54%) and patients older than 21 years old (10.31%). Risk factors for VTE were identified as age >13yrs old (OR 1.38; 95%CI 1.08-1.77, p0.01) and allogeneic transplant (OR 1.60; 95%CI 1.19-2.15, p0.01). Finally, patients with VTE had increased length of stay in hospital (81 vs 54 days, p0.01), a median length of stay in the intensive care unit (18 vs 12 days, p0.01) and increased 1-year mortality (13.9% vs 5.9%, p0.01).
This is a retrospective study that depends on ICD-9 coding to correctly identify patients. Certain risk factors for VTE were not analyzed in the data including inherited thrombophilias, or prior history of VTE which would have been helpful information when analyzing the results.
The overall prevalence of VTE in patients undergoing hematopoietic stem cell was 6.97%, which is comparable to previous smaller pediatric studies. The identified age groups for VTE, and risk factors demonstrated by this study may increase awareness of this complication in the post-transplant period.

BSH Guideline: management of thrombotic and haemostatic issues in paediatric malignancy.

Very good guideline for the management of VTE and bleeding in pediatric malignancy.

Utility of the immature platelet fraction in pediatric immune thrombocytopenia: Differentiating from bone marrow failure and predicting bleeding risk

The immature platelet fraction (IPF) is an emerging laboratory test for measuring platelet production/turnover. It has been proposed that these immature platelets are more hemostatic and an increase in IPF more consistent with ITP, compared to BMF.
The two objectives were to examine the ability of IPF to help distinguish patients with BMF from ITP in their initial presentation of thrombocytopenia and to determine whether the IPF or AIPN could identify a subset of patients with ITP who were at increased risk of significant bleeding.
Retrospective chart review of thrombocytopenic patients, 2 months – 21 years old, with platelet counts 50 × 10e9/L at Children's Hospital of Philadelphia (CHOP) from November 1, 2013 to July 1, 2015. Charts reviewed for final diagnosis and bleeding symptoms. A bleeding severity score was retrospectively assigned.
272 patients were reviewed: 97 ITP, 11 BMF, 126 malignancy, 38 other. Cut-off IPF > 5.2% differentiated ITP from BMF with 93% sensitivity and 91% specificity. Absolute immature platelet number differed in all three bleeding severity groups (mild, moderate, severe). On multivariate analysis, an IPF 10.4% was confirmed as an independent predictor of bleeding risk at platelet counts 10 × 1e09/l in patients with ITP.
Single centre, retrospective, chart review (bleeding symptoms collected based on what was documented in chart), management of ITP not standardized (physician dependent if treatment provided or not thus potentially influencing bleeding symptoms), no blinding when assigning bleeding scores.
IPF measurement may have utility in diagnosis of ITP. In addition, IPF may be useful for prediction of relative future risk of bleeding in ITP patients, however there are limitations with the bleeding scores in this study.

Timing and severity of inhibitor development in recombinant versus plasma-derived factor VIII concentrates: a SIPPET analysis

Inhibitor development remains a significant problem in congenital hemophilia, with a multi-factorial etiology. The SIPPET trial demonstrated that the risk of inhibitors was nearly twice as high with recombinant products as compared to plasma-derived. While most inhibitors developed within the first 20 exposure days (ED), there is little data in the literature on the time course of inhibitor development.
SIPPET was a randomized trial comparing recombinant and plasma-derived (von Willebrand containing) factor replacement products for their risk of inhibitor development. This post-hoc analysis examined the results of frequent inhibitor testing done on the included patients. Inhibitors were assessed every 3-4 EDs for patients treating on demand and every 2 weeks for patients on prophylaxis, or as clinically indicated.
All inhibitors occurred within 39 ED and 90% within 20 ED (34 and 16 ED respectively for high-titre inhibitors). Inhibitors occurred earlier with recombinant products, peaked at a higher level, and persisted longer. In the first 5 EDs, the hazard ratio for recombinant products was 3.14 for all inhibitors and 4.19 for high-titre. Evaluation of the severity of the immunogenic effect also revealed an increasing hazard ratio for recombinant products with increasing Bethesda titres.
This is a post-hoc analysis of a relatively small sample pool. Because the comparison is between high-purity recombinant product and von Willebrand containing plasma derived product, the role of von Willebrand factor cannot be determined (which may be a relevant consideration in immunogenicity).
The difference in immunogenicity between recombinant and plasma-derived Factor VIII products is temporal, qualitative, and quantitative.