Showing 2 ideas for tag "exchange"

Goal 2: Reduce Human Disease

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... more »

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

Details on the impact of addressing this CQ or CC

SCD is the most common genetic disease in the United States affecting 100,000 individuals or 1 in 400 African American births. Pain, stroke, acute chest syndrome and priapism are common morbidities affecting patients with sickle cell disease, which often result in emergency room visits and/or hospitalizations. Despite advances in treatment, sickle cell disease is associated with significant mortality and shortened life expectancy. Defining the optimal role of red blood cell exchange and plasma exchange (which may be used to remove plasma molecules such as inflammatory factors and free hemoglobin) in the management and prevention of the complications of sickle cell disease and may not only prolong the life of these patients but is expected to improve the quality of their lives. In addition, clearly defining the indications for simple verses exchange transfusion therapy has the potential to minimize both alloimmunization to red blood cells (reported to occur in up to 75% of patients with sickle cell disease) and iron overload associated with transfusion.

Transfusion therapy may be efficacious to sickle cell patients by providing increased oxygen delivery to tissues and/or decreasing the amount of sickle hemoglobin present by suppression of erythropoiesis. Understanding the relative contributions of these mechanisms will assist with optimal use of transfusion therapy as well as inform the development of novel alternative therapies

Feasibility and challenges of addressing this CQ or CC

Multi-center trials should be feasible, given the number of patients with sickle cell disease in the US. Participation by larger academic centers which care for sickle cell patients should facilitate trials. Methods for automated red cell exchange and plasma exchange are available and in common use at many centers. Great interest exists among physicians caring for sickle cell patients (as exemplified by the recent NIH consensus document and ASFA sickle cell consensus conference) which is a strength of this proposal. Challenges include agreement on standard treatment protocols across centers and long term follow up of patients. Maintaining vascular access in sickle cell patients is another challenge when performing apheresis procedures on sickle cell patients

Name of idea submitter and other team members who worked on this idea Bruce Sachais on behalf of ASFA

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Goal 3: Advance Translational Research

Immunologic predictors of cardiac function following apheresis for dilated cardiomyopathy

Apheresis has been used to treat dilated cardiomyopathy yet the mechanism of action and predictors of response are unknown and clinical utility needs to be confirmed. What is the clinical utility, mechanism of action, and predictors of response?

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

Details on the impact of addressing this CQ or CC

Dilated cardiomyopathy (DCM) is progressive ventricular enlargement and dysfunction, responsible for 10,000 deaths and 46,000 hospitalizations in the U.S. annually. It is the primary indication for heart transplantation. It may represent viral infection triggered autoimmunity with myocardial autoantibodies identified in 80% of patients and higher autoimmune disease prevalence in patients.

Immunoadsorption and plasma exchange have been used to treat DCM. Staphylococcal protein A agarose (SPAA) columns have the largest published evidence with improved left ventricular (LV)ejection fraction, decreased LV circumference, decreased BNP, improved exercise tolerance, improved oxygen uptake, increased regulator T-cells, decreased stimulatory T-cells, decreased costimulatory T-cells, and improved quality of life. Decreased morbidity and mortality with fewer patients progressing to transplantation and lower health care costs has been described. Given organ shortages, morbidity, and expense of transplantation, a treatment that delays or avoids transplantation would improve health and reduced costs.

Immunological variables such as IgG subtypes, Th1, Th2, Th17 and T regulatory cell number, associated cytokines, and nuclear transcription factors implicated in DCM pathogenesis could correlate with LV function following apheresis and identify apheresis selection criteria and offer a novel mechanism to investigate how autoantibody reduction influences cellular immune components.

Feasibility and challenges of addressing this CQ or CC

DCM is the most common cause of cardiac transplantation with a large number of patients available for study. There are numerous standardized tools for measuring patient quality of life and function for those suffering from congestive heart failure. There are readily available assays for examining potential immunologic variables. If TPE is examined, this procedure is readily available.

Challenges would include the fact that the immunoadsorption columns that have been used are not cleared by the Food and Drug Administration and therefore there is limited to no experience with their use in the U.S. Immunologic evaluations could also require endomyocardial biopsy which represents an invasive procedure which could limit patient enrollment and increase risk.

Name of idea submitter and other team members who worked on this idea Bruce Saichais on behalf of ASFA

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