Robertson J.D.,Haematology Service
Journal of Thrombosis and Haemostasis | Year: 2015
Due to progressive advances in surgical techniques, immunosuppressive therapies, and supportive care, outcomes from both solid organ transplantation and hematopoietic stem cell transplantation continue to improve. Thrombosis remains a challenging management issue in this context, with implications for both graft survival and long-term quality of life. Unfortunately, there remains a general paucity of pediatric-specific data regarding thrombosis incidence, risk stratification, and the safety or efficacy of preventative strategies with which to guide treatment algorithms. This review summarizes the available evidence and rationale underlying the spectrum of current practices aimed at preventing thrombosis in the transplant recipient, with a particular focus on risk factors, pathophysiology, and described antithrombotic regimens. © 2015 International Society on Thrombosis and Haemostasis.
Martinez-Lopez J.,Serviao de Hematologia |
Crooke A.,Serviao de Hematologia |
Crooke A.,Complutense University of Madrid |
Grande S.,Serviao de Hematologia |
And 5 more authors.
International Journal of Laboratory Hematology | Year: 2010
This study aimed to compare the sensitivity and accuracy of two methods of quantitative real-time polymerase chain reaction (qrt- PCR), in order to determine haematopoietic chimerism (CH): single nucleotide polymorphisms using TaqMan(TM)probesand insertion/ deletion polymorphisms using Hybridization (Hyb) probes. A total of 106 samples from 20 patients who underwent allogenic stem cell transplantation (n = 14) or live-donor liver transplantation (n = 6) were studied. The mean level of chimerism was 8.37% for the TM method and 7.73% in the Hyb method, which was not significantly different (P = 0.69). The Pearson correlation coefficient between the two methods was r =0.91 (P < 0.001). The estimation of the regression line, using the Passing and Balbock method was Intercept A -0.0381 [95% confidence interval (CI) -0.1265 to 0.0296) and Slope B: 1.04609(95% CI 0.9349-1.161). Bland-Altman data showed that the standard deviations, which differed between the two methods (%Hyb-%TM), were 0.98 and -1.28. The accuracy and sensitivity of qrt-PCR chimerism is independent of the method used if the optimization is adequate and satisfies the criteria for adequate study. Realtime PCR, independent of the method adopted, is a very good tool for study levels of CH. © 2009 Blackwell Publishing Ltd.
Sheen C.R.,Molecular Pathology Laboratory |
McDonald M.A.,University of Otago |
George P.M.,Molecular Pathology Laboratory |
Smith M.P.,Haematology Service |
Morris C.M.,University of Otago
Blood Cells, Molecules, and Diseases | Year: 2011
The factor VIII intron 22 inversion is the most common cause of hemophilia A, accounting for approximately 40% of all severe cases of the disease. Southern hybridization and multiplex long distance PCR are the most commonly used techniques to detect the inversion in a diagnostic setting, although both have significant limitations. Here we describe our experience establishing a multicolor fluorescent in situ hybridization (FISH) based assay as an alternative to existing methods for genetic diagnosis of the inversion. Our assay was designed to apply three differentially labelled BAC DNA probes that when hybridized to interphase nuclei would exhibit signal patterns that are consistent with the normal or the inversion locus. When the FISH assay was applied to five normal and five inversion male samples, the correct genotype was assignable with p< 0.001 for all samples. When applied to carrier female samples the assay could not assign a genotype to all female samples, probably due to a lower proportion of informative nuclei in female samples caused by the added complexity of a second X chromosome. Despite this complication, these pilot findings show that the assay performs favourably compared to the commonly used methods. © 2010 Elsevier Inc.
Crespo C.,University of Barcelona |
Perez-Simon J.A.,University of Seville |
Rodriguez J.M.,EMEA Therakos Johnson and Johnson Company |
Sierra J.,Haematology Service |
Brosa M.,Oblikue Consulting
Clinical Therapeutics | Year: 2012
Background: Chronic graft-versus-host disease (cGvHD) is the leading cause of late nonrelapse mortality (transplant-related mortality) after hematopoietic stem cell transplant. Given that there are a wide range of treatment options for cGvHD, assessment of the associated costs and efficacy can help clinicians and health care providers allocate health care resources more efficiently. Objective: The purpose of this study was to assess the cost-effectiveness of extracorporeal photopheresis (ECP) compared with rituximab (Rmb) and with imatinib (Imt) in patients with cGvHD at 5 years from the perspective of the Spanish National Health System. Methods: The model assessed the incremental cost-effectiveness/utility ratio of ECP versus Rmb or Imt for 1000 hypothetical patients by using microsimulation cost-effectiveness techniques. Model probabilities were obtained from the literature. Treatment pathways and adverse events were evaluated taking clinical opinion and published reports into consideration. Local data on costs (2010 Euros) and health care resources utilization were validated by the clinical authors. Probabilistic sensitivity analyses were used to assess the robustness of the model. Results: The greater efficacy of ECP resulted in a gain of 0.011 to 0.024 quality-adjusted life-year in the first year and 0.062 to 0.094 at year 5 compared with Rmb or Imt. The results showed that the higher acquisition cost of ECP versus Imt was compensated for at 9 months by greater efficacy; this higher cost was partially compensated for (€517) by year 5 versus Rmb. After 9 months, ECP was dominant (cheaper and more effective) compared with Imt. The incremental cost-effectiveness ratio of ECP versus Rmb was €29,646 per life-year gained and €24,442 per quality-adjusted life-year gained at year 2.5. Probabilistic sensitivity analysis confirmed the results. The main study limitation was that to assess relative treatment effects, only small studies were available for indirect comparison. Conclusion: ECP as a third-line therapy for cGvHD is a more cost-effective strategy than Rmb or Imt. © 2012 Elsevier HS Journals, Inc.
Merono T.,University of Buenos Aires |
Rosso L.G.,University of Buenos Aires |
Sorroche P.,Central Laboratory |
Boero L.,University of Buenos Aires |
And 2 more authors.
European Journal of Clinical Investigation | Year: 2011
Introduction Iron overload (IO) is defined as an increase in storage iron, regardless of the presence or absence of tissue damage. Whether increased iron stores are involved in the pathogenesis of cardiovascular disease remains controversial. Objectives To study insulin resistance markers, lipoprotein profile, activities of anti and prooxidant enzymes and cholesteryl ester transfer protein (CETP) in patients with IO. Methods Twenty male patients with IO were compared with 20 sex- and age-matched controls. General biochemical parameters, lipoprotein profile, and activities of paraoxonase 1, employing two substrates, paraoxon (PON) and phenylacetate (ARE), lipoprotein-associated phospholipase A2 (Lp-PLA2) and CETP were determined. Results IO patients showed higher levels of HOMA-IR and triglycerides [median (Q1-Q3)] [128 (93-193) vs. 79(51-91)mgdL-1, P<0·0005] while lower high-density lipoprotein (HDL) cholesterol (mean±SD) (41±9 vs. 52±10mgdL-1, P<0·0005) in comparison with controls. Moreover, the triglycerides/HDL-cholesterol [3·2 (2·0-5·1) vs. 1·5 (1·0-1·9), P<0·0005] ratio and oxidized low-density lipoprotein levels [94 (64-103) vs. 68 (59-70)IUL-1, P<0·05] were increased in the patient group. Although no difference was observed in ARE activity, PON activity was decreased in IO patients [246 (127-410) vs. 428 (263-516) nmolmL-1min-1, P<0·05]. In addition, CETP and Lp-PLA2 activities were also increased in the patients (189±31 vs. 155 ± 36%ml-1h-1, P<0·005; and 10·1±2·9 vs. 8·2±2·4μmolmL-1h-1, P<0·05, respectively). Associations between ferritin concentration and the alterations in lipid metabolism were also found. Multiple regression analyses identified HOMA-IR as independent predictor of CETP activity (B=65·9, P<0·0001, r2=0·35), as well as ferritin concentration of Lp-PLA2 activity (B=3·7, P<0·0001, r2=0·40) after adjusting for confounding variables. Conclusions IO patients presented not only insulin resistance but also metabolic alterations that were related to elevated iron stores and are associated with high risk of cardiovascular disease. © 2010 The Authors. European Journal of Clinical Investigation © 2010 Stichting European Society for Clinical Investigation Journal Foundation.