Showing 5 ideas for tag "hemoglobin"

Goal 1: Promote Human Health

Epigenetics and Genomics

There is a need to investigate hemoglobin biosynthesis in order to develop novel approaches to treat sickle cell disease, thalassemia, and other anemias.

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Studies on epigenetic mechanisms have extraordinary promise for the development of transformative therapeutic approaches for non-malignant hematologic disorders, however, limited progress has been made in advancing therapies to counteract the often crippling complications of these conditions. In the case of sickle cell disease, an ensemble of proteins has been implicated in mediating the epigenetic repression of gamma-globin expression, raising the possibility that antagonizing the actions of these proteins to increase gamma-globin expression may be a useful treatment strategy. However, in certain cases, some of these proteins are deemed “undruggable,” based on their structural attributes. There is a critical need to identify druggable components of the multi-step epigenetic mechanisms as well as develop better models and assays that will more effectively identify modulators of “undruggable” proteins. Given the rich proteome and improved technologies available today, studies of proteomics, metabolomics, and regulatory RNAs are likely to reveal promising translational avenues. In addition, approaches to modifying the expression of the components of this pathway are underway using developing gene therapy strategies, such as viral vectors and/or gene editing can quickly advance therapy in sickle cell disease and β-thalassmia.

Name of idea submitter and other team members who worked on this idea Alice Kuaban on behalf of the American Society of Hematology (ASH)

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62 up votes
20 down votes
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Goal 3: Advance Translational Research

Develop alternatives for patients for whom routine red cell transfusion is unavailable or impractical

There is a compelling need to advance research to understand the physiology governing the safety and efficacy of hemoglobin-based oxygen therapeutics functioning outside the red cell.

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Adequate numbers of red blood cells are required to sustain human life. Neurocognitive deficits and mortality in acutely anemic humans increase significantly at a hemoglobin level of below 5 g/dL even in the absence of significant cardiovascular disease. At extremely low hemoglobin levels, alternative treatments (supplemental or hyperbaric oxygen, sedation, muscle paralysis and mechanical ventilation) are of only limited benefit and are not without risk. Several classes of patients cannot be routinely transfused with red blood cells. These classes of patients for whom blood is not an option would include patients who will not accept transfusion for religious or personal reasons, patients who due to multiple prior transfusions have developed red cell antibodies without the option for compatible red cells, and massive trauma patients needing treatment in a remote location. The development of cell-free hemoglobin-based oxygen carriers, stable at room temperature and not requiring cross-matching prior to transfusion as a red cell substitute, has been a sought after goal for several decades, yet to date all attempts have met with failure during clinical trials. There is a compelling need to advance research to understand the physiology governing the safety and efficacy of hemoglobin-based oxygen therapeutics functioning outside the red cell.

Feasibility and challenges of addressing this CQ or CC

Multiple physiologic insults and adverse events seen with earlier modified hemoglobins, compared to banked red blood cells, have been described and are now better, but not completely, understood. Advances in hemoglobin modification could allow for successful use in a variety of clinical scenarios with life-saving results. Additional clinical indications could be investigated and established, such as identification of clinical situations where additional oxygen delivery could modulate the effects of chronic ischemic conditions. In addition, the hemoglobin molecule could be modified to deliver additional therapeutic benefit.

Name of idea submitter and other team members who worked on this idea Office of Blood Research and Review, CBER, FDA

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8 net votes
13 up votes
5 down votes
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Goal 2: Reduce Human Disease

Optimal hemoglobin threshold for transfusion in children with ARDS?

Do different hemoglobin transfusion thresholds alter outcomes in children with ARDS? What is the optimal *minimum* transfusion threshold for children with ARDS? What patient-centered outcomes can be affected by transfusion strategies: ventilator free days, time to organ function recovery, duration of intensive care stay, survival?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Name of idea submitter and other team members who worked on this idea Society of Critical Care Medicine Executive Committee/Council

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8 net votes
9 up votes
1 down votes
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Goal 2: Reduce Human Disease

Re-evaluating Hemoglobin Thresholds for Red Blood Cell Transfusion Decisions

Are there specific conditions where a liberal transfusion strategy results in lower 30-day mortality as compared to a restrictive transfusion strategy?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

 Clinical trial data show that in multiple patient populations, a 7 to 8 g/dL hemoglobin threshold for red blood cell transfusion is safe. However, equipoise for transfusion thresholds persists in patients with ischemic heart disease and acute neurological conditions where a higher hemoglobin level may decrease ischemic injury to myocardial and cerebral tissues, respectively. Alternatively, liberal red blood cell transfusion may be associated with adverse outcomes such as pulmonary edema or increased rates of heart failure. In other populations, it is possible that even lower transfusion thresholds than 7 g/dL would be safely tolerated. On the other hand, if a 7 g/dL threshold is found to be superior to a lower threshold, this would establish a minimal appropriate threshold to initiate red blood cell transfusion.

Feasibility and challenges of addressing this CQ or CC

Multicenter clinical trials that utilize markers of oxygen consumption are needed to answer these questions. A pilot study in patients with acute myocardial infarction demonstrated that recruitment was feasible for clinical scenarios in which equipoise exists. An international setting where the safety and availability of the blood supply remain significant issues may be best suited to answer the question of whether transfusion thresholds lower than 7 g/dL are safe.

Name of idea submitter and other team members who worked on this idea Nareg Roubinian, MD and Naomi Luban, MD for the 2015 NHLBI State of the Science in Transfusion Medicine

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-4 net votes
22 up votes
26 down votes
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Goal 3: Advance Translational Research

Role of anemia and iron deficiency anemia on hemoglobin A1C%

Many forms of anemia are associated with lowering HbA1C% but iron deficiency anemia modestly raises HbA1C%. The exact mechanism of anemia and iron deficiency anemia's effect on HbA1c levels is unclear. This impacts our treatment of diabetes mellitus and diabetes mellitus co-morbidity with HIV, Hepatitis C and other diseases in the presence of anemia.

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Hemoglobin A1c (HbA1C%) is a widely used marker for the diagnosis and treatment of diabetes mellitus (DM). Understanding how anemia and iron deficiency anemia affects HbA1C% informs the practitioner on proper dosing of oral and insulin based medication regimens, on the impact of diet and exercise in HbA1C% and erythrocyte turnover, and the incidence and prevalence of DM in sub-populations.

Feasibility and challenges of addressing this CQ or CC

With the advent of continous glucose monitoring, studies can be set up for measuring impact of disease state, medication and lifestyle on erythrocyte and seum glucose in addition to basic science on hemoglobin/RBC changes under varying glucose concentrations

Name of idea submitter and other team members who worked on this idea JocelynR

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-2 net votes
10 up votes
12 down votes
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