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Total 198 results found since Jan 2013.
Activated protein C, protease activated receptor 1, and neuroprotection
Protein C is a plasma serine protease zymogen whose active form, activated protein C (APC), exerts potent anticoagulant activity. In addition to its antithrombotic role as a plasma protease, pharmacologic APC is a pleiotropic protease that activates diverse homeostatic cell signaling pathways via multiple receptors on many cells. Engineering of APC by site-directed mutagenesis provided a signaling selective APC mutant with 3 Lys residues replaced by 3 Ala residues, 3K3A-APC, that lacks >90% anticoagulant activity but retains normal cell signaling activities. This 3K3A-APC mutant exerts multiple potent neuroprotective ac...
Source: Blood - July 12, 2018 Category: Hematology Authors: Griffin, J. H., Zlokovic, B. V., Mosnier, L. O. Tags: Thrombosis and Hemostasis, Vascular Biology, Review Articles, Review Series Source Type: research
Rapid Decline in Kidney Function in Sickle Cell Disease
Conclusion:Rapid decline in eGFR is common in SCD. Use of ACE-I/ARB and history of stroke are associated with rapid decline in renal function. Rapid decline in eGFR is associated with an increased risk of death in SCD. Long-term studies are required to determine if therapies that may reduce loss of kidney function may decrease mortality in SCD.DisclosuresAtaga: Pfizer: Research Funding; Bioverativ: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals: Honoraria; Modus Therapeutics: Honoraria; Global Blood Therapeutics: Honoraria, Membership on an entity's Board of Directo...
Source: Blood - November 21, 2018 Category: Hematology Authors: Derebail, V. K., Ciccone, E. J., Zhou, Q., Cai, J., Ataga, K. I. Tags: 114. Hemoglobinopathies, Excluding Thalassemia-Clinical: Poster I Source Type: research
Relationship between Hemolytic Index Early in Life with Development of Abnormal Transcranial Doppler Velocities in Pediatric Patients with Sickle Cell Anemia
Conclusions: This retrospective study noted an increased risk for development of an abnormal or conditional TCD with an increased HI. The addition of hemoglobin to the HI to form HHI showed an elevated risk for abnormal or conditional TCD to the same degree as HI itself. These results could offer an additional tool in the evaluation of the pediatric SCA population, although these results would benefit from a prospective look. Further look into a possible association between HI and other SCD related complications such as stroke and acute chest syndrome could provide further information for the treating team for the overall ...
Source: Blood - November 21, 2018 Category: Hematology Authors: Goubeaux, D. L., Sherman, A., Kalpatthi, R., Woods, G. Tags: 114. Hemoglobinopathies, Excluding Thalassemia-Clinical: Poster II Source Type: research
Direct Oral Anticoagulants and Mortality in Atrial Fibrillation
ConclusionsIn this cohort of newly diagnosed NVAF patients treated in routine clinical practice, DOAC therapy was associated with a lower risk for death compared to no oral anticoagulation. Our findings provide further evidence for the importance of DOAC therapy in NVAF patients.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - November 21, 2018 Category: Hematology Authors: Ellis, M., Ruslan, S., Ariel, H., Greenberg-Dotan, S., Battat, E., Hamburger-Avnery, O., Greenberg, D., Ronen, A. Tags: 332. Antithrombotic Therapy 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
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
Real World Experience of Direct Oral Anticoagulants with Comparison of Safety Outcomes to the Warfarin Era of Venous Thromboembolism Treatment
Conclusion:This retrospective audit shows that our local safety outcomes are comparable to clinical trials. Low dose anticoagulation and high falls risk (a surrogate marker of frailty) were significant risk factors for both clinically significant bleeding and thrombotic stroke in the DOAC population. These patients are likely frailer with greater co-morbidities and have shared risk factors for bleeding and stroke, suggesting that for these high risk patients, low dose anticoagulation does not negate their risk of complications and careful prescribing and close monitoring remain essential.The sub-comparison between VTE pati...
Source: Blood - November 21, 2018 Category: Hematology Authors: Brook, R., Aswapanyawongse, N., Lim, H. Y., Ho, P. Tags: 331. Pathophysiology of Thrombosis: Poster II Source Type: research
Indications, Efficacy and Complications of Kcentra Use in Reversing Coagulopathy
ConclusionsKcentra was used in several off-label clinical settings, with comparable mortality among the coumadin, rivaroxaban and apixaban groups and no identifiable benefit in the setting of cirrhosis, DIC or antiplatelet medications, but with an increased incidence of deep vein thrombosis and stroke.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - November 21, 2018 Category: Hematology Authors: Sritharan, N., Triulzi, D. Tags: 401. Basic Science and Clinical Practice in Blood Transfusion: Poster III Source Type: research
Activated protein C {beta}-glycoform promotes enhanced noncanonical PAR1 proteolysis and superior resistance to ischemic injury
In this study, a recombinant APC variant (APCN329Q) mimicking the naturally occurring APC-β plasma glycoform was found to exhibit superior PAR1 proteolysis at a cleavage site that selectively mediates cytoprotective signaling. APCN329Q also enhanced integrin αMβ2-dependent PAR1 proteolysis to exert significantly improved antiinflammatory activity on macrophages compared with wild-type APC. Recent therapeutic applications of recombinant APC in ischemic stroke models have used APC variants with limited anticoagulant activity to negate potential bleeding side effects. Using a mouse model of ischemic stroke and...
Source: Blood - August 13, 2015 Category: Hematology Authors: Gleeson, E. M., Dichiara, M. G., Salicio, A., Quinn, L. M., Drakeford, C., Russell, S. E., Walsh, P. T., Orbe, J., Hermida, J., Smith, O. P., O'Donnell, J. S., Montes, R., Preston, R. J. S. Tags: Thrombosis and Hemostasis, Brief Reports Source Type: research
How I use anticoagulation in atrial fibrillation
Atrial fibrillation is the most common cardiac arrhythmia and conveys a significant risk of morbidity and mortality due to related stroke and systemic embolism. Oral anticoagulation (OAC) is the mainstay of thromboembolism prevention, and management of anticoagulation can be challenging. For patients without significant valvular disease, decisions around anticoagulation therapy are first based on the presence of additional stroke risk factors, as measured by the CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75, diabetes, prior stroke or transient ischemic attack, vascular disease, age 65–74, and sex c...
Source: Blood - December 21, 2016 Category: Hematology Authors: Steinberg, B. A. Tags: How I Treat, Free Research Articles, Thrombosis and Hemostasis Source Type: research
Mast Cells Contribute to Brain Microvascular Permeability in Sickle Cell Disease
We examined the ability of mast cells to stimulate P-selectin expression and BBB permeability via ER stress in a sickle microenvironment.We isolated MCs from HbAA-BERK and HbSS-BERK, control and sickle mice, respectively; incubated them in vitro and collected mast cell conditioned media (MCCM) from HbAA MCs and HbSS MCs. Normal mouse brain microvascular endothelial cells (mBMECs) were treated with unconditioned MCCM, HbAA MCCM, or HbSS MCCM to examine the effect of mast cell activation on endothelium. We observed increased mast cell activity in HbSS mice evinced by significantlyhigher plasma and skin histamine levels, comp...
Source: Blood - November 21, 2018 Category: Hematology Authors: Mittal, A. M., Tran, H., Sagi, V., Nguyen, A., Luk, K., Nguyen, J., Lei, J., Gupta, K. Tags: 113. Hemoglobinopathies, Excluding Thalassemia-Basic and Translational Science: Sickle Cell Disease-Role of Coagulation and Inflammation in Pathophysiology Source Type: research
NOAC Therapy Is Also Effective and Safe in Patients Older Than 80 Years -- Results of the Prospective Dresden NOAC Registry (NCT01588119)
Conclusions: During long-term FU of more than 2.5 years, this very old population of NOAC recipients demonstrated low rates of cardiovascular or major bleeding complications during active NOAC therapy. Approximately one quarter of the study population died during follow-up, with cardiovascular events being the leading cause of death. Only 11 fatal bleeding events were observed; however, most of the 58 fatal thromboembolic events occurred after anticoagulation was discontinued. This indicates that continued anticoagulation with NOACs may result in a beneficial risk-benefit ratio also in very old patients.DisclosuresBeyer-We...
Source: Blood - November 21, 2018 Category: Hematology Authors: Beyer-Westendorf, J., Tittl, L., Naue, C., Marten, S. Tags: 332. Antithrombotic Therapy: Management of Challenging Patients and Scenarios Source Type: research
Efficacy and Safety of Direct Oral Factor Xa Inhibitors in 795 Morbidly Obese Patients
Conclusions: Our study is the largest study examining morbidly obese patients on DOACS and provides further evidence of comparable efficacy and safety of the direct oral anti-Xa inhibitors, compared to warfarin, in morbidly obese patients with AF and VTE.DisclosuresKushnir: Janssen: Research Funding. Billett: Bayer: Consultancy; Janssen: Research Funding.
Source: Blood - November 21, 2018 Category: Hematology Authors: Kushnir, M., Choi, Y., Eisenberg, R., Rao, D., Tolu, S., Gao, J., Mowrey, W., Billett, H. H. Tags: 332. Antithrombotic Therapy: Management of Challenging Patients and Scenarios Source Type: research
