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New research suggests that increased red blood cell distribution width (RDW) is caused by reduced clearance of aging red blood cells (RBCs) from the bloodstream.
And previous studies showed that elevations in RDW predict the development, progression, and risk of death from many conditions.
“It appears that the human body slightly slows down the production and destruction of red blood cells in just about every major disease,” said John Higgins, MD, of Massachusetts General Hospital in Boston.
“If we can accurately measure the production or destruction rates, we might be able to identify many of these diseases in their earlier stages when they are most treatable. Existing measures of the production rate are far too imprecise to detect these subtle changes, but this paper shows how the destruction rate can be estimated using existing blood count data and a mathematical model.”
The paper has been published in the American Journal of Hematology.
Healthy adults generate RBCs at a rate of more than 2 million per second, and the cells circulate in the bloodstream for 100 to 120 days, during which their size decreases by around 30%. Aged RBCs are then cleared at about the same rate of 2 million per second.
Prior to the reports linking elevated RDW with an increased risk for many diseases, that measure had only been used to help distinguish between different forms of anemia.
To understand the correlation between RDW and disease prognosis, Dr Higgins and his colleagues analyzed raw data from more than 60,000 randomly selected blood samples. They used a mathematical model to replicate how RBC populations behave differently in health and in disease.
The researchers measured the extent to which RBCs in different phases of their life cycle contribute to increased RDW and found that the variance in size was strongly determined by mild increases in the numbers of the smallest and oldest cells.
Since the most important mechanism controlling the number of the oldest cells is the rate at which they are cleared from the bloodstream, the team made several predictions, which were validated by applying their model to clinical data from the blood samples and to data from several published studies.
The researchers found that increased RDW was associated with delayed RBC clearance, and increased RDW was associated with increased average age of RBCs.
Delayed RBC clearance was as strongly associated with overall risk of death, as was increased RDW, and delayed RBC clearance was associated with the presence of early signs of hidden diseases associated with increased RDW.
Patients with delayed RBC clearance had a greater risk of developing signs of those diseases in the future than patients with a typical clearance rate. In healthy patients, the rate of RBC clearance varied less than any other traditional blood-count characteristic.
Dr Higgins said there are many potential clinical applications of these findings, which need to be validated by future studies.
“Finding a reduced clearance rate in an apparently healthy person would likely mean that an underlying disease process was developing—such as the early stages of iron deficiency, kidney disease, colon cancer, or congestive heart failure—and would warrant further diagnostic evaluation,” Dr Higgins said.
“Based on this analysis of routine blood tests, a primary care physician could immediately consider appropriate follow-up diagnostic testing, instead of waiting for other signs and symptoms to appear as the condition progresses. In a patient with established disease, a reduced clearance rate could mean progression of disease or treatment failure, and imminent complications could be avoided or reduced by adjusting treatment right away or at least by more frequent monitoring.”
“In addition to confirming our findings in prospective studies that would follow a group of patients over time, we hope to identify the diseases for which an early warning provided by delayed clearance would lead to the most significant improvements in patient outcomes. We’d also like to understand more about the processes controlling red blood cell clearance and are actively developing similar models for populations of white blood cells and platelets.” 
New research suggests that increased red blood cell distribution width (RDW) is caused by reduced clearance of aging red blood cells (RBCs) from the bloodstream.
And previous studies showed that elevations in RDW predict the development, progression, and risk of death from many conditions.
“It appears that the human body slightly slows down the production and destruction of red blood cells in just about every major disease,” said John Higgins, MD, of Massachusetts General Hospital in Boston.
“If we can accurately measure the production or destruction rates, we might be able to identify many of these diseases in their earlier stages when they are most treatable. Existing measures of the production rate are far too imprecise to detect these subtle changes, but this paper shows how the destruction rate can be estimated using existing blood count data and a mathematical model.”
The paper has been published in the American Journal of Hematology.
Healthy adults generate RBCs at a rate of more than 2 million per second, and the cells circulate in the bloodstream for 100 to 120 days, during which their size decreases by around 30%. Aged RBCs are then cleared at about the same rate of 2 million per second.
Prior to the reports linking elevated RDW with an increased risk for many diseases, that measure had only been used to help distinguish between different forms of anemia.
To understand the correlation between RDW and disease prognosis, Dr Higgins and his colleagues analyzed raw data from more than 60,000 randomly selected blood samples. They used a mathematical model to replicate how RBC populations behave differently in health and in disease.
The researchers measured the extent to which RBCs in different phases of their life cycle contribute to increased RDW and found that the variance in size was strongly determined by mild increases in the numbers of the smallest and oldest cells.
Since the most important mechanism controlling the number of the oldest cells is the rate at which they are cleared from the bloodstream, the team made several predictions, which were validated by applying their model to clinical data from the blood samples and to data from several published studies.
The researchers found that increased RDW was associated with delayed RBC clearance, and increased RDW was associated with increased average age of RBCs.
Delayed RBC clearance was as strongly associated with overall risk of death, as was increased RDW, and delayed RBC clearance was associated with the presence of early signs of hidden diseases associated with increased RDW.
Patients with delayed RBC clearance had a greater risk of developing signs of those diseases in the future than patients with a typical clearance rate. In healthy patients, the rate of RBC clearance varied less than any other traditional blood-count characteristic.
Dr Higgins said there are many potential clinical applications of these findings, which need to be validated by future studies.
“Finding a reduced clearance rate in an apparently healthy person would likely mean that an underlying disease process was developing—such as the early stages of iron deficiency, kidney disease, colon cancer, or congestive heart failure—and would warrant further diagnostic evaluation,” Dr Higgins said.
“Based on this analysis of routine blood tests, a primary care physician could immediately consider appropriate follow-up diagnostic testing, instead of waiting for other signs and symptoms to appear as the condition progresses. In a patient with established disease, a reduced clearance rate could mean progression of disease or treatment failure, and imminent complications could be avoided or reduced by adjusting treatment right away or at least by more frequent monitoring.”
“In addition to confirming our findings in prospective studies that would follow a group of patients over time, we hope to identify the diseases for which an early warning provided by delayed clearance would lead to the most significant improvements in patient outcomes. We’d also like to understand more about the processes controlling red blood cell clearance and are actively developing similar models for populations of white blood cells and platelets.”
New research suggests that increased red blood cell distribution width (RDW) is caused by reduced clearance of aging red blood cells (RBCs) from the bloodstream.
And previous studies showed that elevations in RDW predict the development, progression, and risk of death from many conditions.
“It appears that the human body slightly slows down the production and destruction of red blood cells in just about every major disease,” said John Higgins, MD, of Massachusetts General Hospital in Boston.
“If we can accurately measure the production or destruction rates, we might be able to identify many of these diseases in their earlier stages when they are most treatable. Existing measures of the production rate are far too imprecise to detect these subtle changes, but this paper shows how the destruction rate can be estimated using existing blood count data and a mathematical model.”
The paper has been published in the American Journal of Hematology.
Healthy adults generate RBCs at a rate of more than 2 million per second, and the cells circulate in the bloodstream for 100 to 120 days, during which their size decreases by around 30%. Aged RBCs are then cleared at about the same rate of 2 million per second.
Prior to the reports linking elevated RDW with an increased risk for many diseases, that measure had only been used to help distinguish between different forms of anemia.
To understand the correlation between RDW and disease prognosis, Dr Higgins and his colleagues analyzed raw data from more than 60,000 randomly selected blood samples. They used a mathematical model to replicate how RBC populations behave differently in health and in disease.
The researchers measured the extent to which RBCs in different phases of their life cycle contribute to increased RDW and found that the variance in size was strongly determined by mild increases in the numbers of the smallest and oldest cells.
Since the most important mechanism controlling the number of the oldest cells is the rate at which they are cleared from the bloodstream, the team made several predictions, which were validated by applying their model to clinical data from the blood samples and to data from several published studies.
The researchers found that increased RDW was associated with delayed RBC clearance, and increased RDW was associated with increased average age of RBCs.
Delayed RBC clearance was as strongly associated with overall risk of death, as was increased RDW, and delayed RBC clearance was associated with the presence of early signs of hidden diseases associated with increased RDW.
Patients with delayed RBC clearance had a greater risk of developing signs of those diseases in the future than patients with a typical clearance rate. In healthy patients, the rate of RBC clearance varied less than any other traditional blood-count characteristic.
Dr Higgins said there are many potential clinical applications of these findings, which need to be validated by future studies.
“Finding a reduced clearance rate in an apparently healthy person would likely mean that an underlying disease process was developing—such as the early stages of iron deficiency, kidney disease, colon cancer, or congestive heart failure—and would warrant further diagnostic evaluation,” Dr Higgins said.
“Based on this analysis of routine blood tests, a primary care physician could immediately consider appropriate follow-up diagnostic testing, instead of waiting for other signs and symptoms to appear as the condition progresses. In a patient with established disease, a reduced clearance rate could mean progression of disease or treatment failure, and imminent complications could be avoided or reduced by adjusting treatment right away or at least by more frequent monitoring.”
“In addition to confirming our findings in prospective studies that would follow a group of patients over time, we hope to identify the diseases for which an early warning provided by delayed clearance would lead to the most significant improvements in patient outcomes. We’d also like to understand more about the processes controlling red blood cell clearance and are actively developing similar models for populations of white blood cells and platelets.”