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Total 12 results found since Jan 2013.
Hydroxyurea reduces cerebral metabolic stress in patients with sickle cell anemia
Chronic transfusion therapy (CTT) prevents stroke in selected patients with sickle cell anemia (SCA). We have shown that CTT mitigates signatures of cerebral metabolic stress, reflected by elevated oxygen extraction fraction (OEF), which likely drives stroke risk reduction. The region of highest OEF falls within the border zone, where cerebral blood flow (CBF) nadirs; OEF in this region was reduced after CTT. The neuroprotective efficacy of hydroxyurea (HU) remains unclear. To test our hypothesis that patients receiving HU therapy have lower cerebral metabolic stress compared with patients not receiving disease-modifying t...
Source: Blood - May 29, 2019 Category: Hematology Authors: Fields, M. E., Guilliams, K. P., Ragan, D., Binkley, M. M., Mirro, A., Fellah, S., Hulbert, M. L., Blinder, M., Eldeniz, C., Vo, K., Shimony, J. S., Chen, Y., McKinstry, R. C., An, H., Lee, J.-M., Ford, A. L. Tags: Sickle Cell Disease, Red Cells, Iron, and Erythropoiesis Source Type: research
B0 Vs. Non-B0 Genotype: Differences in Non-Transfusion-Dependent Thalassemia Patients
Conclusions: Heart remodelling related to a high cardiac output state cardiomyopathy was more pronounced in patients with homozygous β°/β° genotype. Osteoporososis was significantly more frequent in patients with homozygous β°/β° genotype, treated for more than two-thirds with DFO therapy. These data support the knowledge of different phenotypic groups in the management of NTDT patients.TableDisclosuresPepe: Chiesi Farmaceutici S.p.A., ApoPharma Inc., and Bayer: Other: No profit support.
Source: Blood - November 21, 2018 Category: Hematology Authors: Pepe, A., Pistoia, L., Maddaloni, D., Grippo, T., Benni, M., Sardella, L., Sanna, M. G., Giugno, G., Guerrini, G., Maggio, A., Renne, S., Missere, M., Positano, V., Meloni, A. Tags: 112. Thalassemia and Globin Gene Regulation: Poster I Source Type: research
Cerebral Infarcts and Cerebrovascular Disease in Neurologically Intact Tanzanian Children with Sickle Cell Anaemia
Conclusions:The prevalence of SCI on MRI is high in children with SCA without neurological history living in Africa even when TCD CBFV is normal. Children and adolescents with all grades of vasculopathy on MRA are at higher risk of brain parenchymal injury. The lack of association between SCI and hemoglobin may be related to the relatively severe anemia in our African study. As MRA contrast depends on velocity of blood flowing in vessels, it is not surprising that Grade 1 turbulence on MRA appears to reflect high CBFV on TCD. Importantly, high TCD velocity and Grade 1 turbulence may reflect the potentially reversible early...
Source: Blood - November 21, 2018 Category: Hematology Authors: Mwakatika, M. M., Saunders, D. E., Makani, J., Kirkham, F. J. Tags: 114. Hemoglobinopathies, Excluding Thalassemia-Clinical: Poster I Source Type: research
Burden and Risk of Neurological and Cognitive Impairment in Pediatric Sickle Cell Anemia in Uganda (BRAIN SAFE): Final Results of the Cross-Sectional Analysis
Conclusions: These data demonstrate early, frequent neurovascular pathology for each outcome tested. Abnormal neurocognitive test results significantly increased with age or non-normal TCD. Our findings provide a baseline for longitudinal assessment and incentive for intervention. Enhanced research capacity was gained for junior faculty, trainees and staff, in areas of the conduct of brain research and focus on pediatric SCD, TCD performance and neuro-epidemiology.Funding: 1R21HD089791 (PIs: Idro, Green)DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - November 21, 2018 Category: Hematology Authors: Green, N. S., Munube, D., Bangirana, P., Opoka, R., Kayongo, E., Mupere, E., Buluma, L. R., Kebirungi, B., Sekibira, R., Kiguli, S., Kawooya, M., Lubowa, S. K., Elkind, M. S. V., Li, G., LaRussa, P., Idro, R. Tags: 114. Hemoglobinopathies, Excluding Thalassemia-Clinical: Poster II Source Type: research
Brain Magnetic Resonance Imaging and Angiography Findings in Ugandan Children with Sickle Cell Anemia; A Cross Sectional Study
ConclusionsBrain injury in Uganda children with SCA begins early in childhood and becomes a common finding during later childhood. Early screening for stroke and intervention therapy is warranted to prevent sickle brain vasculopathy initiated early after diagnosis. The risk factors for such early brain injury should be investigated.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - November 21, 2018 Category: Hematology Authors: Idro, R., Green, N. S., Munube, D., Buluma, L. R., Kebirungi, B., Opoka, R., Bangirana, P., Mupere, E., Kayongo, E., Sekibira, R., Kasirye, P., Lubowa, S. K., Kawooya, M., LaRussa, P., Minja, F. Tags: 114. Hemoglobinopathies, Excluding Thalassemia-Clinical: Poster II Source Type: research
Red cell exchange transfusions lower cerebral blood flow and oxygen extraction fraction in pediatric sickle cell anemia
Blood transfusions are the mainstay of stroke prevention in pediatric sickle cell anemia (SCA), but the physiology conferring this benefit is unclear. Cerebral blood flow (CBF) and oxygen extraction fraction (OEF) are elevated in SCA, likely compensating for reduced arterial oxygen content (CaO2). We hypothesized that exchange transfusions would decrease CBF and OEF by increasing CaO2, thereby relieving cerebral oxygen metabolic stress. Twenty-one children with SCA receiving chronic transfusion therapy (CTT) underwent magnetic resonance imaging before and after exchange transfusions. Arterial spin labeling and asymmetric s...
Source: Blood - March 1, 2018 Category: Hematology Authors: Guilliams, K. P., Fields, M. E., Ragan, D. K., Eldeniz, C., Binkley, M. M., Chen, Y., Comiskey, L. S., Doctor, A., Hulbert, M. L., Shimony, J. S., Vo, K. D., McKinstry, R. C., An, H., Lee, J.-M., Ford, A. L. Tags: Pediatric Hematology, Sickle Cell Disease, Transfusion Medicine, Free Research Articles, Red Cells, Iron, and Erythropoiesis Source Type: research
Thrombophilia risk is not increased in children after perinatal stroke
Perinatal stroke causes cerebral palsy and lifelong disability. Specific diseases are definable, but mechanisms are poorly understood. Evidence suggests possible associations between arterial perinatal stroke and prothrombotic disorders, but population-based, controlled, disease-specific studies are limited. Understanding thrombophilia in perinatal stroke informs pathogenesis models and clinical management. We conducted a population-based, prospective, case-control study to determine the association of specific perinatal stroke diseases with known thrombophilias. Children with idiopathic magnetic resonance imaging–cl...
Source: Blood - May 18, 2017 Category: Hematology Authors: Curtis, C., Mineyko, A., Massicotte, P., Leaker, M., Jiang, X. Y., Floer, A., Kirton, A. Tags: Pediatric Hematology, Free Research Articles, Thrombosis and Hemostasis, Vascular Biology, CME article Source Type: research
Chronic and acute anemia and extracranial internal carotid stenosis are risk factors for silent cerebral infarcts in sickle cell anemia
This study includes 189 stroke-free patients with SCA from the Créteil newborn cohort (1992-2010) followed longitudinally by magnetic resonance imaging/MRA, including cervical MRA at the last assessment. All patients with abnormal TCD and/or intracranial stenoses were placed on a transfusion program. Mean follow-up was 9.9 years (range, 2.2-19.9 years; 1844 patient-years). Annual rates of clinical events were calculated. The cumulative risk for SCI was 39.1% (95% confidence interval [CI], 23.5%-54.7%) by age 18 years, with no plateau. We confirm that baseline hemoglobin level lower than 7 g/dL before age 3 years is ...
Source: Blood - March 5, 2015 Category: Hematology Authors: Bernaudin, F., Verlhac, S., Arnaud, C., Kamdem, A., Vasile, M., Kasbi, F., Hau, I., Madhi, F., Fourmaux, C., Biscardi, S., Epaud, R., Pondarre, C. Tags: Sickle Cell Disease, Free Research Articles, Red Cells, Iron, and Erythropoiesis Source Type: research
Chronic acute anemia and extracranial internal carotid stenosis are risk factors for silent cerebral infarcts in sickle cell anemia
This study includes 189 stroke-free patients with SCA from the Créteil newborn cohort (1992-2010) followed longitudinally by magnetic resonance imaging/MRA, including cervical MRA at the last assessment. All patients with abnormal TCD and/or intracranial stenoses were placed on a transfusion program. Mean follow-up was 9.9 years (range, 2.2-19.9 years; 1844 patient-years). Annual rates of clinical events were calculated. The cumulative risk for SCI was 39.1% (95% confidence interval [CI], 23.5%-54.7%) by age 18 years, with no plateau. We confirm that baseline hemoglobin level lower than 7 g/dL before age 3 years is ...
Source: Blood - March 5, 2015 Category: Hematology Authors: Bernaudin, F., Verlhac, S., Arnaud, C., Kamdem, A., Vasile, M., Kasbi, F., Hau, I., Madhi, F., Fourmaux, C., Biscardi, S., Epaud, R., Pondarre, C. Tags: Sickle Cell Disease, Free Research Articles, Red Cells, Iron, and Erythropoiesis Source Type: research
Magnetic resonance imaging/angiography and transcranial Doppler velocities in sickle cell anemia: results from the SWiTCH trial
The Stroke With Transfusions Changing to Hydroxyurea (SWiTCH) trial compared standard (transfusions/chelation) to alternative (hydroxyurea/phlebotomy) treatment to prevent recurrent stroke and manage iron overload in children chronically transfused over 7 years before enrollment. Standardized brain magnetic resonance imaging/magnetic resonance angiography (MRA) and transcranial Doppler (TCD) exams were performed at entry and exit, with a central blinded review. A novel MRA vasculopathy grading scale demonstrated frequent severe baseline left/right vessel stenosis (53%/41% ≥Grade 4); 31% had no vessel stenosis on either ...
Source: Blood - August 7, 2014 Category: Hematology Authors: Helton, K. J., Adams, R. J., Kesler, K. L., Lockhart, A., Aygun, B., Driscoll, C., Heeney, M. M., Jackson, S. M., Krishnamurti, L., Miller, S. T., Sarnaik, S. A., Schultz, W. H., Ware, R. E., for the SWiTCH Investigators Tags: Pediatric Hematology, Sickle Cell Disease, Free Research Articles, Red Cells, Iron, and Erythropoiesis, Vascular Biology, Clinical Trials and Observations Source Type: research
Comparison of vascular growth factors in the murine brain reveals placenta growth factor as prime candidate for CNS revascularization
Vascular bypass procedures in the central nervous system (CNS) remain technically challenging, hindered by complications and often failing to prevent adverse outcome such as stroke. Thus, there is an unmet clinical need for a safe and effective CNS revascularization. Vascular endothelial growth factors (VEGFs) are promising candidates for revascularization; however, their effects appear to be tissue-specific and their potential in the CNS has not been fully explored. To test growth factors for angiogenesis in the CNS, we characterized the effects of endothelium-specific growth factors on the brain vasculature and parenchym...
Source: Blood - August 1, 2013 Category: Hematology Authors: Gaal, E. I., Tammela, T., Anisimov, A., Marbacher, S., Honkanen, P., Zarkada, G., Leppanen, V.-M., Tatlisumak, T., Hernesniemi, J., Niemela, M., Alitalo, K. Tags: Vascular Biology, Gene Therapy Source Type: research
Regulatory T cells are strong promoters of acute ischemic stroke in mice by inducing dysfunction of the cerebral microvasculature
We have recently identified T cells as important mediators of ischemic brain damage, but the contribution of the different T-cell subsets is unclear. Forkhead box P3 (FoxP3)–positive regulatory T cells (Tregs) are generally regarded as prototypic anti-inflammatory cells that maintain immune tolerance and counteract tissue damage in a variety of immune-mediated disorders. In the present study, we examined the role of Tregs after experimental brain ischemia/reperfusion injury. Selective depletion of Tregs in the DEREG mouse model dramatically reduced infarct size and improved neurologic function 24 hours after stroke a...
Source: Blood - January 24, 2013 Category: Hematology Authors: Kleinschnitz, C., Kraft, P., Dreykluft, A., Hagedorn, I., Gobel, K., Schuhmann, M. K., Langhauser, F., Helluy, X., Schwarz, T., Bittner, S., Mayer, C. T., Brede, M., Varallyay, C., Pham, M., Bendszus, M., Jakob, P., Magnus, T., Meuth, S. G., Iwakura, Y., Tags: Thrombosis and Hemostasis Source Type: research
