Blood Banking

Doctor examines SCD patient

Credit: St Jude Children’s

Research Hospital

Monthly blood transfusions can reduce the risk of silent or overt stroke among children with sickle cell disease (SCD) who previously had a silent stroke, according to a study published in The New England Journal of Medicine.

Children with evidence of silent cerebral infarcts who received monthly blood transfusions for 3 years had a 58% lower risk of suffering repeat silent or overt

strokes than children who did not receive transfusions.

In fact, researchers said the actual benefit of transfusion therapy may be even higher, as 15% of the children who were assigned to receive transfusions either did not receive them or only received them for a brief period.

“The results of our study show that blood transfusions can play a critical role in preventing this insidious and potentially devastating condition,” said study author James F. Casella, MD, of the Johns Hopkins Children’s Center in Baltimore, Maryland.

“They also highlight the importance of intervening early to preclude ongoing or further brain injury among these youngsters. Most importantly, our findings suggest a much-needed treatment option for clinicians and families of children with sickle cell disease who have had silent strokes.”

Previous studies have suggested that blood transfusions may help prevent stroke in patients with SCD by increasing the number of normal red blood cells and decreasing the likelihood of blocked blood vessels.

But Dr Casella and his colleagues wanted to determine if monthly blood transfusions would help prevent stroke in children with SCD who had evidence of a previous silent cerebral infarct, as well as whether the benefits of transfusion outweigh the risks.

The researchers analyzed 196 children, ages 5 to 15 years, who were diagnosed with SCD and had infarct-like lesions on their MRI scans. The children were randomized to an observation arm or to receive blood transfusions every month for 3 years.

Six percent (6/99) of children who received regular transfusions suffered another silent or overt stroke. One of the patients had a stroke, and 5 had new or enlarged silent cerebral infarcts.

In comparison, 14% (14/97) of children in the observation arm experienced a silent or overt stroke. Seven had a stroke, and 7 had new or enlarged silent cerebral infarcts.

So children who did not receive transfusions were more than twice as likely as their peers to have repeat strokes.

Children who did not receive transfusions were also more likely to suffer a range of other SCD-related problems, such as episodes of extreme pain. There were 295 pain episodes among children who did not receive transfusions and 126 episodes among transfused patients.

An unexpected result, according to the researchers, was that intelligence measures were not different between the 2 treatment arms. Previous studies suggested that silent strokes are associated with a 5-point reduction in IQ. The researchers said they plan to explore this finding further.

Nevertheless, this study provides “clear evidence” that transfusions can decrease the progression of silent strokes in children with SCD, said study author Michael R. DeBaun, MD, of  Vanderbilt University in Nashville, Tennessee.

“These results suggest that children who have this disease should be screened early for silent strokes, at least by the time they begin elementary school, to help them manage the disease and to ensure minimal impact on school performance,” he added.

Dr DeBaun and his colleagues said children with SCD should have a surveillance MRI, preferably without sedation, at a young age. Most children with SCD who are at risk for a silent stroke will have one by age 6 years.

The researchers also noted that healthcare providers should discuss treatment options with families to determine if transfusion therapy is appropriate, as there is a risk of transfusion reactions and iron overload.

The decision to transfuse should be made by factoring in each child’s overall health, medical history, and the ability to take time from school for monthly procedures.

The researchers said further study is needed to identify which children with a history of silent strokes are at greatest risk for recurrence so transfusion therapy can be targeted to them.

An editorial related to this study also calls for additional research to determine if the findings can be translated to clinical practice.

Doctor examines SCD patient

Credit: St Jude Children’s

Research Hospital

Monthly blood transfusions can reduce the risk of silent or overt stroke among children with sickle cell disease (SCD) who previously had a silent stroke, according to a study published in The New England Journal of Medicine.

Children with evidence of silent cerebral infarcts who received monthly blood transfusions for 3 years had a 58% lower risk of suffering repeat silent or overt

strokes than children who did not receive transfusions.

In fact, researchers said the actual benefit of transfusion therapy may be even higher, as 15% of the children who were assigned to receive transfusions either did not receive them or only received them for a brief period.

“The results of our study show that blood transfusions can play a critical role in preventing this insidious and potentially devastating condition,” said study author James F. Casella, MD, of the Johns Hopkins Children’s Center in Baltimore, Maryland.

“They also highlight the importance of intervening early to preclude ongoing or further brain injury among these youngsters. Most importantly, our findings suggest a much-needed treatment option for clinicians and families of children with sickle cell disease who have had silent strokes.”

Previous studies have suggested that blood transfusions may help prevent stroke in patients with SCD by increasing the number of normal red blood cells and decreasing the likelihood of blocked blood vessels.

But Dr Casella and his colleagues wanted to determine if monthly blood transfusions would help prevent stroke in children with SCD who had evidence of a previous silent cerebral infarct, as well as whether the benefits of transfusion outweigh the risks.

The researchers analyzed 196 children, ages 5 to 15 years, who were diagnosed with SCD and had infarct-like lesions on their MRI scans. The children were randomized to an observation arm or to receive blood transfusions every month for 3 years.

Six percent (6/99) of children who received regular transfusions suffered another silent or overt stroke. One of the patients had a stroke, and 5 had new or enlarged silent cerebral infarcts.

In comparison, 14% (14/97) of children in the observation arm experienced a silent or overt stroke. Seven had a stroke, and 7 had new or enlarged silent cerebral infarcts.

So children who did not receive transfusions were more than twice as likely as their peers to have repeat strokes.

Children who did not receive transfusions were also more likely to suffer a range of other SCD-related problems, such as episodes of extreme pain. There were 295 pain episodes among children who did not receive transfusions and 126 episodes among transfused patients.

An unexpected result, according to the researchers, was that intelligence measures were not different between the 2 treatment arms. Previous studies suggested that silent strokes are associated with a 5-point reduction in IQ. The researchers said they plan to explore this finding further.

Nevertheless, this study provides “clear evidence” that transfusions can decrease the progression of silent strokes in children with SCD, said study author Michael R. DeBaun, MD, of  Vanderbilt University in Nashville, Tennessee.

“These results suggest that children who have this disease should be screened early for silent strokes, at least by the time they begin elementary school, to help them manage the disease and to ensure minimal impact on school performance,” he added.

Dr DeBaun and his colleagues said children with SCD should have a surveillance MRI, preferably without sedation, at a young age. Most children with SCD who are at risk for a silent stroke will have one by age 6 years.

The researchers also noted that healthcare providers should discuss treatment options with families to determine if transfusion therapy is appropriate, as there is a risk of transfusion reactions and iron overload.

The decision to transfuse should be made by factoring in each child’s overall health, medical history, and the ability to take time from school for monthly procedures.

The researchers said further study is needed to identify which children with a history of silent strokes are at greatest risk for recurrence so transfusion therapy can be targeted to them.

An editorial related to this study also calls for additional research to determine if the findings can be translated to clinical practice.

Doctor examines SCD patient

Credit: St Jude Children’s

Research Hospital

Monthly blood transfusions can reduce the risk of silent or overt stroke among children with sickle cell disease (SCD) who previously had a silent stroke, according to a study published in The New England Journal of Medicine.

Children with evidence of silent cerebral infarcts who received monthly blood transfusions for 3 years had a 58% lower risk of suffering repeat silent or overt

strokes than children who did not receive transfusions.

In fact, researchers said the actual benefit of transfusion therapy may be even higher, as 15% of the children who were assigned to receive transfusions either did not receive them or only received them for a brief period.

“The results of our study show that blood transfusions can play a critical role in preventing this insidious and potentially devastating condition,” said study author James F. Casella, MD, of the Johns Hopkins Children’s Center in Baltimore, Maryland.

“They also highlight the importance of intervening early to preclude ongoing or further brain injury among these youngsters. Most importantly, our findings suggest a much-needed treatment option for clinicians and families of children with sickle cell disease who have had silent strokes.”

Previous studies have suggested that blood transfusions may help prevent stroke in patients with SCD by increasing the number of normal red blood cells and decreasing the likelihood of blocked blood vessels.

But Dr Casella and his colleagues wanted to determine if monthly blood transfusions would help prevent stroke in children with SCD who had evidence of a previous silent cerebral infarct, as well as whether the benefits of transfusion outweigh the risks.

The researchers analyzed 196 children, ages 5 to 15 years, who were diagnosed with SCD and had infarct-like lesions on their MRI scans. The children were randomized to an observation arm or to receive blood transfusions every month for 3 years.

Six percent (6/99) of children who received regular transfusions suffered another silent or overt stroke. One of the patients had a stroke, and 5 had new or enlarged silent cerebral infarcts.

In comparison, 14% (14/97) of children in the observation arm experienced a silent or overt stroke. Seven had a stroke, and 7 had new or enlarged silent cerebral infarcts.

So children who did not receive transfusions were more than twice as likely as their peers to have repeat strokes.

Children who did not receive transfusions were also more likely to suffer a range of other SCD-related problems, such as episodes of extreme pain. There were 295 pain episodes among children who did not receive transfusions and 126 episodes among transfused patients.

An unexpected result, according to the researchers, was that intelligence measures were not different between the 2 treatment arms. Previous studies suggested that silent strokes are associated with a 5-point reduction in IQ. The researchers said they plan to explore this finding further.

Nevertheless, this study provides “clear evidence” that transfusions can decrease the progression of silent strokes in children with SCD, said study author Michael R. DeBaun, MD, of  Vanderbilt University in Nashville, Tennessee.

“These results suggest that children who have this disease should be screened early for silent strokes, at least by the time they begin elementary school, to help them manage the disease and to ensure minimal impact on school performance,” he added.

Dr DeBaun and his colleagues said children with SCD should have a surveillance MRI, preferably without sedation, at a young age. Most children with SCD who are at risk for a silent stroke will have one by age 6 years.

The researchers also noted that healthcare providers should discuss treatment options with families to determine if transfusion therapy is appropriate, as there is a risk of transfusion reactions and iron overload.

The decision to transfuse should be made by factoring in each child’s overall health, medical history, and the ability to take time from school for monthly procedures.

The researchers said further study is needed to identify which children with a history of silent strokes are at greatest risk for recurrence so transfusion therapy can be targeted to them.

An editorial related to this study also calls for additional research to determine if the findings can be translated to clinical practice.

Blood for transfusion

Credit: UAB Hospital

Results of a retrospective study suggest an antifibrinolytic agent can significantly reduce the need for blood transfusions after surgery, without increasing the risk of complications.

The agent, tranexamic acid, has been shown to reduce blood loss during or shortly after major joint surgery, but safety concerns remain because large-scale effectiveness studies are lacking.

So researchers set out to evaluate tranexamic acid in a large sample of surgical patients.

The team recounted their efforts in BMJ.

Stavros Memtsoudis, MD, PhD, of the Hospital for Special Surgery in New York, New York, and his colleagues analyzed data from 872,416 patients who underwent total hip or knee replacement procedures at 510 US hospitals between 2006 and 2012.

The researchers compared patients who received tranexamic acid (at 1000 mg,

2000 mg, or 3000 mg) on the day of surgery to patients who did not. The team adjusted their analysis for factors such as patient age and sex, hospital size and location, the type of procedure, and the anesthesia used.

Results showed that use of tranexamic acid was associated with an up to 69% reduction in the need for blood transfusions. Overall, the rate of allogeneic or autologous transfusion was 7.7% among patients who received tranexamic acid and 20.1% among those who did not (P<0.01).

Tranexamic acid use was also linked to a decreased risk of all complications (1.9% vs 2.6%, P<0.001),  thromboembolic events (0.6% vs 0.8%, P=0.0057), the need for mechanical ventilation (0.1% vs 0.2%, P=0.0003), and admission to an intensive care unit (3.1% vs 7.5%, P<0.001).

The median length of hospital stay was the same for treated and untreated patients—3 days. But the median cost of hospital stay was lower among tranexamic acid-treated patients—$14,890 vs $15,110 (P<0.001).

A tranexamic acid dose of 2000 mg appeared to have the best effectiveness and safety profile. But the researchers said additional studies are needed to establish optimal dosing schemes and assess subgroup-specific effectiveness and safety.

Blood for transfusion

Credit: UAB Hospital

Results of a retrospective study suggest an antifibrinolytic agent can significantly reduce the need for blood transfusions after surgery, without increasing the risk of complications.

The agent, tranexamic acid, has been shown to reduce blood loss during or shortly after major joint surgery, but safety concerns remain because large-scale effectiveness studies are lacking.

So researchers set out to evaluate tranexamic acid in a large sample of surgical patients.

The team recounted their efforts in BMJ.

Stavros Memtsoudis, MD, PhD, of the Hospital for Special Surgery in New York, New York, and his colleagues analyzed data from 872,416 patients who underwent total hip or knee replacement procedures at 510 US hospitals between 2006 and 2012.

The researchers compared patients who received tranexamic acid (at 1000 mg,

2000 mg, or 3000 mg) on the day of surgery to patients who did not. The team adjusted their analysis for factors such as patient age and sex, hospital size and location, the type of procedure, and the anesthesia used.

Results showed that use of tranexamic acid was associated with an up to 69% reduction in the need for blood transfusions. Overall, the rate of allogeneic or autologous transfusion was 7.7% among patients who received tranexamic acid and 20.1% among those who did not (P<0.01).

Tranexamic acid use was also linked to a decreased risk of all complications (1.9% vs 2.6%, P<0.001),  thromboembolic events (0.6% vs 0.8%, P=0.0057), the need for mechanical ventilation (0.1% vs 0.2%, P=0.0003), and admission to an intensive care unit (3.1% vs 7.5%, P<0.001).

The median length of hospital stay was the same for treated and untreated patients—3 days. But the median cost of hospital stay was lower among tranexamic acid-treated patients—$14,890 vs $15,110 (P<0.001).

A tranexamic acid dose of 2000 mg appeared to have the best effectiveness and safety profile. But the researchers said additional studies are needed to establish optimal dosing schemes and assess subgroup-specific effectiveness and safety.

Blood for transfusion

Credit: UAB Hospital

Results of a retrospective study suggest an antifibrinolytic agent can significantly reduce the need for blood transfusions after surgery, without increasing the risk of complications.

The agent, tranexamic acid, has been shown to reduce blood loss during or shortly after major joint surgery, but safety concerns remain because large-scale effectiveness studies are lacking.

So researchers set out to evaluate tranexamic acid in a large sample of surgical patients.

The team recounted their efforts in BMJ.

Stavros Memtsoudis, MD, PhD, of the Hospital for Special Surgery in New York, New York, and his colleagues analyzed data from 872,416 patients who underwent total hip or knee replacement procedures at 510 US hospitals between 2006 and 2012.

The researchers compared patients who received tranexamic acid (at 1000 mg,

2000 mg, or 3000 mg) on the day of surgery to patients who did not. The team adjusted their analysis for factors such as patient age and sex, hospital size and location, the type of procedure, and the anesthesia used.

Results showed that use of tranexamic acid was associated with an up to 69% reduction in the need for blood transfusions. Overall, the rate of allogeneic or autologous transfusion was 7.7% among patients who received tranexamic acid and 20.1% among those who did not (P<0.01).

Tranexamic acid use was also linked to a decreased risk of all complications (1.9% vs 2.6%, P<0.001),  thromboembolic events (0.6% vs 0.8%, P=0.0057), the need for mechanical ventilation (0.1% vs 0.2%, P=0.0003), and admission to an intensive care unit (3.1% vs 7.5%, P<0.001).

The median length of hospital stay was the same for treated and untreated patients—3 days. But the median cost of hospital stay was lower among tranexamic acid-treated patients—$14,890 vs $15,110 (P<0.001).

A tranexamic acid dose of 2000 mg appeared to have the best effectiveness and safety profile. But the researchers said additional studies are needed to establish optimal dosing schemes and assess subgroup-specific effectiveness and safety.

Blood for transfusion

Credit: Elise Amendola

Two groups of scientists have developed new tests to diagnose Creutzfeldt-Jakob disease (CJD).

One test uses samples collected from nasal passages to detect sporadic CJD, and the other uses urine samples to identify variant CJD.

The researchers said these tests provide simple methods for differentiating CJD from other diseases and could help prevent the transmission of CJD via blood

transfusions, transplants, or contaminated surgical instruments.

Both tests are described in The New England Journal of Medicine.

Nasal test for sporadic CJD

In one NEJM article, Byron Caughey, PhD, of the National Institute of Allergy and Infectious Diseases in Rockville, Maryland, and his colleagues detailed their results with the nasal test.

The researchers collected 31 nasal samples from patients with sporadic CJD and 43 samples from patients who had other neurologic diseases or no neurologic disease. The team brushed the inside of a subject’s nose to collect olfactory neurons connected to the brain.

Testing these samples allowed the researchers to correctly identify 30 of the 31 sporadic CJD patients (97% sensitivity). The tests also correctly showed negative results for all 43 of the non-CJD patients (100% specificity).

By comparison, tests using cerebral spinal fluid, which is currently used to detect sporadic CJD, were 77% sensitive and 100% specific. And these results took twice as long to obtain.

While continuing to validate the new testing method in CJD patients, the scientists are looking to expand their research to diagnose forms of prion diseases in sheep, cattle, and wildlife. The team also hopes to replace the nasal brush with an even simpler swabbing approach.

Urine test for variant CJD

In another NEJM article, Fabio Moda, PhD, of the University of Texas Medical School at Houston, and his colleagues described results observed with their urine test.

The team noted that the infectious agent in transmissible spongiform encephalopathies appears to be composed exclusively of the misfolded form of the prion protein, PrP^Sc. So they set out to determine if they could detect PrP^Sc in the urine of patients with CJD.

The researchers analyzed urine samples from healthy individuals (n=52) and patients with variant CJD (n=68), sporadic CJD (n=14), genetic forms of prion disease (n=4), other neurodegenerative disorders (n=50), and nondegenerative neurologic disorders (n=50).

The group found they could only detect PrP^Sc in samples from patients with variant CJD. They found “minute quantities” of PrP^Sc in 13 of the 14 urine samples from variant CJD patients, but PrP^Sc was not present in any of the samples from the other patients or the healthy individuals.

This suggests the test has a sensitivity of 92.9% and a specificity of 100%.

Blood for transfusion

Credit: Elise Amendola

Two groups of scientists have developed new tests to diagnose Creutzfeldt-Jakob disease (CJD).

One test uses samples collected from nasal passages to detect sporadic CJD, and the other uses urine samples to identify variant CJD.

The researchers said these tests provide simple methods for differentiating CJD from other diseases and could help prevent the transmission of CJD via blood

transfusions, transplants, or contaminated surgical instruments.

Both tests are described in The New England Journal of Medicine.

Nasal test for sporadic CJD

In one NEJM article, Byron Caughey, PhD, of the National Institute of Allergy and Infectious Diseases in Rockville, Maryland, and his colleagues detailed their results with the nasal test.

The researchers collected 31 nasal samples from patients with sporadic CJD and 43 samples from patients who had other neurologic diseases or no neurologic disease. The team brushed the inside of a subject’s nose to collect olfactory neurons connected to the brain.

Testing these samples allowed the researchers to correctly identify 30 of the 31 sporadic CJD patients (97% sensitivity). The tests also correctly showed negative results for all 43 of the non-CJD patients (100% specificity).

By comparison, tests using cerebral spinal fluid, which is currently used to detect sporadic CJD, were 77% sensitive and 100% specific. And these results took twice as long to obtain.

While continuing to validate the new testing method in CJD patients, the scientists are looking to expand their research to diagnose forms of prion diseases in sheep, cattle, and wildlife. The team also hopes to replace the nasal brush with an even simpler swabbing approach.

Urine test for variant CJD

In another NEJM article, Fabio Moda, PhD, of the University of Texas Medical School at Houston, and his colleagues described results observed with their urine test.

The team noted that the infectious agent in transmissible spongiform encephalopathies appears to be composed exclusively of the misfolded form of the prion protein, PrP^Sc. So they set out to determine if they could detect PrP^Sc in the urine of patients with CJD.

The researchers analyzed urine samples from healthy individuals (n=52) and patients with variant CJD (n=68), sporadic CJD (n=14), genetic forms of prion disease (n=4), other neurodegenerative disorders (n=50), and nondegenerative neurologic disorders (n=50).

The group found they could only detect PrP^Sc in samples from patients with variant CJD. They found “minute quantities” of PrP^Sc in 13 of the 14 urine samples from variant CJD patients, but PrP^Sc was not present in any of the samples from the other patients or the healthy individuals.

This suggests the test has a sensitivity of 92.9% and a specificity of 100%.

Blood for transfusion

Credit: Elise Amendola

Two groups of scientists have developed new tests to diagnose Creutzfeldt-Jakob disease (CJD).

One test uses samples collected from nasal passages to detect sporadic CJD, and the other uses urine samples to identify variant CJD.

The researchers said these tests provide simple methods for differentiating CJD from other diseases and could help prevent the transmission of CJD via blood

transfusions, transplants, or contaminated surgical instruments.

Both tests are described in The New England Journal of Medicine.

Nasal test for sporadic CJD

In one NEJM article, Byron Caughey, PhD, of the National Institute of Allergy and Infectious Diseases in Rockville, Maryland, and his colleagues detailed their results with the nasal test.

The researchers collected 31 nasal samples from patients with sporadic CJD and 43 samples from patients who had other neurologic diseases or no neurologic disease. The team brushed the inside of a subject’s nose to collect olfactory neurons connected to the brain.

Testing these samples allowed the researchers to correctly identify 30 of the 31 sporadic CJD patients (97% sensitivity). The tests also correctly showed negative results for all 43 of the non-CJD patients (100% specificity).

By comparison, tests using cerebral spinal fluid, which is currently used to detect sporadic CJD, were 77% sensitive and 100% specific. And these results took twice as long to obtain.

While continuing to validate the new testing method in CJD patients, the scientists are looking to expand their research to diagnose forms of prion diseases in sheep, cattle, and wildlife. The team also hopes to replace the nasal brush with an even simpler swabbing approach.

Urine test for variant CJD

In another NEJM article, Fabio Moda, PhD, of the University of Texas Medical School at Houston, and his colleagues described results observed with their urine test.

The team noted that the infectious agent in transmissible spongiform encephalopathies appears to be composed exclusively of the misfolded form of the prion protein, PrP^Sc. So they set out to determine if they could detect PrP^Sc in the urine of patients with CJD.

The researchers analyzed urine samples from healthy individuals (n=52) and patients with variant CJD (n=68), sporadic CJD (n=14), genetic forms of prion disease (n=4), other neurodegenerative disorders (n=50), and nondegenerative neurologic disorders (n=50).

The group found they could only detect PrP^Sc in samples from patients with variant CJD. They found “minute quantities” of PrP^Sc in 13 of the 14 urine samples from variant CJD patients, but PrP^Sc was not present in any of the samples from the other patients or the healthy individuals.

This suggests the test has a sensitivity of 92.9% and a specificity of 100%.

Lab mouse

Results of a new study contradict previous research suggesting mice do not make suitable models for human inflammatory conditions.

The original study, published in PNAS in February 2013, indicated that genomic responses to different acute inflammatory stressors—trauma, burns, sepsis, and infection—are highly similar in humans but poorly reproduced in corresponding mouse models.

The new study, published in PNAS yesterday, suggests that is not the case.

The original study was conducted by Junhee Seok, PhD, of Northwestern University, and his colleagues. It garnered a lot of attention from the scientific community and the general public, reigniting the debate over mouse models’ suitability for medical research.

Tsuyoshi Miyakawa, PhD, of Fujita Health University in Japan, was among those who argued that mice are suitable models, and Dr Seok’s findings were likely incorrect.

So Dr Miyakawa and his colleague, Keizo Takao, PhD, of the National Institute for Physiological Sciences in Japan, reanalyzed the data from Dr Seok’s study using the bioinformatics tool NextBio. 

Dr Seok’s group had compared the expression levels of genes that were altered in a particular human condition between humans and mice.

A comparison of the genomic response between humans and mice, including those genes altered in one species but not in another, obscures the correlation between homologous genes of humans and mice to nearly 0, as the team showed.

The group’s comparison of the gene expression patterns between human burn victims and mouse models of burns, trauma, sepsis, and infection revealed a Pearson’s correlation coefficient (R) that ranged from 0.14 to 0.28. And the percentage of genes whose expression changed in the same direction was 55% to 61%.

In the new analysis based on the same data, Drs Miyakawa and Takao found the R values ranged from 0.36 to 0.59. And 77% to 93% of the genes changed in the same directions between the human condition and the mouse models.

Non-parametric ranking analysis using NextBio showed the pattern of the gene expression changes in mouse models was highly similar to that in human burn conditions—a significant correlation (P = 6.5 x 10^-11 to 1.2 x 10^-35).

Drs Miyakawa and Takao noted that many molecular pathways are commonly dysregulated in human diseases and mouse models. And focusing on the commonalities between human diseases and mouse models will allow us to derive useful information for studying the pathophysiology and pathogenesis of human diseases, as well as aid treatment development.

Lab mouse

Results of a new study contradict previous research suggesting mice do not make suitable models for human inflammatory conditions.

The original study, published in PNAS in February 2013, indicated that genomic responses to different acute inflammatory stressors—trauma, burns, sepsis, and infection—are highly similar in humans but poorly reproduced in corresponding mouse models.

The new study, published in PNAS yesterday, suggests that is not the case.

The original study was conducted by Junhee Seok, PhD, of Northwestern University, and his colleagues. It garnered a lot of attention from the scientific community and the general public, reigniting the debate over mouse models’ suitability for medical research.

Tsuyoshi Miyakawa, PhD, of Fujita Health University in Japan, was among those who argued that mice are suitable models, and Dr Seok’s findings were likely incorrect.

So Dr Miyakawa and his colleague, Keizo Takao, PhD, of the National Institute for Physiological Sciences in Japan, reanalyzed the data from Dr Seok’s study using the bioinformatics tool NextBio. 

Dr Seok’s group had compared the expression levels of genes that were altered in a particular human condition between humans and mice.

A comparison of the genomic response between humans and mice, including those genes altered in one species but not in another, obscures the correlation between homologous genes of humans and mice to nearly 0, as the team showed.

The group’s comparison of the gene expression patterns between human burn victims and mouse models of burns, trauma, sepsis, and infection revealed a Pearson’s correlation coefficient (R) that ranged from 0.14 to 0.28. And the percentage of genes whose expression changed in the same direction was 55% to 61%.

In the new analysis based on the same data, Drs Miyakawa and Takao found the R values ranged from 0.36 to 0.59. And 77% to 93% of the genes changed in the same directions between the human condition and the mouse models.

Non-parametric ranking analysis using NextBio showed the pattern of the gene expression changes in mouse models was highly similar to that in human burn conditions—a significant correlation (P = 6.5 x 10^-11 to 1.2 x 10^-35).

Drs Miyakawa and Takao noted that many molecular pathways are commonly dysregulated in human diseases and mouse models. And focusing on the commonalities between human diseases and mouse models will allow us to derive useful information for studying the pathophysiology and pathogenesis of human diseases, as well as aid treatment development.

Lab mouse

Results of a new study contradict previous research suggesting mice do not make suitable models for human inflammatory conditions.

The original study, published in PNAS in February 2013, indicated that genomic responses to different acute inflammatory stressors—trauma, burns, sepsis, and infection—are highly similar in humans but poorly reproduced in corresponding mouse models.

The new study, published in PNAS yesterday, suggests that is not the case.

The original study was conducted by Junhee Seok, PhD, of Northwestern University, and his colleagues. It garnered a lot of attention from the scientific community and the general public, reigniting the debate over mouse models’ suitability for medical research.

Tsuyoshi Miyakawa, PhD, of Fujita Health University in Japan, was among those who argued that mice are suitable models, and Dr Seok’s findings were likely incorrect.

So Dr Miyakawa and his colleague, Keizo Takao, PhD, of the National Institute for Physiological Sciences in Japan, reanalyzed the data from Dr Seok’s study using the bioinformatics tool NextBio. 

Dr Seok’s group had compared the expression levels of genes that were altered in a particular human condition between humans and mice.

A comparison of the genomic response between humans and mice, including those genes altered in one species but not in another, obscures the correlation between homologous genes of humans and mice to nearly 0, as the team showed.

The group’s comparison of the gene expression patterns between human burn victims and mouse models of burns, trauma, sepsis, and infection revealed a Pearson’s correlation coefficient (R) that ranged from 0.14 to 0.28. And the percentage of genes whose expression changed in the same direction was 55% to 61%.

In the new analysis based on the same data, Drs Miyakawa and Takao found the R values ranged from 0.36 to 0.59. And 77% to 93% of the genes changed in the same directions between the human condition and the mouse models.

Non-parametric ranking analysis using NextBio showed the pattern of the gene expression changes in mouse models was highly similar to that in human burn conditions—a significant correlation (P = 6.5 x 10^-11 to 1.2 x 10^-35).

Drs Miyakawa and Takao noted that many molecular pathways are commonly dysregulated in human diseases and mouse models. And focusing on the commonalities between human diseases and mouse models will allow us to derive useful information for studying the pathophysiology and pathogenesis of human diseases, as well as aid treatment development.

Blood in bags and vials

Credit: Daniel Gay

Roughly 1 in 3000 English blood donors have hepatitis E virus (HEV) in their plasma, according to research published in The Lancet.

This suggests that about 1200 HEV-containing blood components may be transfused in England every year.

“HEV genotype 3 infections are widespread in the English population, including blood donors,” said study author Richard Tedder, MB ChB, of National Health Service Blood and Transplant in London.

“We estimate that between 80,000 and 100,000 human HEV infections are likely to have occurred in England during the year of our study.”

These figures seem to indicate a need for screening blood donations. But Dr Tedder and his colleagues found evidence suggesting a low overall burden of harm from transfusion-transmitted HEV.

The researchers retrospectively screened 225,000 individual blood donations collected in south east England between October 2012 and September 2013 for HEV RNA.

Seventy-nine donors—about 1 in 2848—were infected with genotype 3 HEV, which can spread directly from animals to humans. The 79 donations had been used to prepare 129 blood components, 62 of which had been transfused.

Follow-up of 43 exposed recipients showed that transmission had occurred in 18 (42%) patients.

Immunosuppression extended the duration of viremia in these patients, but 3 cleared their infection following a change in immunosuppressive therapy or after receiving ribavirin.

Ten of the patients developed prolonged or persistent infection. Transaminitis was common, and 1 patient developed hepatitis.

“Although rarely causing any acute illness, hepatitis E infections may become persistent in immunosuppressed patients, putting them at risk of future chronic liver disease, and a policy is needed to identify these persistently infected patients and provide them with appropriate antiviral treatment,” Dr Tedder said.

“However, our study indicates that the overall burden of harm resulting from transfusion-transmitted HEV is slight. Although, on a clinical basis alone, there appears no pressing need at this time for blood donations to be screened, a broader discussion over harm mitigation is now required.”

A related comment article in The Lancet suggested there is, in fact, a need for the systematic screening of blood components.

“The potential clinical results of blood-borne HEV infection should not be downplayed; in particular, the risk of serious complications and death exists,” wrote Jean-Michel Pawlotsky, MD, PhD, of Hôpital Henri Mondor in Créteil, France.

“Thus, on the basis of [the current] and other studies, I believe that systematic screening of blood components for markers of hepatitis E infection should be implemented in areas where HEV is endemic (eg, the European Union), based on HEV RNA detection.”

Blood in bags and vials

Credit: Daniel Gay

Roughly 1 in 3000 English blood donors have hepatitis E virus (HEV) in their plasma, according to research published in The Lancet.

This suggests that about 1200 HEV-containing blood components may be transfused in England every year.

“HEV genotype 3 infections are widespread in the English population, including blood donors,” said study author Richard Tedder, MB ChB, of National Health Service Blood and Transplant in London.

“We estimate that between 80,000 and 100,000 human HEV infections are likely to have occurred in England during the year of our study.”

These figures seem to indicate a need for screening blood donations. But Dr Tedder and his colleagues found evidence suggesting a low overall burden of harm from transfusion-transmitted HEV.

The researchers retrospectively screened 225,000 individual blood donations collected in south east England between October 2012 and September 2013 for HEV RNA.

Seventy-nine donors—about 1 in 2848—were infected with genotype 3 HEV, which can spread directly from animals to humans. The 79 donations had been used to prepare 129 blood components, 62 of which had been transfused.

Follow-up of 43 exposed recipients showed that transmission had occurred in 18 (42%) patients.

Immunosuppression extended the duration of viremia in these patients, but 3 cleared their infection following a change in immunosuppressive therapy or after receiving ribavirin.

Ten of the patients developed prolonged or persistent infection. Transaminitis was common, and 1 patient developed hepatitis.

“Although rarely causing any acute illness, hepatitis E infections may become persistent in immunosuppressed patients, putting them at risk of future chronic liver disease, and a policy is needed to identify these persistently infected patients and provide them with appropriate antiviral treatment,” Dr Tedder said.

“However, our study indicates that the overall burden of harm resulting from transfusion-transmitted HEV is slight. Although, on a clinical basis alone, there appears no pressing need at this time for blood donations to be screened, a broader discussion over harm mitigation is now required.”

A related comment article in The Lancet suggested there is, in fact, a need for the systematic screening of blood components.

“The potential clinical results of blood-borne HEV infection should not be downplayed; in particular, the risk of serious complications and death exists,” wrote Jean-Michel Pawlotsky, MD, PhD, of Hôpital Henri Mondor in Créteil, France.

“Thus, on the basis of [the current] and other studies, I believe that systematic screening of blood components for markers of hepatitis E infection should be implemented in areas where HEV is endemic (eg, the European Union), based on HEV RNA detection.”

Blood in bags and vials

Credit: Daniel Gay

Roughly 1 in 3000 English blood donors have hepatitis E virus (HEV) in their plasma, according to research published in The Lancet.

This suggests that about 1200 HEV-containing blood components may be transfused in England every year.

“HEV genotype 3 infections are widespread in the English population, including blood donors,” said study author Richard Tedder, MB ChB, of National Health Service Blood and Transplant in London.

“We estimate that between 80,000 and 100,000 human HEV infections are likely to have occurred in England during the year of our study.”

These figures seem to indicate a need for screening blood donations. But Dr Tedder and his colleagues found evidence suggesting a low overall burden of harm from transfusion-transmitted HEV.

The researchers retrospectively screened 225,000 individual blood donations collected in south east England between October 2012 and September 2013 for HEV RNA.

Seventy-nine donors—about 1 in 2848—were infected with genotype 3 HEV, which can spread directly from animals to humans. The 79 donations had been used to prepare 129 blood components, 62 of which had been transfused.

Follow-up of 43 exposed recipients showed that transmission had occurred in 18 (42%) patients.

Immunosuppression extended the duration of viremia in these patients, but 3 cleared their infection following a change in immunosuppressive therapy or after receiving ribavirin.

Ten of the patients developed prolonged or persistent infection. Transaminitis was common, and 1 patient developed hepatitis.

“Although rarely causing any acute illness, hepatitis E infections may become persistent in immunosuppressed patients, putting them at risk of future chronic liver disease, and a policy is needed to identify these persistently infected patients and provide them with appropriate antiviral treatment,” Dr Tedder said.

“However, our study indicates that the overall burden of harm resulting from transfusion-transmitted HEV is slight. Although, on a clinical basis alone, there appears no pressing need at this time for blood donations to be screened, a broader discussion over harm mitigation is now required.”

A related comment article in The Lancet suggested there is, in fact, a need for the systematic screening of blood components.

“The potential clinical results of blood-borne HEV infection should not be downplayed; in particular, the risk of serious complications and death exists,” wrote Jean-Michel Pawlotsky, MD, PhD, of Hôpital Henri Mondor in Créteil, France.

“Thus, on the basis of [the current] and other studies, I believe that systematic screening of blood components for markers of hepatitis E infection should be implemented in areas where HEV is endemic (eg, the European Union), based on HEV RNA detection.”

Blood for transfusion

Credit: UAB Hospital

A change in transfusion protocol has resulted in fewer potentially preventable deaths among soldiers, researchers have reported in JAMA Surgery.

In 2006, hospitals treating soldiers from Iraq and Afghanistan implemented a protocol called damage control resuscitation (DCR).

It involves administering blood products early and in a balanced ratio, using an aggressive approach to correct coagulopathy, and minimizing the use of crystalloid fluids.

The research showed that soldiers who died in the hospital after DCR was implemented were more likely than their predecessors to be severely injured and have a severe brain injury.

And this is consistent with a decrease in potentially preventable deaths, according to study author Nicholas R. Langan, MD, of the Madigan Army Medical Center in Tacoma, Washington, and his colleagues.

To conduct the study, the researchers reviewed data from the Joint Theater Trauma Registry of US forward combat hospitals. This included 57,179 soldiers, 2565 (4.5%) of whom died in the hospital. Seventy-four percent of these patients were severely injured, and 80% died within 24 hours of admission.

To assess the impact of DCR, the researchers divided patients into 2 groups: those treated before DCR implementation, from 2002 through 2005, and those treated with the DCR protocol, from 2006 through 2011.

The analysis showed that DCR policies were successfully implemented. There was a significant decrease in mean crystalloid infusion volume in the first 24 hours after hospitalization, from 6.1 L to 3.2 L (P<0.05).

There was a significant increase in fresh-frozen plasma use—from 3.2 U to 10.1 U (P=0.01)—and packed red blood cell use—from 8.4 U to 11.4 U (P=0.01)—in the first 24 hours after hospitalization.

And the mean ratio of packed red blood cells to fresh-frozen plasma changed from 2.6:1 in the pre-DCR period to 1.4:1 during the DCR period (P<0.01).

On the other hand, there was no significant difference in cryoprecipitate use, platelet use, or the ratio of packed red blood cells to cryoprecipitate or platelets.

The change in treatment protocol was associated with a change in the incidence of early and late, but not intermediate, deaths. The incidence of early death (within the first 24 hours) increased from 77% pre-DCR to 80% during DCR (P=0.02).

The incidence of late death (more than 7 days after injury) decreased from 10% pre-DCR to 6% during DCR (P<0.01). And the rate of intermediate death (1-7 days after injury) measured 13% for both periods (P=0.95).

The percentage of patients with any severe injury increased significantly from the pre-DCR period to the DCR period, from 64% to 80% (P<0.05). And the percentage of patients with severe head injuries increased significantly, from 57% to 73% (P<0.05).

As patients who died during the DCR period were more likely to have such “nonsurvivable” wounds, the researchers said this suggests that DCR is associated with a decrease in deaths among potentially salvageable patients.

Blood for transfusion

Credit: UAB Hospital

A change in transfusion protocol has resulted in fewer potentially preventable deaths among soldiers, researchers have reported in JAMA Surgery.

In 2006, hospitals treating soldiers from Iraq and Afghanistan implemented a protocol called damage control resuscitation (DCR).

It involves administering blood products early and in a balanced ratio, using an aggressive approach to correct coagulopathy, and minimizing the use of crystalloid fluids.

The research showed that soldiers who died in the hospital after DCR was implemented were more likely than their predecessors to be severely injured and have a severe brain injury.

And this is consistent with a decrease in potentially preventable deaths, according to study author Nicholas R. Langan, MD, of the Madigan Army Medical Center in Tacoma, Washington, and his colleagues.

To conduct the study, the researchers reviewed data from the Joint Theater Trauma Registry of US forward combat hospitals. This included 57,179 soldiers, 2565 (4.5%) of whom died in the hospital. Seventy-four percent of these patients were severely injured, and 80% died within 24 hours of admission.

To assess the impact of DCR, the researchers divided patients into 2 groups: those treated before DCR implementation, from 2002 through 2005, and those treated with the DCR protocol, from 2006 through 2011.

The analysis showed that DCR policies were successfully implemented. There was a significant decrease in mean crystalloid infusion volume in the first 24 hours after hospitalization, from 6.1 L to 3.2 L (P<0.05).

There was a significant increase in fresh-frozen plasma use—from 3.2 U to 10.1 U (P=0.01)—and packed red blood cell use—from 8.4 U to 11.4 U (P=0.01)—in the first 24 hours after hospitalization.

And the mean ratio of packed red blood cells to fresh-frozen plasma changed from 2.6:1 in the pre-DCR period to 1.4:1 during the DCR period (P<0.01).

On the other hand, there was no significant difference in cryoprecipitate use, platelet use, or the ratio of packed red blood cells to cryoprecipitate or platelets.

The change in treatment protocol was associated with a change in the incidence of early and late, but not intermediate, deaths. The incidence of early death (within the first 24 hours) increased from 77% pre-DCR to 80% during DCR (P=0.02).

The incidence of late death (more than 7 days after injury) decreased from 10% pre-DCR to 6% during DCR (P<0.01). And the rate of intermediate death (1-7 days after injury) measured 13% for both periods (P=0.95).

The percentage of patients with any severe injury increased significantly from the pre-DCR period to the DCR period, from 64% to 80% (P<0.05). And the percentage of patients with severe head injuries increased significantly, from 57% to 73% (P<0.05).

As patients who died during the DCR period were more likely to have such “nonsurvivable” wounds, the researchers said this suggests that DCR is associated with a decrease in deaths among potentially salvageable patients.

Blood for transfusion

Credit: UAB Hospital

A change in transfusion protocol has resulted in fewer potentially preventable deaths among soldiers, researchers have reported in JAMA Surgery.

In 2006, hospitals treating soldiers from Iraq and Afghanistan implemented a protocol called damage control resuscitation (DCR).

It involves administering blood products early and in a balanced ratio, using an aggressive approach to correct coagulopathy, and minimizing the use of crystalloid fluids.

The research showed that soldiers who died in the hospital after DCR was implemented were more likely than their predecessors to be severely injured and have a severe brain injury.

And this is consistent with a decrease in potentially preventable deaths, according to study author Nicholas R. Langan, MD, of the Madigan Army Medical Center in Tacoma, Washington, and his colleagues.

To conduct the study, the researchers reviewed data from the Joint Theater Trauma Registry of US forward combat hospitals. This included 57,179 soldiers, 2565 (4.5%) of whom died in the hospital. Seventy-four percent of these patients were severely injured, and 80% died within 24 hours of admission.

To assess the impact of DCR, the researchers divided patients into 2 groups: those treated before DCR implementation, from 2002 through 2005, and those treated with the DCR protocol, from 2006 through 2011.

The analysis showed that DCR policies were successfully implemented. There was a significant decrease in mean crystalloid infusion volume in the first 24 hours after hospitalization, from 6.1 L to 3.2 L (P<0.05).

There was a significant increase in fresh-frozen plasma use—from 3.2 U to 10.1 U (P=0.01)—and packed red blood cell use—from 8.4 U to 11.4 U (P=0.01)—in the first 24 hours after hospitalization.

And the mean ratio of packed red blood cells to fresh-frozen plasma changed from 2.6:1 in the pre-DCR period to 1.4:1 during the DCR period (P<0.01).

On the other hand, there was no significant difference in cryoprecipitate use, platelet use, or the ratio of packed red blood cells to cryoprecipitate or platelets.

The change in treatment protocol was associated with a change in the incidence of early and late, but not intermediate, deaths. The incidence of early death (within the first 24 hours) increased from 77% pre-DCR to 80% during DCR (P=0.02).

The incidence of late death (more than 7 days after injury) decreased from 10% pre-DCR to 6% during DCR (P<0.01). And the rate of intermediate death (1-7 days after injury) measured 13% for both periods (P=0.95).

The percentage of patients with any severe injury increased significantly from the pre-DCR period to the DCR period, from 64% to 80% (P<0.05). And the percentage of patients with severe head injuries increased significantly, from 57% to 73% (P<0.05).

As patients who died during the DCR period were more likely to have such “nonsurvivable” wounds, the researchers said this suggests that DCR is associated with a decrease in deaths among potentially salvageable patients.

Platelets (blue) in a thrombus

Credit: Andre E.X. Brown

A next-generation bioreactor can produce fully functional platelets, according to research published in Blood.

The bioreactor recapitulates human bone marrow and blood vessel microenvironments.

And when the researchers introduced megakaryocytes derived from human induced pluripotent stem cell cultures (hiPSC-MKs), the bioreactor produced platelets with the structural and functional properties of natural platelets.

The team said this work is a major advancement that could help address blood transfusion needs worldwide.

“The ability to generate an alternative source of functional human platelets with virtually no disease transmission represents a paradigm shift in how we collect platelets that may allow us to meet the growing need for blood transfusions,” said lead study author Jonathan Thon, PhD, of Brigham and Women’s Hospital in Boston.

His group’s bioreactor uses biologically inspired engineering to fully integrate the major components of bone marrow, modeling both its composition and blood flow characteristics.

The bioreactor recapitulates features such as bone marrow stiffness, extracellular matrix composition, micro-channel size, and blood flow stability under high-resolution live-cell microscopy to make human platelets.

“[B]eing able to develop a device that successfully models bone marrow represents a crucial bridge connecting our understanding of the physiological triggers of platelet formation to support drug development and scale platelet production,” said senior study author Joseph Italiano, Jr, PhD, also of Brigham and Women’s Hospital.

He and his colleagues showed that physiological shear stresses in the bioreactor triggered proplatelet initiation, reproduced ex vivo bone marrow proplatelet production, and generated functional platelets.

In static culture, hiPSC-MKs began producing proplatelets at 6 hours post-isolation and reached maximal production at 18 hours. However, hiPSC-MKs under physiological shear stress began producing proplatelets immediately upon trapping and extended/released proplatelets within the first 2 hours of culture.

About 90% of hiPSC-MKs under shear stress produced proplatelets, compared to 10% of hiPSC-MKs in static cultures.

The hiPSC-MK-derived bioreactor platelets displayed forward scatter, side scatter, and surface biomarker expression characteristic of human platelets. Electron microscopy showed the 2 types of platelets were ultrastructurally indistinguishable from one another.

Furthermore, bioreactor platelets displayed morphology and microtubule expression comparable to human platelets. And bioreactor platelets spread normally upon contact-activation with glass, forming both filpodia and lamellipodia.

“Bioreactor-derived platelets theoretically have several advantages over conventional, donor-derived platelets in terms of safety and resource utilization,” said William Savage, MD, PhD, medical director at Kraft Family Blood Donor Center at Brigham and Women’s Hospital, who did not contribute to the study.

“A major factor that has limited our ability to compare bioreactor platelets to donor platelets is the inefficiency of growing platelets, a problem that slows progress of clinical research. This study addresses that gap, while contributing to our understanding of platelet biology at the same time.”

Based on the promising results of this study, the researchers would like to begin clinical trials testing the bioreactor platelets in 2017.

“The regulatory bar is appropriately set high for blood products,” Dr Thon said. “And it is important to us that we show platelet quality, function, and safety over these next 3 years, since we’ll likely be recipients of these platelets ourselves at some point.”

Platelets (blue) in a thrombus

Credit: Andre E.X. Brown

A next-generation bioreactor can produce fully functional platelets, according to research published in Blood.

The bioreactor recapitulates human bone marrow and blood vessel microenvironments.

And when the researchers introduced megakaryocytes derived from human induced pluripotent stem cell cultures (hiPSC-MKs), the bioreactor produced platelets with the structural and functional properties of natural platelets.

The team said this work is a major advancement that could help address blood transfusion needs worldwide.

“The ability to generate an alternative source of functional human platelets with virtually no disease transmission represents a paradigm shift in how we collect platelets that may allow us to meet the growing need for blood transfusions,” said lead study author Jonathan Thon, PhD, of Brigham and Women’s Hospital in Boston.

His group’s bioreactor uses biologically inspired engineering to fully integrate the major components of bone marrow, modeling both its composition and blood flow characteristics.

The bioreactor recapitulates features such as bone marrow stiffness, extracellular matrix composition, micro-channel size, and blood flow stability under high-resolution live-cell microscopy to make human platelets.

“[B]eing able to develop a device that successfully models bone marrow represents a crucial bridge connecting our understanding of the physiological triggers of platelet formation to support drug development and scale platelet production,” said senior study author Joseph Italiano, Jr, PhD, also of Brigham and Women’s Hospital.

He and his colleagues showed that physiological shear stresses in the bioreactor triggered proplatelet initiation, reproduced ex vivo bone marrow proplatelet production, and generated functional platelets.

In static culture, hiPSC-MKs began producing proplatelets at 6 hours post-isolation and reached maximal production at 18 hours. However, hiPSC-MKs under physiological shear stress began producing proplatelets immediately upon trapping and extended/released proplatelets within the first 2 hours of culture.

About 90% of hiPSC-MKs under shear stress produced proplatelets, compared to 10% of hiPSC-MKs in static cultures.

The hiPSC-MK-derived bioreactor platelets displayed forward scatter, side scatter, and surface biomarker expression characteristic of human platelets. Electron microscopy showed the 2 types of platelets were ultrastructurally indistinguishable from one another.

Furthermore, bioreactor platelets displayed morphology and microtubule expression comparable to human platelets. And bioreactor platelets spread normally upon contact-activation with glass, forming both filpodia and lamellipodia.

“Bioreactor-derived platelets theoretically have several advantages over conventional, donor-derived platelets in terms of safety and resource utilization,” said William Savage, MD, PhD, medical director at Kraft Family Blood Donor Center at Brigham and Women’s Hospital, who did not contribute to the study.

“A major factor that has limited our ability to compare bioreactor platelets to donor platelets is the inefficiency of growing platelets, a problem that slows progress of clinical research. This study addresses that gap, while contributing to our understanding of platelet biology at the same time.”

Based on the promising results of this study, the researchers would like to begin clinical trials testing the bioreactor platelets in 2017.

“The regulatory bar is appropriately set high for blood products,” Dr Thon said. “And it is important to us that we show platelet quality, function, and safety over these next 3 years, since we’ll likely be recipients of these platelets ourselves at some point.”

Platelets (blue) in a thrombus

Credit: Andre E.X. Brown

A next-generation bioreactor can produce fully functional platelets, according to research published in Blood.

The bioreactor recapitulates human bone marrow and blood vessel microenvironments.

And when the researchers introduced megakaryocytes derived from human induced pluripotent stem cell cultures (hiPSC-MKs), the bioreactor produced platelets with the structural and functional properties of natural platelets.

The team said this work is a major advancement that could help address blood transfusion needs worldwide.

“The ability to generate an alternative source of functional human platelets with virtually no disease transmission represents a paradigm shift in how we collect platelets that may allow us to meet the growing need for blood transfusions,” said lead study author Jonathan Thon, PhD, of Brigham and Women’s Hospital in Boston.

His group’s bioreactor uses biologically inspired engineering to fully integrate the major components of bone marrow, modeling both its composition and blood flow characteristics.

The bioreactor recapitulates features such as bone marrow stiffness, extracellular matrix composition, micro-channel size, and blood flow stability under high-resolution live-cell microscopy to make human platelets.

“[B]eing able to develop a device that successfully models bone marrow represents a crucial bridge connecting our understanding of the physiological triggers of platelet formation to support drug development and scale platelet production,” said senior study author Joseph Italiano, Jr, PhD, also of Brigham and Women’s Hospital.

He and his colleagues showed that physiological shear stresses in the bioreactor triggered proplatelet initiation, reproduced ex vivo bone marrow proplatelet production, and generated functional platelets.

In static culture, hiPSC-MKs began producing proplatelets at 6 hours post-isolation and reached maximal production at 18 hours. However, hiPSC-MKs under physiological shear stress began producing proplatelets immediately upon trapping and extended/released proplatelets within the first 2 hours of culture.

About 90% of hiPSC-MKs under shear stress produced proplatelets, compared to 10% of hiPSC-MKs in static cultures.

The hiPSC-MK-derived bioreactor platelets displayed forward scatter, side scatter, and surface biomarker expression characteristic of human platelets. Electron microscopy showed the 2 types of platelets were ultrastructurally indistinguishable from one another.

Furthermore, bioreactor platelets displayed morphology and microtubule expression comparable to human platelets. And bioreactor platelets spread normally upon contact-activation with glass, forming both filpodia and lamellipodia.

“Bioreactor-derived platelets theoretically have several advantages over conventional, donor-derived platelets in terms of safety and resource utilization,” said William Savage, MD, PhD, medical director at Kraft Family Blood Donor Center at Brigham and Women’s Hospital, who did not contribute to the study.

“A major factor that has limited our ability to compare bioreactor platelets to donor platelets is the inefficiency of growing platelets, a problem that slows progress of clinical research. This study addresses that gap, while contributing to our understanding of platelet biology at the same time.”

Based on the promising results of this study, the researchers would like to begin clinical trials testing the bioreactor platelets in 2017.

“The regulatory bar is appropriately set high for blood products,” Dr Thon said. “And it is important to us that we show platelet quality, function, and safety over these next 3 years, since we’ll likely be recipients of these platelets ourselves at some point.”

Transcription factors prompt

stem cells to form endothelium

(green), then blood cells (red)

Credit: Irina Elcheva

and Akhilesh Kumar

Researchers have reported a new method for creating human blood cells in the lab, and they believe the approach is safer and more reliable than its predecessors.

The team determined how blood cells are made at the earliest stages of development; namely, 2 genetic programs are responsible for turning pluripotent stem cells into blood cells.

This discovery gave the researchers the tools to make an array of blood cells themselves, using transcription factors.

“This is the first demonstration of the production of different kinds of cells from human pluripotent stem cells using transcription factors,” said Igor Slukvin, MD, PhD, of the University of Wisconsin-Madison.

He and his colleagues described this method in Nature Communications.

During development, blood cells emerge in the aorta. There, blood cells, including hematopoietic stem cells, are generated by budding from hemogenic endothelial cells.

Dr Slukvin and his colleagues found that 2 distinct groups of transcription factors—pan-myeloid (ETV2 and GATA2) and erythro-megakaryocytic (GATA2 and TAL1)—directly convert human pluripotent stem cells into hemogenic endothelial cells.

These cells then develop into blood cells with pan-myeloid or erythro-megakaryocytic potential.

“By overexpressing just 2 transcription factors, we can, in the laboratory dish, reproduce the sequence of events we see in the embryo,” Dr Slukvin said.

Furthermore, the method could produce blood cells in abundance. For every million stem cells, the researchers were able to produce 30 million blood cells.

The team noted that a critical aspect of this work is the use of modified messenger RNA to direct stem cells toward particular developmental fates.

This approach makes it possible to induce cells without introducing any genetic artifacts. So this method of blood cell production is safer than other methods, according to the researchers.

“You can do it without a virus, and genome integrity is not affected,” Dr Slukvin noted.

He added that his group is still working on a method for producing hematopoietic stem cells in the lab.

“We still don’t know how to do that,” he said. “But our new approach to making blood cells will give us an opportunity to model their development in a dish and identify novel hematopoietic stem cell factors.”

Transcription factors prompt

stem cells to form endothelium

(green), then blood cells (red)

Credit: Irina Elcheva

and Akhilesh Kumar

Researchers have reported a new method for creating human blood cells in the lab, and they believe the approach is safer and more reliable than its predecessors.

The team determined how blood cells are made at the earliest stages of development; namely, 2 genetic programs are responsible for turning pluripotent stem cells into blood cells.

This discovery gave the researchers the tools to make an array of blood cells themselves, using transcription factors.

“This is the first demonstration of the production of different kinds of cells from human pluripotent stem cells using transcription factors,” said Igor Slukvin, MD, PhD, of the University of Wisconsin-Madison.

He and his colleagues described this method in Nature Communications.

During development, blood cells emerge in the aorta. There, blood cells, including hematopoietic stem cells, are generated by budding from hemogenic endothelial cells.

Dr Slukvin and his colleagues found that 2 distinct groups of transcription factors—pan-myeloid (ETV2 and GATA2) and erythro-megakaryocytic (GATA2 and TAL1)—directly convert human pluripotent stem cells into hemogenic endothelial cells.

These cells then develop into blood cells with pan-myeloid or erythro-megakaryocytic potential.

“By overexpressing just 2 transcription factors, we can, in the laboratory dish, reproduce the sequence of events we see in the embryo,” Dr Slukvin said.

Furthermore, the method could produce blood cells in abundance. For every million stem cells, the researchers were able to produce 30 million blood cells.

The team noted that a critical aspect of this work is the use of modified messenger RNA to direct stem cells toward particular developmental fates.

This approach makes it possible to induce cells without introducing any genetic artifacts. So this method of blood cell production is safer than other methods, according to the researchers.

“You can do it without a virus, and genome integrity is not affected,” Dr Slukvin noted.

He added that his group is still working on a method for producing hematopoietic stem cells in the lab.

“We still don’t know how to do that,” he said. “But our new approach to making blood cells will give us an opportunity to model their development in a dish and identify novel hematopoietic stem cell factors.”

Transcription factors prompt

stem cells to form endothelium

(green), then blood cells (red)

Credit: Irina Elcheva

and Akhilesh Kumar

Researchers have reported a new method for creating human blood cells in the lab, and they believe the approach is safer and more reliable than its predecessors.

The team determined how blood cells are made at the earliest stages of development; namely, 2 genetic programs are responsible for turning pluripotent stem cells into blood cells.

This discovery gave the researchers the tools to make an array of blood cells themselves, using transcription factors.

“This is the first demonstration of the production of different kinds of cells from human pluripotent stem cells using transcription factors,” said Igor Slukvin, MD, PhD, of the University of Wisconsin-Madison.

He and his colleagues described this method in Nature Communications.

During development, blood cells emerge in the aorta. There, blood cells, including hematopoietic stem cells, are generated by budding from hemogenic endothelial cells.

Dr Slukvin and his colleagues found that 2 distinct groups of transcription factors—pan-myeloid (ETV2 and GATA2) and erythro-megakaryocytic (GATA2 and TAL1)—directly convert human pluripotent stem cells into hemogenic endothelial cells.

These cells then develop into blood cells with pan-myeloid or erythro-megakaryocytic potential.

“By overexpressing just 2 transcription factors, we can, in the laboratory dish, reproduce the sequence of events we see in the embryo,” Dr Slukvin said.

Furthermore, the method could produce blood cells in abundance. For every million stem cells, the researchers were able to produce 30 million blood cells.

The team noted that a critical aspect of this work is the use of modified messenger RNA to direct stem cells toward particular developmental fates.

This approach makes it possible to induce cells without introducing any genetic artifacts. So this method of blood cell production is safer than other methods, according to the researchers.

“You can do it without a virus, and genome integrity is not affected,” Dr Slukvin noted.

He added that his group is still working on a method for producing hematopoietic stem cells in the lab.

“We still don’t know how to do that,” he said. “But our new approach to making blood cells will give us an opportunity to model their development in a dish and identify novel hematopoietic stem cell factors.”

Blood samples

Credit: Graham Colm

An immune marker may help predict which child trauma patients are likely to develop a hospital-acquired infection, and it may also provide new insight into immune response following transfusion.

In a small study, blood samples from critically ill children showed decreased production of TNF-alpha, a cytokine that’s part of the first line of defense in the innate immune system, when compared to samples from healthy control children.

In addition, TNF-alpha production was lower among children who received transfusions with older blood, compared to children who received fresher blood.

Mark W. Hall, MD, of Nationwide Children’s Hospital in Columbus, Ohio, and his colleagues reported these findings in Shock.

The researchers had collected blood samples from 21 healthy children and 76 critically injured children aged 18 years or younger. The team then exposed each sample to lipopolysaccharide (LPS), a known stimulant of the immune response. When healthy cells are exposed to LPS, it prompts the production of TNF-alpha.

When they analyzed the immune response, the researchers found that blood samples from the healthy children responded normally to LPS, producing high levels of TNF-alpha.

Samples from the patients with critical injuries all showed at least a moderate decrease in the production of TNF-alpha. But the children who went on to develop an infection showed a much more severe and persistent drop in TNF-alpha following injury.

While the findings strongly suggest that infection risk is associated with immune system function after critical injury, they don’t explain what’s causing the malfunction. Dr Hall’s team is investigating that question now.

Transfusion implications

The research also highlighted another issue that may affect the immune response in critical illness. The team found that patients who received a transfusion of blood stored for more than 2 weeks had a lower level of TNF-alpha production than kids whose transfused blood was less than 2 weeks old, regardless of the severity of their original injury.

This supports a study published by Dr Hall and his colleagues in 2012 in Transfusion. The study showed the same immunosuppressive effect in a human cell culture model.

Dr Hall plans to look into this further through his work with a multi-institutional effort called The Pediatric Critical Care Blood Research Network (BloodNet). The group is studying, among other things, what impact blood transfusions have on immune function.

“There’s a whole line of research in which we’re involved that is dedicated to understanding the effects of transfusion in critical illness,” he said. “It’s not clear yet if blood transfusions are immunosuppressive, but our work so far suggests that blood becomes more immunosuppressive the longer it sits on the shelf.”

Reversing immunosuppression

Yet another element to the study involves reversing the immunosuppression that follows critical injury or illness. The researchers took 3 blood samples in which TNF-alpha production was decreased and cultured them with GM-CSF.

Once treated, the cells began to produce normal levels of TNF-alpha—an indication that the immunosuppression had been reversed.

Dr Hall is now leading a phase 4 clinical trial of GM-CSF to reverse immunosuppression in critically injured patients aged 1 to 21 years old.

Although findings from that project won’t be ready for another year or so, the results in the Shock article seem to offer yet another weapon in physicians’ arsenal when caring for critically ill and injured children, Dr Hall said.

“We have certainly made headway in reducing preventable infections through programs such as our own Zero Hero initiative,” he noted.

“But what this paper suggests is that it’s also important to consider the patient’s immune system and how well they are able to fight off infection. We believe that critical illness- and injury-related immune suppression may be reversible with beneficial effects on clinical outcomes.”

Blood samples

Credit: Graham Colm

An immune marker may help predict which child trauma patients are likely to develop a hospital-acquired infection, and it may also provide new insight into immune response following transfusion.

In a small study, blood samples from critically ill children showed decreased production of TNF-alpha, a cytokine that’s part of the first line of defense in the innate immune system, when compared to samples from healthy control children.

In addition, TNF-alpha production was lower among children who received transfusions with older blood, compared to children who received fresher blood.

Mark W. Hall, MD, of Nationwide Children’s Hospital in Columbus, Ohio, and his colleagues reported these findings in Shock.

The researchers had collected blood samples from 21 healthy children and 76 critically injured children aged 18 years or younger. The team then exposed each sample to lipopolysaccharide (LPS), a known stimulant of the immune response. When healthy cells are exposed to LPS, it prompts the production of TNF-alpha.

When they analyzed the immune response, the researchers found that blood samples from the healthy children responded normally to LPS, producing high levels of TNF-alpha.

Samples from the patients with critical injuries all showed at least a moderate decrease in the production of TNF-alpha. But the children who went on to develop an infection showed a much more severe and persistent drop in TNF-alpha following injury.

While the findings strongly suggest that infection risk is associated with immune system function after critical injury, they don’t explain what’s causing the malfunction. Dr Hall’s team is investigating that question now.

Transfusion implications

The research also highlighted another issue that may affect the immune response in critical illness. The team found that patients who received a transfusion of blood stored for more than 2 weeks had a lower level of TNF-alpha production than kids whose transfused blood was less than 2 weeks old, regardless of the severity of their original injury.

This supports a study published by Dr Hall and his colleagues in 2012 in Transfusion. The study showed the same immunosuppressive effect in a human cell culture model.

Dr Hall plans to look into this further through his work with a multi-institutional effort called The Pediatric Critical Care Blood Research Network (BloodNet). The group is studying, among other things, what impact blood transfusions have on immune function.

“There’s a whole line of research in which we’re involved that is dedicated to understanding the effects of transfusion in critical illness,” he said. “It’s not clear yet if blood transfusions are immunosuppressive, but our work so far suggests that blood becomes more immunosuppressive the longer it sits on the shelf.”

Reversing immunosuppression

Yet another element to the study involves reversing the immunosuppression that follows critical injury or illness. The researchers took 3 blood samples in which TNF-alpha production was decreased and cultured them with GM-CSF.

Once treated, the cells began to produce normal levels of TNF-alpha—an indication that the immunosuppression had been reversed.

Dr Hall is now leading a phase 4 clinical trial of GM-CSF to reverse immunosuppression in critically injured patients aged 1 to 21 years old.

Although findings from that project won’t be ready for another year or so, the results in the Shock article seem to offer yet another weapon in physicians’ arsenal when caring for critically ill and injured children, Dr Hall said.

“We have certainly made headway in reducing preventable infections through programs such as our own Zero Hero initiative,” he noted.

“But what this paper suggests is that it’s also important to consider the patient’s immune system and how well they are able to fight off infection. We believe that critical illness- and injury-related immune suppression may be reversible with beneficial effects on clinical outcomes.”

Blood samples

Credit: Graham Colm

An immune marker may help predict which child trauma patients are likely to develop a hospital-acquired infection, and it may also provide new insight into immune response following transfusion.

In a small study, blood samples from critically ill children showed decreased production of TNF-alpha, a cytokine that’s part of the first line of defense in the innate immune system, when compared to samples from healthy control children.

In addition, TNF-alpha production was lower among children who received transfusions with older blood, compared to children who received fresher blood.

Mark W. Hall, MD, of Nationwide Children’s Hospital in Columbus, Ohio, and his colleagues reported these findings in Shock.

The researchers had collected blood samples from 21 healthy children and 76 critically injured children aged 18 years or younger. The team then exposed each sample to lipopolysaccharide (LPS), a known stimulant of the immune response. When healthy cells are exposed to LPS, it prompts the production of TNF-alpha.

When they analyzed the immune response, the researchers found that blood samples from the healthy children responded normally to LPS, producing high levels of TNF-alpha.

Samples from the patients with critical injuries all showed at least a moderate decrease in the production of TNF-alpha. But the children who went on to develop an infection showed a much more severe and persistent drop in TNF-alpha following injury.

While the findings strongly suggest that infection risk is associated with immune system function after critical injury, they don’t explain what’s causing the malfunction. Dr Hall’s team is investigating that question now.

Transfusion implications

The research also highlighted another issue that may affect the immune response in critical illness. The team found that patients who received a transfusion of blood stored for more than 2 weeks had a lower level of TNF-alpha production than kids whose transfused blood was less than 2 weeks old, regardless of the severity of their original injury.

This supports a study published by Dr Hall and his colleagues in 2012 in Transfusion. The study showed the same immunosuppressive effect in a human cell culture model.

Dr Hall plans to look into this further through his work with a multi-institutional effort called The Pediatric Critical Care Blood Research Network (BloodNet). The group is studying, among other things, what impact blood transfusions have on immune function.

“There’s a whole line of research in which we’re involved that is dedicated to understanding the effects of transfusion in critical illness,” he said. “It’s not clear yet if blood transfusions are immunosuppressive, but our work so far suggests that blood becomes more immunosuppressive the longer it sits on the shelf.”

Reversing immunosuppression

Yet another element to the study involves reversing the immunosuppression that follows critical injury or illness. The researchers took 3 blood samples in which TNF-alpha production was decreased and cultured them with GM-CSF.

Once treated, the cells began to produce normal levels of TNF-alpha—an indication that the immunosuppression had been reversed.

Dr Hall is now leading a phase 4 clinical trial of GM-CSF to reverse immunosuppression in critically injured patients aged 1 to 21 years old.

Although findings from that project won’t be ready for another year or so, the results in the Shock article seem to offer yet another weapon in physicians’ arsenal when caring for critically ill and injured children, Dr Hall said.

“We have certainly made headway in reducing preventable infections through programs such as our own Zero Hero initiative,” he noted.

“But what this paper suggests is that it’s also important to consider the patient’s immune system and how well they are able to fight off infection. We believe that critical illness- and injury-related immune suppression may be reversible with beneficial effects on clinical outcomes.”

Red blood cells

Credit: NHLBI

MANCHESTER—Preclinical research indicates that circadian disruption has severe adverse effects on red blood cells (RBCs), a finding that might possibly explain the high incidence of heart disease observed in shift workers.

The study also showed the negative effects could be reduced under hypoxic conditions. Hypoxia in combination with circadian disruption produced fresh RBCs.

And this, according to researchers, suggests blood donations might help decrease the risk of cardiovascular disease in shift workers.

This research was presented at the 2014 Annual Main Meeting of the Society for Experimental Biology (SEB). It was also published in Chronobiology International.

The researchers, led by Margit Egg, PhD, of the University of Innsbruck in Austria, set out to investigate the impact of circadian disruption on hypoxic signaling and the cardiovascular system.

The team used zebrafish, a model organism that, like humans, is active during the day. To disrupt circadian rhythms, the researchers subjected the fish to alternate short days (7 hours) and long days (21 hours), resembling shift patterns common in industry.

Results showed that circadian disruption increased the number of aged RBCs that accumulated in the blood vessels.

“Normally, there is a balance between newly produced red blood cells and old ones which are removed from the blood,” Dr Egg noted.

Old cells are less flexible and become stuck in the spleen and liver, where they are engulfed by white blood cells. Circadian disruption appears to inhibit this removal process, but the researchers are unsure why this is the case.

They do know that having large aggregates of old RBCs in the vessels increases the chance of a clot that could lead to a heart attack. This may explain why shift workers have a 30% higher risk of cardiovascular disease. In addition, the decreased functionality of the aged cells reduces the oxygen-carrying capacity of the blood.

However, the researchers also found that zebrafish were less affected by circadian disruption if they were simultaneously exposed to hypoxic conditions. This is because hypoxia stimulates the production of fresh RBCs.

The team noted that the cell signaling pathways that regulate circadian rhythms and the hypoxic response are intrinsically linked. This is based on the observation that genes activated by hypoxia, such as erythropoietin, normally show a daily rhythm of activity that becomes disturbed under hypoxic conditions.

“In zebrafish, hypoxia in combination with jetlag led to the production of fresh red blood cells, counteracting the harmful consequences of jetlag and reducing mortality by 10%,” Dr Egg noted.

“Blood donations in humans also stimulate the generation of new fresh erythrocytes. Therefore, blood donations on a regular basis might be a very simple measure to help decrease the cardiovascular risk in human shift workers.”

Dr Egg and her colleagues are currently investigating whether circadian disruption affects any other physiological processes, apart from the cardiovascular system.

Red blood cells

Credit: NHLBI

MANCHESTER—Preclinical research indicates that circadian disruption has severe adverse effects on red blood cells (RBCs), a finding that might possibly explain the high incidence of heart disease observed in shift workers.

The study also showed the negative effects could be reduced under hypoxic conditions. Hypoxia in combination with circadian disruption produced fresh RBCs.

And this, according to researchers, suggests blood donations might help decrease the risk of cardiovascular disease in shift workers.

This research was presented at the 2014 Annual Main Meeting of the Society for Experimental Biology (SEB). It was also published in Chronobiology International.

The researchers, led by Margit Egg, PhD, of the University of Innsbruck in Austria, set out to investigate the impact of circadian disruption on hypoxic signaling and the cardiovascular system.

The team used zebrafish, a model organism that, like humans, is active during the day. To disrupt circadian rhythms, the researchers subjected the fish to alternate short days (7 hours) and long days (21 hours), resembling shift patterns common in industry.

Results showed that circadian disruption increased the number of aged RBCs that accumulated in the blood vessels.

“Normally, there is a balance between newly produced red blood cells and old ones which are removed from the blood,” Dr Egg noted.

Old cells are less flexible and become stuck in the spleen and liver, where they are engulfed by white blood cells. Circadian disruption appears to inhibit this removal process, but the researchers are unsure why this is the case.

They do know that having large aggregates of old RBCs in the vessels increases the chance of a clot that could lead to a heart attack. This may explain why shift workers have a 30% higher risk of cardiovascular disease. In addition, the decreased functionality of the aged cells reduces the oxygen-carrying capacity of the blood.

However, the researchers also found that zebrafish were less affected by circadian disruption if they were simultaneously exposed to hypoxic conditions. This is because hypoxia stimulates the production of fresh RBCs.

The team noted that the cell signaling pathways that regulate circadian rhythms and the hypoxic response are intrinsically linked. This is based on the observation that genes activated by hypoxia, such as erythropoietin, normally show a daily rhythm of activity that becomes disturbed under hypoxic conditions.

“In zebrafish, hypoxia in combination with jetlag led to the production of fresh red blood cells, counteracting the harmful consequences of jetlag and reducing mortality by 10%,” Dr Egg noted.

“Blood donations in humans also stimulate the generation of new fresh erythrocytes. Therefore, blood donations on a regular basis might be a very simple measure to help decrease the cardiovascular risk in human shift workers.”

Dr Egg and her colleagues are currently investigating whether circadian disruption affects any other physiological processes, apart from the cardiovascular system.

Red blood cells

Credit: NHLBI

MANCHESTER—Preclinical research indicates that circadian disruption has severe adverse effects on red blood cells (RBCs), a finding that might possibly explain the high incidence of heart disease observed in shift workers.

The study also showed the negative effects could be reduced under hypoxic conditions. Hypoxia in combination with circadian disruption produced fresh RBCs.

And this, according to researchers, suggests blood donations might help decrease the risk of cardiovascular disease in shift workers.

This research was presented at the 2014 Annual Main Meeting of the Society for Experimental Biology (SEB). It was also published in Chronobiology International.

The researchers, led by Margit Egg, PhD, of the University of Innsbruck in Austria, set out to investigate the impact of circadian disruption on hypoxic signaling and the cardiovascular system.

The team used zebrafish, a model organism that, like humans, is active during the day. To disrupt circadian rhythms, the researchers subjected the fish to alternate short days (7 hours) and long days (21 hours), resembling shift patterns common in industry.

Results showed that circadian disruption increased the number of aged RBCs that accumulated in the blood vessels.

“Normally, there is a balance between newly produced red blood cells and old ones which are removed from the blood,” Dr Egg noted.

Old cells are less flexible and become stuck in the spleen and liver, where they are engulfed by white blood cells. Circadian disruption appears to inhibit this removal process, but the researchers are unsure why this is the case.

They do know that having large aggregates of old RBCs in the vessels increases the chance of a clot that could lead to a heart attack. This may explain why shift workers have a 30% higher risk of cardiovascular disease. In addition, the decreased functionality of the aged cells reduces the oxygen-carrying capacity of the blood.

However, the researchers also found that zebrafish were less affected by circadian disruption if they were simultaneously exposed to hypoxic conditions. This is because hypoxia stimulates the production of fresh RBCs.

The team noted that the cell signaling pathways that regulate circadian rhythms and the hypoxic response are intrinsically linked. This is based on the observation that genes activated by hypoxia, such as erythropoietin, normally show a daily rhythm of activity that becomes disturbed under hypoxic conditions.

“In zebrafish, hypoxia in combination with jetlag led to the production of fresh red blood cells, counteracting the harmful consequences of jetlag and reducing mortality by 10%,” Dr Egg noted.

“Blood donations in humans also stimulate the generation of new fresh erythrocytes. Therefore, blood donations on a regular basis might be a very simple measure to help decrease the cardiovascular risk in human shift workers.”

Dr Egg and her colleagues are currently investigating whether circadian disruption affects any other physiological processes, apart from the cardiovascular system.