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Jeffery L Miller - One of the best experts on this subject based on the ideXlab platform.

  • Absolute Reticulocyte Count acts as a surrogate for fetal hemoglobin in infants and children with sickle cell anemia
    PLoS ONE, 2015
    Co-Authors: Emily Riehm Meier, Myrna Weissman, Colleen Byrnes, Y. Terry Lee, Jeffery L Miller
    Abstract:

    Hemoglobin switching is largely complete in humans by six months of age. Among infants with sickle cell anemia (HbSS, SCA), reticulocytosis begins early in life as fetal hemoglobin (HbF) is replaced by sickle hemoglobin (HbS). The objective of this study was to determine if absolute Reticulocyte Count (ARC) is related to HbF levels in a cohort of pediatric SCA patients. A convenience sample of 106 children with SCA between the ages of 1 month and 20 years who were not receiving hydroxyurea or monthly blood transfusions were enrolled in this observational study. Hematologic data, including ARC and HbF levels, were measured at steady state. F-cells were enumerated by flow cytometry. Initial studies compared infants with ARC greater than or equal to 200 K/muL (ARC > 200) based upon the previously reported utility of this threshold as a predictive marker for SCA severity. Mean HbF and Fcell levels were significantly lower in the ARC > 200 group when compared to the ARC < 200 group. Both HbF and F-cell percentages were negatively correlated to ARC in infants and in children between the ages of 1 and 9 years. However, the inverse relationship was lost after the age of 10 years. Overall, decreased expression and distribution of HbF during childhood SCA is well-correlated with increased Reticulocyte production and release into the peripheral blood. As such, these data further support the clinical use of Reticulocyte enumeration as a disease severity biomarker for childhood sickle cell anemia.

Marcos Borato Viana - One of the best experts on this subject based on the ideXlab platform.

  • Reticulocyte Count is the most important predictor of acute cerebral ischemia and high risk transcranial doppler in a newborn cohort of 395 children with sickle cell anemia
    Annals of Hematology, 2016
    Co-Authors: Andre Rolim Belisario, Rahyssa Rodrigues Sales, Nayara Evelin Toledo, Maristela Braga De Sousa Rodrigues Muniz, Cibele Vellosorodrigues, Celia Maria Silva, Marcos Borato Viana
    Abstract:

    Stroke is a severe clinical manifestation of sickle cell anemia (SCA). Despite the prognostic relevance of transcranial Doppler (TCD), more accurate tools to assess stroke risk in children with SCA are required. Here, we describe the effect of clinical, laboratory, and molecular features on the risk of stroke and high-risk TCD in children from the newborn cohort of Minas Gerais, Brazil. Outcomes studied were acute cerebral ischemia and high-risk TCD. Clinical and hematological data were retrieved from children’s records. Genetic markers, which were known for their association with stroke risk, were genotyped by polymerase chain reaction/restriction fragment length polymorphism and sequencing. The cumulative incidence of acute cerebral ischemia by the age of 8 years was 7.4 % and that of high-risk TCD by the age of 11.5 years was 14.2 %. The final multivariate model for acute cerebral ischemia risk included high white blood cell Count and Reticulocyte Count, acute chest syndrome rate, and the single nucleotide polymorphisms (SNPs) TEK rs489347 and TNF-α rs1800629. The model for high-risk TCD included high Reticulocyte Count and the SNPs TEK rs489347 and TGFBR3 rs284875. Children with risk factors should be considered for intensive risk monitoring and for intervention therapy.

  • high Reticulocyte Count is an independent risk factor for cerebrovascular disease in children with sickle cell anemia
    Pediatric Blood & Cancer, 2011
    Co-Authors: Celia Maria Silva, Poliana Giovani, Marcos Borato Viana
    Abstract:

    Background Transcranial Doppler ultrasonography (TCD) is an important way of detecting risk of ischemic stroke in children with sickle cell anemia. Procedure A random sample of 262 FS-hemoglobin children from a newborn screening inception cohort in Brazil (1998–2005) was followed up to May 2009. Pulsed TCD followed STOP protocol. Children with mean blood flow velocity <170 cm/sec in cerebral arteries were classified as low risk; between 170 and 184, low conditional risk; between 185 and 199, high conditional risk; and ≥200, high risk. Results Median age, 6.2 years (2–11.2 years); 147 female; 13 children (5%) had ischemic stroke prior to TCD; 186/249 (74.7%) were classified as low risk; 19 (7.6%) as low conditional; 7 (2.8%) as high conditional; and 8 (3.2%) as high risk; inadequate tests, 11.6%. The probability of ischemic stroke at 10 years was 8.3% (SEM 2.3%); of stroke or high-risk TCD 15.6% (3.5%). Children with stroke or altered TCD (conditional and high risk) were compared to children with normal examinations. They were younger (P = 0.03), with lower hemoglobin (P = 0.003), higher leukocytosis (P = 0.015), and higher reticulocytosis (P < 0.001). Episodes per year of acute chest syndrome were also higher in that group, but not significantly (P = 0.09). Reticulocytosis remained the only significant variable upon multivariate analysis (P = 0.004). Basilar and middle cerebral artery velocities were significantly correlated (R = 0.55; P < 0.001). Conclusions Probability of stroke was similar to international reports; of belonging to high-risk group, lower. High-Reticulocyte Count was the most important factor associated with cerebrovascular disease. Basilar artery velocity >130 cm/sec seems to be an indirect sign of an underlying cerebrovascular disease. Pediatr Blood Cancer. 2010;56:116–121. © 2010 Wiley-Liss, Inc.

Theodore E Warkentin - One of the best experts on this subject based on the ideXlab platform.

George M Hoffman - One of the best experts on this subject based on the ideXlab platform.

B Stephenson - One of the best experts on this subject based on the ideXlab platform.

  • Reticulocyte Count and hemoglobin concentration predict survival in candidates for liver transplantation
    Transplantation, 2014
    Co-Authors: Richard D Parker, Chris Corbett, Ian A Rowe, Diarmaid D Houlihan, Matthew J Armstrong, Tony Bruns, James Hodson, Philip A Reuken, Bridget Gunson, B Stephenson
    Abstract:

    BACKGROUND Prognostic scores are used to assess the likelihood of mortality in cirrhosis and the necessity of liver transplantation. These models are imperfect and refinement would allow more accurate prognostication and selection of patients for transplant. This study investigated association of red cell parameters and mortality in liver transplant candidates. METHODS Data from patients with cirrhosis assessed for transplantation from 2008 to 2010 at Queen Elizabeth Hospital Birmingham, UK were reviewed retrospectively. Kaplan-Meier analysis and Cox regression models were used to generate indices predicting mortality. Accuracy of existing and updated models was tested by calculation of c-statistics. Results were validated in a cohort of patients assessed for liver transplant in Jena, Germany. RESULTS Data were collected from 386 patients in the study cohort. Median follow-up was 15 months (0-45). During follow-up, 151 patients (39%) were transplanted, 138 (36%) died, and 97 (25%) survived without transplant. Abnormal Reticulocyte Count (P<0.001, c-statistic 0.623) and hemoglobin concentration (P<0.001, c-statistic 0.609) predicted mortality in Cox regression analysis. Abnormal Reticulocyte Count was also found to predict mortality in competing risk analysis. Refining the Model for End-Stage Liver Disease (MELD) to incorporate Reticulocyte Count and hemoglobin concentration (MELD-red) improved predictive power from 0.701 to 0.731 (c-statistics). This was confirmed in an independent validation cohort of 157 patients with c-statistics of 0.787 and 0.816, respectively, for MELD and MELD-red. CONCLUSIONS Abnormal red cell indices, in particular increased Reticulocyte Count and decreased hemoglobin concentration, are associated with increased risk of death in liver transplant candidates. Refining MELD to incorporate these indices improves prediction of mortality.

  • ptu 063 high Reticulocyte Count predicts mortality in patients awaiting liver transplantation
    Gut, 2012
    Co-Authors: Richard D Parker, M A Armstrong, Chris Corbett, Ian A Rowe, B Stephenson, Diarmaid D Houlihan, James Ferguson
    Abstract:

    Introduction The shortage of donor organs for liver transplantation (LT) makes it essential that organs are allocated to patients with greatest need. There has been increasing interest in haemoglobin as a predictor of LT outcomes. We investigated red cell parameters as predictors of survival after LT assessment. Methods Data on patients with end-stage liver disease assessed for LT between 2008 and 2010 at University Hospitals Birmingham, UK, were reviewed retrospectively. Kaplan–Meier and Cox regression analysis identified parameters predictive of death on the waiting list. To construct an updated UKELD model including high Reticulocyte Count (defined as >80), cases that had not received LT at 12 months were randomly divided into two groups (2:1 ratio) to for model building and testing. Accuracy of the existing and new and models was tested by calculation of c-statistics. Results Data were collected from 393 patients. Median age was 55 years (range 17–73), 60% were male. Median UKELD was 56 (44–76). Median follow-up was 18 (0–45) months. In total 144 (37%) underwent LT. Abnormal Reticulocyte Count, seen in 120 patients (31%), was greatest predictor of death without LT (HR 3.1; 95% CI 1.7 to 5.6), compared to haemoglobin (HR 2.5; 95% CI 1.3 to 4.5) and MCV (HR 0.6; 95% CI 0.3 to 1.2). Abnormal Reticulocyte Count remained a significant predictor of death after adjustment for age, gender and diagnosis (p80; yes=1, No=0]). This model had improved predictive accuracy with a c-statistic of 0.79. Conclusion High Reticulocyte Count is associated with increased risk of death in patients awaiting LT. Remodelling UKELD to include high Reticulocyte Count improved accuracy of predicting death on the LT waiting list. Competing interests None declared.