Allogeneic stem cell transplantation is curative in aplastic anemia with much less intrinsic toxicity than transplantation in hematologic malignancies. The recent BMT-CTN trial demonstrated 97% survival at one year with little subsequent decline. However patients without matched related or unrelated donors have graft-rejection rates of up to 50%. Preliminary data from the Netherlands suggests that anti-thymocyte globulin...
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Apheresis Medicine in the Management of Sickle Cell Disease
Despite advances in care, patients with sickle cell disease have significant morbidity and mortality. One challenge is the optimal use of simple vs exchange transfusion vs no transfusion when managing these patients. Simple transfusions lead to iron overload while exchange transfusions may expose patients to increase numbers of red blood cell units. The mechanism of benefit from transfusion (oxygen delivery vs marrow...
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How can we non-invasively, but still accurately, measure blood pressure in the pulmonary arteries?
Pulmonary hypertension (PH) is a complex, progressive condition characterized by high blood pressure in the lungs. The gold standard for measuring pressures in the pulmonary arteries is a right heart catheterization, where a special catheter is guided through the right side of the heart and into the pulmonary artery, the main vessel carrying blood to the lungs. This measurement is essential, as it allows physicians and...
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Would patients with pulmonary arterial hypertension (PAH) benefit from background anticoagulation in addition to their PAH-targe
Pulmonary hypertension (PH) is a complex, progressive condition characterized by high blood pressure in the lungs. For several decades, oral anticoagulation has been recommended by some societies for patients with a specific form of PH called pulmonary arterial hypertension. However, the evidence currently supporting this recommendation is very limited. To date, no prospective randomized clinical trial has been completed...
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How can we increase the pharmaceutical clinical research of targeted therapies in pediatric PAH patients, including encouraging
Clinical research, especially randomized pharmaceutical clinical trials, poses many unique challenges compared to research in adult subjects. In pulmonary arterial hypertension, a disease characterized by high blood pressure of the lungs with increased pulmonary vascular resistance leading to right ventricular failure, there are 12 FDA-approved PAH-targeted therapies for adults. None of these medications are currently...
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In pulmonary arterial hypertension (PAH), how can right ventricular function be improved in the setting of increased afterload
Pulmonary arterial hypertension (PAH) is a complex, progressive condition characterized by high blood pressure in the lungs and restriction of flow through the pulmonary arterial system. Significant improvements have been made in medical management with through approved pulmonary vasodilator therapies. However, long-term right ventricular afterload reductions have still not yet been achieved. The process by which the...
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Development of right ventricular-targeted therapies in pulmonary arterial hypertension (PAH)
Pulmonary arterial hypertension (PAH) is a complex, progressive condition characterized by high blood pressure in the lungs and restriction of flow through the pulmonary arterial system. A great increase in the treatment armamentarium has been noted for this rare disease in the past 20 years, with 12 new PAH-targeted therapies. Though these therapies do improve cardiac performance, this is most likely due to their primary...
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Anemia, oxygen delivery, and red blood cell transfusion
In neonatal, pediatric, and adult patients with critical illness, what is the best means to identify: (1) the degree to which anemia contributes to insufficient oxygen (O2) delivery and (2) the likelihood that O2 delivery will be improved by red blood cell (RBC) transfusion?
These questions are most relevant to critically ill populations that exhibit unique physiology, including those with low cardiac output (cardiac... more »
These questions are most relevant to critically ill populations that exhibit unique physiology, including those with low cardiac output (cardiac... more »
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Biology of Red Blood Cell Alloimmunization
What determines which individuals will develop RBC alloimmune responses resulting in clinically meaningful sequelae?
This question encompasses: 1) the generation of alloantibodies that limit the availability of compatible blood or cause hemolytic disease of the fetus or newborn (HDFN); 2) the distinction between clinically significant and insignificant alloantibody responses, especially within alloantibody specificities... more »
This question encompasses: 1) the generation of alloantibodies that limit the availability of compatible blood or cause hemolytic disease of the fetus or newborn (HDFN); 2) the distinction between clinically significant and insignificant alloantibody responses, especially within alloantibody specificities... more »
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Evidence based approaches to Red Blood Cell transfusion
What are the optimal RBC transfusion thresholds for adult and pediatric cancer patients undergoing chemotherapy regimens that may improve functional status and quality of life?
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Stem Cell Biology
There is a need to develop an artificial and functional hematopoietic stem cell (HSC) niche that allows for the expansion of repopulating HSCs.
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What new methods of platelet preparation, processing, and storage are needed for hemostasis in various clinical conditions?
The limitations of 5-day 22˚ C storage significantly impacts platelet availability. It is critical that we develop new methods of collection, processing, storage to extend the storage time of platelets, and evaluate the use of whole blood. The attributes of these products must be understood to optimally alignment product attributes, clinical efficacy and safety with hemostatic needs in a variety of clinical states. Specifically,...
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Blood Donor and Component Factors that Influence Clinical Outcomes of Transfusion
Are donor factors (age/sex), whole blood processing methods and/or red cell storage solutions associated with in-hospital mortality and/or other measures of transfusion efficacy or harm in patients who have received red cell transfusions?
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The potency and safety of transfusable red blood cells
Can we identify approaches to improve potency and/or safety of transfusable RBCs?
42 day pre-transfusion storage of RBCs maximizes utilization, while minimizing waste. However, RBCs undergo changes during collection, manipulation and storage that may reduce their potency or safety. Progress in understanding markers that predict transfusion success at the time of collection and with storage remains slow. New technologies... more »
42 day pre-transfusion storage of RBCs maximizes utilization, while minimizing waste. However, RBCs undergo changes during collection, manipulation and storage that may reduce their potency or safety. Progress in understanding markers that predict transfusion success at the time of collection and with storage remains slow. New technologies... more »
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Inflammation: what is the role of the blood microbiome?
Blood is not continuously sterile. Data from dental studies, blood donors, and random blood cultures document that "normal" human blood often harbors microbes. Sepsis only occurs when immunological regulatory systems fail. Growing evidence link subclinical, potentially transient bacteremia to cardiovascular and other diseases. Could many of the diseases associated with inflammatory markers represent either continuous...
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