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Total 187 results found since Jan 2013.
Reduced ADAMTS13 activity during TTP remission is associated with stroke in TTP survivors
In conclusion, stroke is common after recovery from TTP and is associated with reduced ADAMTS13 activity during remission.
Source: Blood - September 26, 2019 Category: Hematology Authors: Upreti, H., Kasmani, J., Dane, K., Braunstein, E. M., Streiff, M. B., Shanbhag, S., Moliterno, A. R., Sperati, C. J., Gottesman, R. F., Brodsky, R. A., Kickler, T. S., Chaturvedi, S. Tags: Thrombosis and Hemostasis, Clinical Trials and Observations Source Type: research
Activated protein C ameliorates chronic graft-versus-host disease by PAR1-dependent biased cell signaling on T cells
Soluble thrombomodulin plasma concentrations are elevated in steroid-resistant graft-versus-host disease (GVHD), implying endothelial hypofunctioning for thrombomodulin-dependent generation of activated protein C’s (APC) anticoagulant, anti-inflammatory, and antiapoptotic functions. Recombinant thrombomodulin or APC administration decreases acute GVHD, manifested by intense inflammation and tissue destruction. Here, we administered recombinant murine wild-type (WT) APC to mice with established chronic GVHD (cGVHD), a less-inflammatory autoimmune-like disease. WT APC normalized bronchiolitis obliterans–induced p...
Source: Blood - August 29, 2019 Category: Hematology Authors: Sinha, R. K., Flynn, R., Zaiken, M., Paz, K., Gavin, A. L., Nemazee, D., Fernandez, J. A., Xu, X., Griffin, J. H., Blazar, B. R. Tags: Transplantation, Brief Reports Source Type: research
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 30, 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
How I manage anticoagulant therapy in older individuals with atrial fibrillation or venous thromboembolism
Anticoagulant therapy is the most effective strategy to prevent arterial and venous thromboembolism, but treating older individuals is challenging, because increasing age, comorbidities, and polypharmacy increase the risk of both thrombosis and bleeding. Warfarin and non–vitamin K antagonist oral anticoagulants are underused and often underdosed in the prevention of stroke in older patients with atrial fibrillation because of concerns about the risk of bleeding. Poor adherence to anticoagulant therapy is also an issue for older patients with atrial fibrillation and those at risk of recurrent pulmonary embolism. In th...
Source: Blood - May 23, 2019 Category: Hematology Authors: Chan, N. C., Eikelboom, J. W. Tags: How I Treat, Free Research Articles, Thrombosis and Hemostasis Source Type: research
Characterization and treatment of congenital thrombotic thrombocytopenic purpura
In conclusion, prespacer mutations are associated with earlier development of cTTP symptoms. Prophylactic ADAMTS13 replacement decreases the risk of end-organ damage such as ischemic stroke and resolved previously unrecognized symptoms in patients with nonovert disease.
Source: Blood - April 11, 2019 Category: Hematology Authors: Alwan, F., Vendramin, C., Liesner, R., Clark, A., Lester, W., Dutt, T., Thomas, W., Gooding, R., Biss, T., Watson, H. G., Cooper, N., Rayment, R., Cranfield, T., van Veen, J. J., Hill, Q. A., Davis, S., Motwani, J., Bhatnagar, N., Priddee, N., David, M., Tags: Thrombocytopenia, Platelets and Thrombopoiesis, Clinical Trials and Observations Source Type: research
A genome-wide association study identifies new loci for factor VII and implicates factor VII in ischemic stroke etiology
Factor VII (FVII) is an important component of the coagulation cascade. Few genetic loci regulating FVII activity and/or levels have been discovered to date. We conducted a meta-analysis of 9 genome-wide association studies of plasma FVII levels (7 FVII activity and 2 FVII antigen) among 27 495 participants of European and African ancestry. Each study performed ancestry-specific association analyses. Inverse variance weighted meta-analysis was performed within each ancestry group and then combined for a trans-ancestry meta-analysis. Our primary analysis included the 7 studies that measured FVII activity, and a secondary an...
Source: Blood - February 28, 2019 Category: Hematology Authors: de Vries, P. S., Sabater-Lleal, M., Huffman, J. E., Marten, J., Song, C., Pankratz, N., Bartz, T. M., de Haan, H. G., Delgado, G. E., Eicher, J. D., Martinez-Perez, A., Ward-Caviness, C. K., Brody, J. A., Chen, M.-H., de Maat, M. P. M., Franberg, M., Gill Tags: Thrombosis and Hemostasis Source Type: research
Arterial thromboembolic events preceding the diagnosis of cancer in older persons
In conclusion, the risk of arterial thromboembolic events begins to increase 150 days before the date of cancer diagnosis in older persons and peaks in the 30 days before.
Source: Blood - February 21, 2019 Category: Hematology Authors: Navi, B. B., Reiner, A. S., Kamel, H., Iadecola, C., Okin, P. M., Tagawa, S. T., Panageas, K. S., DeAngelis, L. M. Tags: Plenary Papers, Free Research Articles, Thrombosis and Hemostasis, Clinical Trials and Observations Source Type: research
The Incidence of Thromboembolism for Lenalidomide Versus Thalidomide in Older Patients with Newly Diagnosed Multiple Myeloma
Conclusion: In this propensity score weighted study of older patients with newly diagnosed MM, the cumulative incidences of VTE and ATE were similarly high in both lenalidomide- and thalidomide-treatment groups. The lack of difference in overall survival should be interpreted with caution as residual confounding such as severity of disease could influence this outcome. Our results suggest that appropriate risk stratification and vigilant thromboprophylaxis remain essential for MM patients receiving all types of immunomodulatory drugs.DisclosuresGarcia: Retham Technologies LLC: Consultancy; Shingoi: Consultancy; Portola: Re...
Source: Blood - November 21, 2018 Category: Hematology Authors: Li, A., Wu, Q. V., Warnick, G., Libby, E. N., Garcia, D. A., Lyman, G. H. Tags: 901. Health Services Research-Non-Malignant Conditions: Thrombosis and Anticoagulation Source Type: research
Burden of Hospital Readmissions for Venous Thromboembolism Among Patients with Cancer
Conclusions: In this real-world study, many patients hospitalized for cancer experienced a VTE event requiring re-hospitalization, which was the highest proportion of readmitted patients among acute medical illnesses analyzed in this study, with almost 30% readmitted within 30 days of post-discharge. Total costs of readmissions were substantial, as high as $41K for resubmissions due to primary diagnosis of DVT/PE. Improvement in VTE prophylaxis for patients with cancer may reduce the risk and frequency of VTE, and thus hospital readmissions, reducing the clinical and economic burden of VTE in this patient population.Sponso...
Source: Blood - November 21, 2018 Category: Hematology Authors: Amin, A. J., Deitelzweig, S., Lin, J., Lingohr-Smith, M., Menges, B., Neuman, W. R. Tags: 901. Health Services Research-Non-Malignant Conditions: Thrombosis and Anticoagulation Source Type: research
Practice Patterns in the Use of MRI/MRA and Chronic Transfusion Therapy for Monitoring and Treatment of Stroke in Pediatric Patients with Sickle Cell Anemia
Conclusions: The results of the DISPLACE practice patterns survey suggested nearly universal adoption of CRCT for children with abnormal TCD and prior overt stroke across sites. The use of MRI/MRA in detecting potential cerebrovascular abnormalities in the absence of clinical neurologic symptoms and for monitoring patients on CRCT was much more variable, which likely reflects the minimal amount of guidance for the use of MRI/MRA in SCA. Notably, a number of sites were using MRI/MRA to screen pediatric patients for cerebrovascular abnormalities and to monitor patients on CRCT. The variability in responses for MRI/MRA highli...
Source: Blood - November 21, 2018 Category: Hematology Authors: Schlenz, A. M., Mueller, M., Phillips, S., Melvin, C., Adams, R. J., Kanter, J. Tags: 901. Health Services Research-Non-Malignant Conditions: Poster III Source Type: research
Genotype-Phenotype Correlation in Congenital TTP: New Insights from a Multicentre Study with 121 Patients
Conclusion: At present, the Hereditary TTP Registry is the largest cohort on cTTP, to our knowledge. The large number of different mutations as well as confounding factors, including multi-ethnic and geographical factors in our internationally compiled patient cohort make unravelling the genotype-phenotype correlation in cTTP challenging. Yet, for c.4143_4144dupA, we can conclude that homozygous patients with ADAMTS13 c.4143_4144dupA are clinically less severely affected than compound heterozygotes due to the later onset of the disease in homozygotes, whereas the clinical characteristics are similar between compound hetero...
Source: Blood - November 21, 2018 Category: Hematology Authors: Van Dorland, A. A., Mansouri Taleghani, M., Friedman, K. D., George, J., Hrachovinova, I., Knobl, P., Lammle, B., Matsumoto, M., von Krogh, A. S., Schneppenheim, R., Aebi-Huber, I., Lukas, B., Cermakova, Z., Quist-Paulsen, P., Terrell, D., Vesely, S. K., Tags: 311. Disorders of Platelet Number or Function: Advances in the Treatment of TTP and HIT Source Type: research
Stroke in a Pediatric Immune Thrombocytopenia Case
Conclusion: Stroke in the immune thrombocytopenic clinic is a rare but hard to manage condition. Although its mechanism not understand well, the clinician should be identify and manage it carefully.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - November 21, 2018 Category: Hematology Authors: Leblebisatan, G., Cil, M., Sasmaz, H. I., Kilinc, Y., Soyupak, S. Tags: 311. Disorders of Platelet Number or Function Source Type: research
Vascular Proteomics Reveals Critical Roles of ADAMTS18 in Stroke Associated with Imbalanced Level of Von Willebrand Factor Versus ADAMTS13
Conclusion and Significance-Results of this first vascular proteomic study of Adamts18 KO mice establish a substantial new resource for investigation of how ADAMTS gene affects cellular phenotypes of stroke. These new findings contribute to inform novel prevention strategies and direct therapeutic development for stroke.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - November 21, 2018 Category: Hematology Authors: Zhu, R., Pan, Y.-H., Lu, T., Dang, S., Liao, C.-C., Zhang, W. Tags: 301. Vascular Wall Biology, Endothelial Progenitor Cells, and Platelet Adhesion, Activation, and Biochemistry: Poster III 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
Double Blind Randomized Control Trial of Postoperative Low Molecular Weight Heparin Bridging Therapy for Patients Who Are at High Risk for Arterial Thromboembolism (PERIOP 2)
ConclusionsIn patients with atrial fibrillation and/or mechanical heart valves who had warfarin interrupted for a procedure there was no benefit from post-procedure LMWH bridging.DisclosuresKovacs: Bayer: Research Funding; Daiichi Sankyo Pharma Development: Research Funding. Wells: Janssen: Honoraria; Sanofi: Honoraria; BMS: Honoraria, Research Funding; Bayer: Honoraria. Schulman: Boehringer-Ingelheim: Honoraria, Research Funding; Daiichi-Sankyo: Honoraria; Sanofi: Honoraria; Bayer: Honoraria.
Source: Blood - November 21, 2018 Category: Hematology Authors: Kovacs, M. J., Rodger, M., Wells, P. S., Bates, S. M., Kearon, C., Blostein, M., Lazo-Langner, A., Kahn, S., Schulman, S., Sabri, E., Solymoss, S., Ramsay, T., Pallaveshi, L., Anderson, D. Tags: 332. Antithrombotic Therapy: Management of Challenging Patients and Scenarios Source Type: research
A Nationwide Analysis of Outcomes of Stroke in Hospitalized Patients with Essential Thrombocythemia: 2006 to 2014
Conclusions:Patients with ET who are hospitalized with stroke have significantly worse outcomes. This study demonstrated that a statistically significant difference exists among different age groups of patients with ET and stoke who died during hospitalization when stratification is made using age groups and Charlson Score. This study may serve as an initial point to include new risk factors for further risk stratification. Early identification of patients at higher risk may reduce the incidence and decrease the morbidity of stroke in patients with ET.DisclosuresKota: BMS: Honoraria; Novartis: Honoraria; Xcenda: Honoraria;...
Source: Blood - November 21, 2018 Category: Hematology Authors: Ajebo, G., Badin, K., Forehand, W., Guddati, A. K., Kota, V. Tags: 634. Myeloproliferative Syndromes: Clinical: Poster III Source Type: research
Outcome of 472 Chronic Myeloid Leukemia Patients Treated with Frontline Nilotinib: A Gimema CML WP Analysis
CONCLUSION: Nilotinib as first-line treatment of newly diagnosed CP CML pts showed high rates of deep molecular responses, few progressions to AP/BP, and a high OS. Deep molecular response were similar in all age groups; as expected, ATEs were more frequent in pts > 60 y. These data suggest that: in pts > 60 y, the high efficacy of nilotinib should be weighed against its potential toxicity; in pts < 60 years, nilotinib may be a very good choice, with high efficacy and low toxicity.DisclosuresGugliotta: Novartis: Honoraria; Pfizer: Honoraria; Incyte: Honoraria; Bristol-Myers Squibb: Honoraria. Castagnetti: Bristol ...
Source: Blood - November 21, 2018 Category: Hematology Authors: Gugliotta, G., Castagnetti, F., Breccia, M., Iurlo, A., D'Adda, M., Stagno, F., Levato, L., Martino, B., Lunghi, F., Tiribelli, M., Rege Cambrin, G., Abruzzese, E., Rupoli, S., Gozzini, A., Pregno, P., Salvucci, M., Trabacchi, E., Caocci, G., Scortechini, Tags: 632. Chronic Myeloid Leukemia: Therapy: First Line Trials and Prognostic Factors of Treatment-Free Remission Source Type: research
Rivaroxaban Thromboprophylaxis in High-Risk Ambulatory Cancer Patients Receiving Systemic Therapy: Results of a Randomized Clinical Trial (CASSINI)
Conclusions: Rivaroxaban significantly reduced VTE and VTE-related death during the on-treatment period but not during the full study period; over one-third of events occurred post discontinuation of study drug. The incidence of major bleeding was low. The Khorana risk score cut-off of ≥2 identified cancer patients at high risk of thrombotic events both at baseline (4.53%) and during study (8.79% with additional 1.66% arterial events in placebo group). These results should inform future recommendations regarding thromboprophylaxis in at-risk ambulatory cancer patients.(Funded by Janssen; ClinicalTrials.gov number, NCT02...
Source: Blood - November 21, 2018 Category: Hematology Authors: Khorana, A. A., Soff, G. A., Kakkar, A. K., Vadhan-Raj, S., Riess, H., Wun, T., Streiff, M. B., Garcia, D. A., Liebman, H. A., Belani, C., O'Reilly, E. M., Patel, J. N., Yimer, H. A., Wildgoose, P., Burton, P., Vijapurkar, U., Kaul, S., Eikelboom, J., McB Tags: Late-Breaking Abstracts Session Source Type: research
Inherited Thrombophilia and the Risk of Arterial Ischemic Stroke: A Systematic Review and Meta-Analysis
Conclusions: Our results suggest that inherited thrombophilias including FVL, PTM, PCD, and PSD are associated with an increased risk of arterial ischemic stroke, particularly in young patients. The association with FVL and PTM is stronger in the homozygous than in the heterozygous state, suggesting a potential dose-response relationship and causal role for inherited thrombophilias. The implications of these findings with respect to the evaluation and management of patients with ischemic stroke require further investigation.DisclosuresCrowther: Alnylam: Equity Ownership; Daiichi Sankyo: Membership on an entity's Board of D...
Source: Blood - November 21, 2018 Category: Hematology Authors: Chiasakul, T., De Jesus, E., Tong, J., Chen, Y., Crowther, M., Garcia, D. A., Chai-Adisaksopha, C., Messe, S. R., Cuker, A. Tags: 331. Pathophysiology of Thrombosis: Poster II Source Type: research
Recurrent Stroke: The Role of Thrombophilia in a Large International Pediatric Stroke Population
CONCLUSIONS:Identifying children at increased for recurrent AIS events is important in intensifying preventative measures. Among 894 Canadian, English and German pediatric stroke patients, 17.9% experienced recurrent AIS at a median of 3.1 months after the index stroke. The presence of more than one prothrombotic risk factor is associated with AIS recurrence in childrenDisclosuresNo relevant conflicts of interest to declare.
Source: Blood - November 21, 2018 Category: Hematology Authors: Deveber, G., Kirkham, F. J., Shannon, K., Brandao, L. R., Strater, R., Kenet, G., Clausnizer, H., Moharir, M., Kausch, M., Askalan, R., MacGregor, D., Stoll, M., Torge, A., Dlamini, N., Ganesan, V., Prengler, M., Singh, J., Nowak Goettl, U. Tags: 331. Pathophysiology of Thrombosis: Poster III Source Type: research
Clinical, Laboratory, and Genetic Risk Factors for Thrombosis in Sickle Cell Disease
In conclusion, thrombotic events are common, occurring in 18% of SCD patients over a 10-year follow-up period. HbSS/Sβ0-thalassemia, frequent hospitalizations, kidney disease, and higher systolic blood pressures and AST concentrations were risk factors for thrombosis. Genome-wide marker array analysis points to a potential role of thrombomodulin in SCD-related thrombotic events based on replicated risk variants in THBD. Future studies integrating clinical, laboratory and genetic risk factors may improve our understanding for thrombosis and guide intervention practices in SCD.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - November 21, 2018 Category: Hematology Authors: Srisuwananukorn, A., Raslan, R., Zhang, X., Shah, B. N., Han, J., Gowhari, M., Jain, S., Molokie, R. E., Gordeuk, V. R., Saraf, S. L. Tags: 114. Hemoglobinopathies, Excluding Thalassemia-Clinical: Organ Damage and Clinical Complications in Sickle Cell Disease Source Type: research
Incidence of Bleeding in Patients with Sickle Cell Disease: A Population Based Study
Conclusion:The findings from our study indicate that SCD patients have a high cumulative incidence of bleeding. While the increased incidence of intracranial, urological, and retinal bleeding has been previously described and are confirmed here, we present the novel finding that SCD patients also have a high incidence of GI bleeding, the majority of which are from an upper GI source. The association of hemorrhagic stroke with a history of ischemic stroke is also confirmed. The association of bleeding with VTE is likely due, at least in part, to anticoagulation. Further studies on the causes and risk factors for GI bleeding...
Source: Blood - November 21, 2018 Category: Hematology Authors: Hariharan, N., Brunson, A. M., Keegan, T. H. M., Wun, T. Tags: 114. Hemoglobinopathies, Excluding Thalassemia-Clinical: Organ Damage and Clinical Complications in Sickle Cell Disease Source Type: research
Reduced Cerebral Metabolic Rate of Oxygen in Adults with Sickle Cell Disease
Conclusion:We observed reduced CMRO2 in patients with SCD compared to healthy controls due to low OEF. A reduced CMRO2 could pose a risk for ischemia, despite high flow rate delivering oxygen, because of low OEF. This is supported by the fact that the silent cerebral infarcts are located in regions with the lowest CMRO2. We postulate that patients with SCD have a reduced capacity to increase the OEF in regions with inadequate CBF resulting in local ischemia and local infarction. The pathogenesis of the reduced OEF remains unclear but could be related to arteriovenous shunting whereby there is insufficient time for oxygen t...
Source: Blood - November 21, 2018 Category: Hematology Authors: Vaclavu, L., Petersen, E. T., VanBavel, E. T., Majoie, C. B., Nederveen, A. J., Biemond, B. J. Tags: 114. Hemoglobinopathies, Excluding Thalassemia-Clinical: Organ Damage and Clinical Complications in Sickle Cell Disease Source Type: research
Low Hemoglobin Increases Risk for Stroke, Kidney Disease, Elevated Estimated Pulmonary Artery Systolic Pressure, and Premature Death in Sickle Cell Disease: A Systematic Literature Review and Meta-Analysis
Conclusions: In conclusion, comprehensive evaluation of peer-reviewed literature published over the past 20 years demonstrates a significant relationship between chronic anemia and worse clinical outcomes in individuals with SCD. Meta-analyses further demonstrate that even relatively modest differences in hemoglobin are important and support hemoglobin increase by ≥1 g/dL as a relevant therapeutic target. These results suggest that interventions that reduce hemolytic anemia may confer clinical benefit in this patient population.DisclosuresAtaga: Novartis: Consultancy, Honoraria; Bioverativ: Honoraria, Membership on an e...
Source: Blood - November 21, 2018 Category: Hematology Authors: Ataga, K. I., Gordeuk, V. R., Allen, I. E., Colby, J., Gittings, K., Agodoa, I. Tags: 114. Hemoglobinopathies, Excluding Thalassemia-Clinical: Organ Damage and Clinical Complications in Sickle Cell Disease Source Type: research
Clinical Relevance of Clonal Hematopoiesis in the Oldest-Old Population: Analysis of the "Health and Anemia" Study
Conclusion. Clonal hematopoiesis was associated with reduced survival in an oldest-old population. Specific mutational profiles define different risks of developing MDS and inflammatory/vascular diseases. Non mutational factors, such as early changes in red blood cell indices, may improve the capability to identify patients at increased risk of developing myeloid cancers.DisclosuresMeggendorfer: MLL Munich Leukemia Laboratory: Employment. Bolli: Celgene: Honoraria. Vassiliou: KYMAB: Consultancy, Equity Ownership; Celgene: Research Funding. Kern: MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach: MLL M...
Source: Blood - November 21, 2018 Category: Hematology Authors: Rossi, M., Meggendorfer, M., Zampini, M., Tettamanti, M., Riva, E., Saba, E., Manes, N., Milanesi, C., Marta, U., Morabito, L., Travaglino, E., Peano, C., Giulia, S., Asselta, R., Duga, S., Malik, K., Selmi, C., Civilini, E., Mandelli, S., Bolli, N., Vass Tags: 503. Clonal Hematopoiesis: Aging and Inflammation: Cause and consequence of clonal hematopoiesis Source Type: research
Determination of the Structural Changes Accompanying Binding of Protein S to Factor IXa
Conclusion: Based on our preliminary data, we conclude that PS binds strongly with FIXa, and the complex is stabilized by a shift in α-helical content as shown in Figure 1.Figure.1 shows the CD spectral change of PS (curve 1, right panel) due to addition of different concentration of FIXa (curve 2-8, right panel).DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - November 21, 2018 Category: Hematology Authors: Chatterjee, S., Guidry, J. J., Plautz, W. E., Watt, T., Majumder, R. Tags: 321. Blood Coagulation and Fibrinolytic Factors: Structural Biology of Coagulation Proteins Source Type: research
Results from Part A of the Hemoglobin Oxygen Affinity Modulation to Inhibit HbS Polymerization (HOPE) Trial (GBT440-031), a Placebo-Controlled Randomized Study Evaluating Voxelotor (GBT440) in Adults and Adolescents with Sickle Cell Disease
Conclusions: Data from Part A of the HOPE study demonstrate that treatment with voxelotor resulted in a dose-dependent increase in Hb with a large proportion of patients achieving Hb >1 g/dL improvement from baseline compared with placebo at 12 weeks. In addition, there was a dose-dependent decrease in hemolysis markers. Voxelotor was generally well tolerated at both doses. Hemolytic anemia of SCD has severe and life-threatening consequences and presents an unmet medical need. Voxelotor has potential to ameliorate complications of anemia associated with SCD.DisclosuresVichinsky: bluebird bio: Membership on an entity's B...
Source: Blood - November 21, 2018 Category: Hematology Authors: Vichinsky, E., Hoppe, C., Howard, J., Ataga, K. I., Nduba, V., El-Beshlawy, A., Diuguid, D. L., Al-Kindi, S., Brown, C., Hassab, H., Telfer, P., Tsitsikas, D. A., Unal, S., Kanter, J., Abboud, M. R., Gordeuk, V. R., Lehrer-Graiwer, J., Sherman, C., Tonda, Tags: 114. Hemoglobinopathies, Excluding Thalassemia-Clinical: Novel or Improved Approaches To Treating Sickle Cell Disease Source Type: research
Probability of TCD-Normalization in the "Drepagreffe" Trial Comparing Transplantation to Chronic Transfusion in Sickle Cell Anemia Children with Abnormal-Transcranial Doppler Is Associated with Lower Ang-2 and BDNF Plasma Levels
This study confirms the association between high levels of BDNF and high velocities, and suggests that transplantation increases the likelihood of TCD-normalization compared to transfusion, and is associated with reduced Ang-2 expression in plasma, which may reflect improved brain oxygenation.DisclosuresThuret: Addmedica: Research Funding; bluebird bio: Research Funding; Novartis: Research Funding. Pondarré: Addmedica: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Blue Bird Bio: Honoraria. Bernaudin: AddMedica: Honoraria; Pierre fabre: Research Funding; Cordons de Vie: Res...
Source: Blood - November 21, 2018 Category: Hematology Authors: Bernaudin, M., Khelif, Y., Chadebech, P., Bodivit, G., Jouard, A., Verlhac, S., Paillard, C., Thuret, I., Guitton, C., Runel, C., Missud, F., Arnaud, C., Kamdem, A., Pondarre, C., Pirenne, F., Bernaudin, F. Tags: 114. Hemoglobinopathies, Excluding Thalassemia-Clinical: Novel or Improved Approaches To Treating Sickle Cell Disease Source Type: research
Clinical and Laboratory Benefits of Early Initiation of Hydroxyurea with Pharmacokinetic Guided Dosing for Young Children with Sickle Cell Anemia
Conclusions: Hydroxyurea initiation at an early age using PK-guided dosing provides significant clinical benefits for young children with sickle cell anemia. These TREAT study data suggest that initiating hydroxyurea around one year of life using a personalized dosing strategy can provide better clinical and laboratory benefits than starting at the conventional 20 mg/kg/day weight-based dose. Very high HbF levels are observed at modest and well-tolerated doses of hydroxyurea, perhaps because treatment was initiated before the process of HbF inactivation is complete. Continued long-term follow-up of these patients will dete...
Source: Blood - November 21, 2018 Category: Hematology Authors: McGann, P. T., Niss, O., Dong, M., Marahatta, A., Mizuno, T., Kalinyak, K., Kalfa, T. A., Malik, P., Quinn, C. T., Ware, R. E., Vinks, A. A. Tags: 114. Hemoglobinopathies, Excluding Thalassemia-Clinical: Novel or Improved Approaches To Treating Sickle Cell Disease Source Type: research
Parenteral L-Arginine Improves Mitochondrial Function in Children with Sickle Cell Disease Admitted for Vaso-Occlusive Pain Episodes
Conclusion: These data demonstrate for the first time that Arg supplementation increases mitochondrial activity and decreases oxidative stress in children with SCD and VOE. Our prior study showed that complex V inhibition leads to increased mitochondrial oxidant production in platelets from SCD patients. The improvement in complex V function & decreased oxidative markers observed with Arg treatment are consistent with Arg-induced decrease in mitochondrial oxidant generation. However, Arg treatment potentially regulates other oxidant sources and could decrease overall oxidative stress in SCD patients. Arg therapy has be...
Source: Blood - November 21, 2018 Category: Hematology Authors: Shiva, S., Brown, L. A., Wang, Y., Dampier, C., Watt, A., Tripathi, V., Bhutta, A., Kumari, P., Figueroa, J., Zmitrovich, A., Morris, C. R. Tags: 114. Hemoglobinopathies, Excluding Thalassemia Clinical: Novel or Improved Approaches To Treating Sickle Cell Disease Source Type: research
High Molecular Weight Kininogen Contributes to End-Organ Damage and Mortality in a Mouse Model of Sickle Cell Disease
Conclusions: These data indicate that HK deficiency attenuates chronic inflammation, kidney failure, and heart hypertrophy, and improves survival of sickle cell mice.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - November 21, 2018 Category: Hematology Authors: Sparkenbaugh, E., Wilson, K., Kasztan, M., Pollock, D. M., McCrae, K. R., Pawlinski, R. Tags: 113. Hemoglobinopathies, Excluding Thalassemia-Basic and Translational Science: Sickle Cell Disease-Role of Coagulation and Inflammation in Pathophysiology 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
Asciminib, a Specific Allosteric BCR-ABL1 Inhibitor, in Patients with Chronic Myeloid Leukemia Carrying the T315I Mutation in a Phase 1 Trial
We report results from the largest cohort: pts with confirmed T315I mut at screening (tested locally by Sanger sequencing) and treated with asciminib 200 mg BID, which showed the most robust efficacy (data cutoff: April 30, 2018).At the data cutoff, treatment was ongoing in 23/24 pts (95.8%) (Table); 1 pt (4.2%) had ended treatment. Median duration of follow-up and asciminib exposure were both 28.5 wk (range, 0.1-74.7 wk). Most pts had received multiple prior TKIs, and PON was the most recent TKI for 12/24 (50.0%). Pts who were PON naive had underlying conditions, such as CV risk factors. Eight of 24 pts achieved MMR by 24...
Source: Blood - November 21, 2018 Category: Hematology Authors: Rea, D., Lang, F., Kim, D.-W., Cortes, J. E., Hughes, T. P., Minami, H., Breccia, M., Deangelo, D. J., Hochhaus, A., Talpaz, M., Goh, Y. T., le Coutre, P., Deininger, M. W., Etienne, G., Sondhi, M., Mishra, K., Aimone, P., Ng-Sikorski, J., Mauro, M. J. Tags: 632. Chronic Myeloid Leukemia: Therapy: TFR Failure, Resistance, and New Drug Development Source Type: research
A Genetic Variant in GOLGB1 Affects Golgi Function and Stroke Risk in Patients with Sickle Cell Disease
Conclusions: Our study has shown that a coding variant in GOLGB1, identified as protective against risk of stroke in patients with SCD, has significant effects on Golgi function in SCD samples. We observed that having the GOLGB1 Y1212C variant resulted in more compact and less fragmented Golgi apparatus. Proteomic analysis showed that SCD patients with the GOLGB1 variant also had significantly lower levels of proteins involved in platelet activation and Golgi trafficking. Our findings suggest a novel role for the Golgi apparatus in controlling protein flux that modulates risk of stroke in SCD.DisclosuresNo relevant conflic...
Source: Blood - November 21, 2018 Category: Hematology Authors: Kotu, V., Dubrelle, J., Baker, J., Jenson, K., Flanagan, J. M. Tags: 113. Hemoglobinopathies, Excluding Thalassemia-Basic and Translational Science: Poster III Source Type: research
Elevated Levels of CD64 MFI on Monocyte Subsets Are Associated with a History of Stroke in Sickle Cell Disease
Conclusion: Levels of monocyte subsets have been shown to correlate with clinical outcomes in non-SCD stroke, but to our knowledge this is the first study to examine their roles in ischemic stroke in SCD. The pathophysiology of stroke in SCD is unique and the role of monocytes in it deserves separate study from the role of monocytes in non-SCD stroke. We saw that while monocyte subsets were associated with a history of ischemic stroke, CD64 MFI on all monocyte subsets showed a strong association. We wonder if this may be due to CD64 MFI being a marker for cells which are more adherent to endothelium as has been shown in pr...
Source: Blood - November 21, 2018 Category: Hematology Authors: Curtis, S. A., Balbuena-Merle, R., Devine, L., Zelterman, D., Roberts, J. D., Dearborn-Tomazos, J., Sansing, L., Hendrickson, J. E. Tags: 114. Hemoglobinopathies, Excluding Thalassemia-Clinical: Poster I Source Type: research
The Role of Hydroxyurea to Prevent Silent Stroke in Sickle Cell Disease: Systematic Review and Meta-Analysis
Chronic blood transfusions are standard of care for stroke prevention in sickle cell disease. We evaluated hydroxyurea's efficacy in preventing silent stroke. We searched for randomized controlled trials (RCTs) and observational studies on Pubmed, CENTRAL, Embase, and Web of Science without using language/time limits. Eligible studies compared hydroxyurea with transfusions or observation to prevent silent stroke. This systematic review adheres to the Cochrane guidelines. Data were pooled using random effects model using STATA to perform meta-analysis. Methodological quality of RCTs was investigated using the Cochrane risk ...
Source: Blood - November 21, 2018 Category: Hematology Authors: Hasson, C., Veling, L., Rico, J. F., Mhaskar, R. Tags: 114. Hemoglobinopathies, Excluding Thalassemia-Clinical: Poster II Source Type: research
Middle Cerebral Artery Velocities Are Inversely Related to Hemoglobin Levels and Acutely Drop in Response to RBC Transfusion: Implications for Stroke Screening in SCD
DiscussionThese data show a striking relationship between anemia and TCD velocity, and that RBC transfusion can alter MCA velocity. Even an 11% increase in hemoglobin such as that seen in the low-responder in Figure 3 could change a patient classification from high-risk to conditional TCD. These data also show the significant sensitivity of MCA velocity to the depth of measurement (Figure 2 & 3). The investigators in the STOP study went to extreme ends to standardize these measurements. Nonetheless, TCD measures may not be done with such rigor in clinical settings. It is clear that standard TCD screening has been of tr...
Source: Blood - November 21, 2018 Category: Hematology Authors: Perumbeti, A., Carreras, O., Detterich, J. A., Shah, P., Sunwoo, J., Khoo, M., Wood, J. C., Coates, T. D. Tags: 114. Hemoglobinopathies, Excluding Thalassemia-Clinical: Poster II Source Type: research
Results from the Displace Consortium: Practice Patterns on the Use of Transcranial Doppler Screening for Risk of Stroke in Children with Sickle Cell Anemia
Conclusions: Nearly all DISPLACE sites order TCD screening annually, as recommended in the guidelines, with some ordering screening more frequently. A few sites did not report initiation of CRCT per STOP protocol for abnormal TCD results; however, over half of the sites reported following up with an MRI/MRA, which may suggest evaluating for vasculopathy prior to CRCT. Some sites reported beginning HU therapy for abnormal results; this may reflect consideration of patients for whom CRCT is not possible, but data were not collected for confirmation. Interestingly, results suggest a reliance on MRI/MRA since sites commonly re...
Source: Blood - November 21, 2018 Category: Hematology Authors: Phillips, S., Mueller, M., Schlenz, A. M., Melvin, C., Adams, R. J., Kanter, J. Tags: 901. Health Services Research-Non-Malignant Conditions: Poster III Source Type: research
PAR1 biased signaling is required for activated protein C in vivo benefits in sepsis and stroke
Activated protein C (APC) cleaves protease-activated receptor 1 (PAR1) in vitro at R46 to initiate beneficial cell signaling; however, thrombin and APC can cleave at R41. To elucidate PAR1-dependent aspects of the pharmacologic in vivo mechanisms of APC, we generated C57BL/6 mouse strains carrying QQ41 or QQ46 point mutations in PAR1 (F2r gene). Using these strains, we determined whether or not recombinant murine signaling-selective APC mutants would reduce septic death or provide neuroprotection against ischemic stroke when mice carried PAR1-homozygous mutations that prevent cleavage at either R41 or R46. Intercrossing PA...
Source: Blood - March 15, 2018 Category: Hematology Authors: Sinha, R. K., Wang, Y., Zhao, Z., Xu, X., Burnier, L., Gupta, N., Fernandez, J. A., Martin, G., Kupriyanov, S., Mosnier, L. O., Zlokovic, B. V., Griffin, J. H. Tags: Plenary Papers, Thrombosis and Hemostasis, Vascular Biology Source Type: research
ADAMTS13 controls vascular remodeling by modifying VWF reactivity during stroke recovery
Angiogenic response is essential for ischemic brain repair. The von Willebrand factor (VWF)–cleaving protease disintegrin and metalloprotease with thrombospondin type I motif, member 13 (ADAMTS13) is required for endothelial tube formation in vitro, but there is currently no in vivo evidence supporting a function of ADAMTS13 in angiogenesis. Here we show that mice deficient in ADAMTS13 exhibited reduced neovascularization, brain capillary perfusion, pericyte and smooth muscle cell coverage on microvessels, expression of the tight junction and basement membrane proteins, and accelerated blood-brain barrier (BBB) break...
Source: Blood - July 6, 2017 Category: Hematology Authors: Xu, H., Cao, Y., Yang, X., Cai, P., Kang, L., Zhu, X., Luo, H., Lu, L., Wei, L., Bai, X., Zhu, Y., Zhao, B.-Q., Fan, W. Tags: Plenary Papers, Thrombosis and Hemostasis, Vascular Biology 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
Plasma kallikrein mediates brain hemorrhage and edema caused by tissue plasminogen activator therapy in mice after stroke
Thrombolytic therapy using tissue plasminogen activator (tPA) in acute stroke is associated with increased risks of cerebral hemorrhagic transformation and angioedema. Although plasma kallikrein (PKal) has been implicated in contributing to both hematoma expansion and thrombosis in stroke, its role in the complications associated with the therapeutic use of tPA in stroke is not yet available. We investigated the effects of tPA on plasma prekallikrein (PPK) activation and the role of PKal on cerebral outcomes in a murine thrombotic stroke model treated with tPA. We show that tPA increases PKal activity in vitro in both muri...
Source: Blood - April 20, 2017 Category: Hematology Authors: Simao, F., Ustunkaya, T., Clermont, A. C., Feener, E. P. Tags: Thrombosis and Hemostasis Source Type: research
ADAMTS13-mediated thrombolysis of t-PA-resistant occlusions in ischemic stroke in mice
Rapid vascular recanalization forms the basis for successful treatment of cerebral ischemia. Currently, tissue plasminogen activator (t-PA) is the only approved thrombolytic drug for ischemic stroke. However, t-PA does not always result in efficient thrombus dissolution and subsequent blood vessel recanalization. To better understand thrombus composition, we analyzed thrombi retrieved from ischemic stroke patients and found a distinct presence of von Willebrand factor (VWF) in various samples. Thrombi contained on average 20.3% ± 10.1% VWF, and this was inversely correlated with thrombus red blood cell content. We h...
Source: Blood - May 12, 2016 Category: Hematology Authors: Denorme, F., Langhauser, F., Desender, L., Vandenbulcke, A., Rottensteiner, H., Plaimauer, B., Francois, O., Andersson, T., Deckmyn, H., Scheiflinger, F., Kleinschnitz, C., Vanhoorelbeke, K., De Meyer, S. F. Tags: Thrombosis and Hemostasis Source Type: research
Plasma L5 levels are elevated in ischemic stroke patients and enhance platelet aggregation
L5, the most electronegative and atherogenic subfraction of low-density lipoprotein (LDL), induces platelet activation. We hypothesized that plasma L5 levels are increased in acute ischemic stroke patients and examined whether lectin-like oxidized LDL receptor-1 (LOX-1), the receptor for L5 on endothelial cells and platelets, plays a critical role in stroke. Because amyloid β (Aβ) stimulates platelet aggregation, we studied whether L5 and Aβ function synergistically to induce prothrombotic pathways leading to stroke. Levels of plasma L5, serum Aβ, and platelet LOX-1 expression were significantly higher ...
Source: Blood - March 10, 2016 Category: Hematology Authors: Shen, M.-Y., Chen, F.-Y., Hsu, J.-F., Fu, R.-H., Chang, C.-M., Chang, C.-T., Liu, C.-H., Wu, J.-R., Lee, A.-S., Chan, H.-C., Sheu, J.-R., Lin, S.-Z., Shyu, W.-C., Sawamura, T., Chang, K.-C., Hsu, C. Y., Chen, C.-H. Tags: Free Research Articles, Platelets and Thrombopoiesis, Thrombosis and Hemostasis Source Type: research
Low ADAMTS13 activity is associated with an increased risk of ischemic stroke
ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin motif repeats 13) has antithrombotic properties because it cleaves von Willebrand factor (VWF) in smaller, less active multimers. The aim of our study was to investigate prospectively the association between ADAMTS13 activity and ischemic stroke. We included 5941 individuals ≥55 years without a history of stroke or transient ischemic attack (TIA) of the Rotterdam Study, a population-based cohort study. ADAMTS13 activity was measured at inclusion with the FRETS-VWF73 assay and VWF antigen (VWF:Ag) levels by enzyme-linked immunosorbent assay. We assessed ...
Source: Blood - December 17, 2015 Category: Hematology Authors: Sonneveld, M. A. H., de Maat, M. P. M., Portegies, M. L. P., Kavousi, M., Hofman, A., Turecek, P. L., Rottensteiner, H., Scheiflinger, F., Koudstaal, P. J., Ikram, M. A., Leebeek, F. W. G. Tags: Free Research Articles, Thrombosis and Hemostasis, Clinical Trials and Observations Source Type: research
Platelet-derived VWF is not essential for normal thrombosis and hemostasis but fosters ischemic stroke injury in mice
Von Willebrand factor (VWF) is a key hemostatic protein synthesized in both endothelial cells and megakaryocytes. Megakaryocyte-derived VWF is stored in α-granules of platelets and is enriched in hyperactive "ultra-large" VWF multimers. To elucidate the specific contribution of platelet VWF in hemostasis and thrombosis, we performed crossed bone marrow transplantations between C57BL/6J and Vwf–/– mice to generate chimeric mice. Chimeric mice specifically lacking platelet VWF showed normal tail bleeding and carotid artery thrombosis, similar to wild-type mice. Chimeric mice with VWF present only in platele...
Source: Blood - October 1, 2015 Category: Hematology Authors: Verhenne, S., Denorme, F., Libbrecht, S., Vandenbulcke, A., Pareyn, I., Deckmyn, H., Lambrecht, A., Nieswandt, B., Kleinschnitz, C., Vanhoorelbeke, K., De Meyer, S. F. Tags: Platelets and Thrombopoiesis, Thrombosis and Hemostasis Source Type: research
Innovative thrombolytic strategy using a heterodimer diabody against TAFI and PAI-1 in mouse models of thrombosis and stroke
In conclusion, administration of a bispecific inhibitor against TAFI and PAI-1 results in a prominent profibrinolytic effect in mice without increased bleeding.
Source: Blood - February 19, 2015 Category: Hematology Authors: Wyseure, T., Rubio, M., Denorme, F., Martinez de Lizarrondo, S., Peeters, M., Gils, A., De Meyer, S. F., Vivien, D., Declerck, P. J. Tags: Thrombosis and Hemostasis Source Type: research
SLAP/SLAP2 prevent excessive platelet (hem)ITAM signaling in thrombosis and ischemic stroke in mice
In this study, we show that platelets expressed both SLAP isoforms and that overexpression of either protein in a heterologous cell line almost completely inhibited glycoprotein VI and C-type lectin-like receptor 2 signaling. In mice, single deficiency of SLAP or SLAP2 had only moderate effects on platelet function, whereas double deficiency of both adapters resulted in markedly increased signal transduction, integrin activation, granule release, aggregation, procoagulant activity, and thrombin generation in response to (hem)ITAM-coupled, but not G protein-coupled, receptor activation. In vivo, constitutive SLAP/SLAP2 knoc...
Source: Blood - January 1, 2015 Category: Hematology Authors: Cherpokova, D., Bender, M., Morowski, M., Kraft, P., Schuhmann, M. K., Akbar, S. M., Sultan, C. S., Hughes, C. E., Kleinschnitz, C., Stoll, G., Dragone, L. L., Watson, S. P., Tomlinson, M. G., Nieswandt, B. Tags: Free Research Articles, Platelets and Thrombopoiesis, Thrombosis and Hemostasis Source Type: research